To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects with Stable Coronary Artery Disease

Study identifier:D5780C00002

ClinicalTrials.gov identifier:NCT02601560

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 2a Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single- Ascending Doses of MEDI6012 in Subjects with Stable Coronary Artery Disease

Medical condition

Coronary artery disease

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

40 Years - 75 Years

Date

Study Start Date: 03 Dec 2015

Primary Completion Date: 20 Aug 2016

Study Completion Date: 03 Nov 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Sequential Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2018 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Cincinnati, OH, United States, 45227

Location

Research Site

San Antonio, TX, United States, 78229

Location

Research Site

Jacksonville, FL, United States, 32216

Location

Research Site

Anniston, AL, United States, 36207

Location

Research Site

Durham, NC, United States, 27710

Location

Research Site

Raleigh, NC, United States, 27612

Location

Research Site

Port Orange, FL, United States, 32127

Location

Research Site

Falls Church, VA, United States, 22042

Arms	Assigned Interventions
Experimental: MEDI6012 24 mg IV Participants received a single IV dose of 24 mg MEDI6012 on Day 1.	Biological/Vaccine: MEDI6012 Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.
Experimental: MEDI6012 80 mg IV Participants received a single IV dose of 80 mg MEDI6012 on Day 1.	Biological/Vaccine: MEDI6012 Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.
Experimental: MEDI6012 240 mg IV Participants received a single IV dose of 240 mg MEDI6012 on Day 1.	Biological/Vaccine: MEDI6012 Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.
Experimental: MEDI6012 800 mg IV Participants received a single IV dose of 800 mg MEDI6012 on Day 1.	Biological/Vaccine: MEDI6012 Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.
Experimental: MEDI6012 80 mg SC Participants received a single SC dose of 80 mg MEDI6012 on Day 1.	Biological/Vaccine: MEDI6012 Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.
Placebo Comparator: Placebo Intravenous (IV) Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.	Biological/Vaccine: Placebo IV Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
Experimental: MEDI6012 600 mg SC Participants received a single SC dose of 600 mg MEDI6012 on Day 1.	Biological/Vaccine: MEDI6012 Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.
Placebo Comparator: Placebo Subcutaneous (SC) Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.	Biological/Vaccine: Placebo SC Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 230 participants were screened in the study from 07-Dec-2015 to 13-Jan-2017 at 8 sites in the United States of America.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of 230 participants, 182 participants were considered screen failures. The remaining 48 participants were randomized to receive the study drug. The 1600 mg dose was omitted based on a greater than expected pharmacodynamics effects at lower doses.

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Participant Flow: Overall Study

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
STARTED	8	6	6	6	6	4	6	6
COMPLETED	8	6	6	6	6	4	5	6
NOT COMPLETED	0	0	0	0	0	0	1	0
Unspecified	0	0	0	0	0	0	1	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

As-treated Population: All participants who received any amount of study drug were included in this population.

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Baseline Measures

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC	Total
Number of Participants [units: Participants]	8	6	6	6	6	4	6	6	48
Age Continuous [units: Years] Mean ± Standard Deviation	62.8 ± 6.5	59.8 ± 7.0	60.0 ± 6.4	63.5 ± 5.4	65.8 ± 8.2	62.0 ± 9.3	71.3 ± 3.4	66.5 ± 4.7	64.0 ± 6.9
Gender, Male/Female [units: ]
Female	1	0	3	2	1	1	0	1	39
Male	7	6	3	4	5	3	6	5	9

Outcome Measures

1. Primary Outcome Measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Baseline (Day 1) up to Day 57 ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Measure Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are the events between first dose of study drug and up to 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Baseline (Day 1) up to Day 57
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated Population: All participants who received any amount of study drug were included in this population.

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [units: Participants]
TEAEs	3	2	5	2	4	2	3	4
TESAEs	0	0	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

2. Primary Outcome Measure: Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations [ Time Frame: Baseline (Day 1) up to Day 57 ]

Measure Type	Primary
Measure Name	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations
Measure Description	TEAEs observed in participants with clinically significant ECG abnormalities were assessed. TEAEs are the events between first dose of study drug and up to 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Baseline (Day 1) up to Day 57
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated Population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations [units: Participants]	0	0	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations

3. Primary Outcome Measure: Number of Participants With TEAEs Related to Vital Sign Parameters [ Time Frame: Baseline (Day 1) up to Day 57 ]

Measure Type	Primary
Measure Name	Number of Participants With TEAEs Related to Vital Sign Parameters
Measure Description	TEAEs observed in participants with clinically significant vital signs abnormalities were assessed. Vital signs parameters included blood pressure, respiration rate, pulse, pulse oximetry, and body temperature.
Time Frame	Baseline (Day 1) up to Day 57
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated Population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Number of Participants With TEAEs Related to Vital Sign Parameters [units: Participants]	0	0	0	0	0	0	0	0

No statistical analysis provided for Number of Participants With TEAEs Related to Vital Sign Parameters

4. Primary Outcome Measure: Number of Participants With TEAEs Related to Clinical Laboratory Evaluations [ Time Frame: Baseline (Day 1) up to Day 57 ]

Measure Type	Primary
Measure Name	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations
Measure Description	An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Time Frame	Baseline (Day 1) up to Day 57
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated Population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Number of Participants With TEAEs Related to Clinical Laboratory Evaluations [units: Participants]	0	0	0	0	0	0	1	0

No statistical analysis provided for Number of Participants With TEAEs Related to Clinical Laboratory Evaluations

5. Primary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C) [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion, 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Primary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of HDL-C.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion, 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated Population.

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C) [units: milligrams per deciliter (mg/dL)] Mean (Standard Deviation)	-49.1 (120.0)	728.3 (334.2)	1639.9 (631.7)	3035.0 (439.1)	5318.3 (1674.3)	-113.5 (289.4)	422.4 (395.7)	2844.7 (1219.1)

Statistical Analysis 1 for Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)

Groups^[1]	Placebo Intravenous (IV), MEDI6012 24 milligram (mg) IV
Method^[3]	ANCOVA
P-Value^[4]	0.095

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)

Groups^[1]	Placebo Intravenous (IV), MEDI6012 80 mg IV
Method^[3]	ANCOVA
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 3 for Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)

Groups^[1]	Placebo Intravenous (IV), MEDI6012 240 mg IV
Method^[3]	ANCOVA
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 4 for Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)

Groups^[1]	Placebo Intravenous (IV), MEDI6012 800 mg IV
Method^[3]	ANCOVA
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 5 for Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)

Groups^[1]	Placebo Subcutaneous (SC), MEDI6012 600 mg SC
Method^[3]	ANCOVA
P-Value^[4]	0.440

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 6 for Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (hrs) (AUC [0-96 hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)

Groups^[1]	Placebo Subcutaneous (SC), MEDI6012 80 mg SC
Method^[3]	ANCOVA
P-Value^[4]	<0.001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

6. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Total Cholesterol [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Total Cholesterol
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of total cholesterol.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Total Cholesterol [units: mg/dL] Mean (Standard Deviation)	13.8 (954.1)	-164.9 (1301.5)	1925.7 (913.3)	3639.2 (667.6)	6990.3 (1764.0)	82.3 (983.4)	240.9 (494.2)	3156.8 (1476.5)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Total Cholesterol

7. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Free Cholesterol [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Free Cholesterol
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of free cholesterol.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Free Cholesterol [units: mg/dL] Mean (Standard Deviation)	38.4 (265.4)	-197.7 (338.2)	38.9 (346.8)	110.0 (133.9)	434.6 (541.7)	172.5 (76.6)	-61.5 (206.6)	-205.4 (324.5)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Free Cholesterol

8. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Cholesteryl Ester [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Cholesteryl Ester
Measure Description	The AUC(0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of cholesteryl ester.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Cholesteryl Ester [units: mg/dL] Mean (Standard Deviation)	-24.6 (776.0)	32.8 (992.6)	1886.8 (722.8)	3529.2 (628.3)	6555.7 (1674.0)	-90.2 (965.4)	302.4 (428.4)	3362.3 (1340.5)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Cholesteryl Ester

9. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Cholesteryl Ester [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Cholesteryl Ester
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of high density lipoprotein cholesteryl ester.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Cholesteryl Ester [units: mg/dL] Mean (Standard Deviation)	-50.3 (108.9)	668.4 (263.3)	1460.7 (584.0)	2778.0 (416.7)	4886.0 (1459.7)	-132.6 (253.1)	392.7 (350.3)	2672.5 (1115.7)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Cholesteryl Ester

10. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesterol [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesterol
Measure Description	The AUC(0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein cholesterol.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesterol [units: mg/dL] Mean (Standard Deviation)	63.0 (906.4)	-893.2 (1316.0)	285.8 (1051.8)	604.2 (659.1)	1672.0 (1413.4)	195.8 (809.9)	-181.5 (385.1)	312.2 (642.4)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesterol

11. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Unesterified Cholesterol [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Unesterified Cholesterol
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of high density lipoprotein unesterified cholesterol.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Unesterified Cholesterol [units: mg/dL] Mean (Standard Deviation)	1.2 (38.0)	59.9 (78.9)	179.2 (116.5)	248.4 (37.6)	417.1 (256.1)	19.1 (46.6)	29.7 (77.5)	172.2 (156.6)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for High-Density Lipoprotein Unesterified Cholesterol

12. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesteryl Ester [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesteryl Ester
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein cholesteryl ester.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesteryl Ester [units: mg/dL] Mean (Standard Deviation)	25.8 (748.1)	-635.6 (984.0)	426.1 (723.0)	741.6 (590.5)	1649.5 (1007.5)	42.4 (791.6)	-90.3 (390.6)	689.8 (634.5)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Cholesteryl Ester

13. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Unesterified Cholesterol [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Unesterified Cholesterol
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein unesterified cholesterol.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Unesterified Cholesterol [units: mg/dL] Mean (Standard Deviation)	37.2 (241.2)	-257.6 (351.8)	-140.3 (354.7)	-132.2 (139.9)	27.8 (609.9)	153.4 (72.9)	-91.2 (155.2)	-377.6 (280.7)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Non-High Density Lipoprotein Unesterified Cholesterol

14. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Low Density Lipoprotein-Cholesterol (Direct) [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Low Density Lipoprotein-Cholesterol (Direct)
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of low density lipoprotein cholesterol (direct).
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Low Density Lipoprotein-Cholesterol (Direct) [units: mg/dL] Mean (Standard Deviation)	182.1 (600.9)	-473.0 (1096.4)	83.2 (762.0)	987.2 (453.8)	1812.8 (1081.8)	-101.6 (854.2)	-61.7 (438.1)	996.1 (803.5)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) for Low Density Lipoprotein-Cholesterol (Direct)

15. Secondary Outcome Measure: Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) Post Dose for Apolipoprotein B [ Time Frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) Post Dose for Apolipoprotein B
Measure Description	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of apolipoprotein B.
Time Frame	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) Post Dose for Apolipoprotein B [units: mg/dL] Mean (Standard Deviation)	220.7 (524.7)	-795.5 (695.5)	-636.7 (682.6)	-649.5 (208.6)	-537.1 (706.2)	97.4 (483.2)	-309.0 (270.5)	-219.0 (630.7)

No statistical analysis provided for Baseline-adjusted Area Under the Curve From Time 0 to 96 hrs (AUC [0-96 hrs]) Post Dose for Apolipoprotein B

16. Secondary Outcome Measure: Change From Baseline in Serum Concentration of Pre beta 1-High Density Lipoprotein at Day 29 [ Time Frame: Baseline (Day 1) and Day 29 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Serum Concentration of Pre beta 1-High Density Lipoprotein at Day 29
Measure Description	The change from baseline in serum concentration of pre beta 1-high density lipoprotein was estimated.
Time Frame	Baseline (Day 1) and Day 29
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population.

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Change From Baseline in Serum Concentration of Pre beta 1-High Density Lipoprotein at Day 29 [units: mg/dL] Mean (Standard Deviation)
Baseline (Day 1)	3.68 (2.24)	1.75 (0.37)	2.08 (1.19)	2.53 (1.80)	4.85 (4.01)	3.90 (NA)^[1]	3.38 (1.48)	1.67 (0.46)
Change at Day 29	-0.20 (1.27)	-0.02 (0.84)	0.13 (0.32)	0.40 (0.62)	-1.12 (3.21)	-1.10 (NA)^[1]	1.33 (1.44)	0.10 (0.60)

No statistical analysis provided for Change From Baseline in Serum Concentration of Pre beta 1-High Density Lipoprotein at Day 29

17. Secondary Outcome Measure: Change From Baseline in Serum Concentration of Lecithin-Cholesterol Acyltransferase (LCAT) at Day 57 [ Time Frame: Baseline (Day 1) and Day 57 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Serum Concentration of Lecithin-Cholesterol Acyltransferase (LCAT) at Day 57
Measure Description	The change from baseline in serum concentration of lecithin-cholesterol acyltransferase was estimated.
Time Frame	Baseline (Day 1) and Day 57
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) population: All participants in the as-treated population who had atleast one detectable LCAT serum concentration measurement.

Reporting Groups

	Description
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	6	6	6	6	5	6
Change From Baseline in Serum Concentration of Lecithin-Cholesterol Acyltransferase (LCAT) at Day 57 [units: mcg/mL] Mean (Standard Deviation)
Baseline (Day 1)	1250.0 (0.0)	1250.0 (0.0)	1250.0 (0.0)	1250.0 (0.0)	1250.0 (0.0)	1250.0 (0.0)
Change at Day 57	0.0 (NA)^[1]			0.0 (0.0)	0.0 (NA)^[1]

No statistical analysis provided for Change From Baseline in Serum Concentration of Lecithin-Cholesterol Acyltransferase (LCAT) at Day 57

18. Secondary Outcome Measure: Maximum Observed Serum Concentration (Cmax) of MEDI6012 [ Time Frame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Maximum Observed Serum Concentration (Cmax) of MEDI6012
Measure Description	The first occurrence of the maximum observed plasma concentration of MEDI6012 determined directly from the raw concentration time data.
Time Frame	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (<2.5 mcg/mL).

Reporting Groups

	Description
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Maximum Observed Serum Concentration (Cmax) of MEDI6012 [units: micrograms/milliliter (mcg/mL)] Mean (Standard Deviation)	5.02 (2.25)	20.2 (4.15)	73.5 (9.40)	229 (55.4)	22.8 (9.75)

No statistical analysis provided for Maximum Observed Serum Concentration (Cmax) of MEDI6012

19. Secondary Outcome Measure: Time to Reach Concentration Maximum (Tmax) of MEDI6012 [ Time Frame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Time to Reach Concentration Maximum (Tmax) of MEDI6012
Measure Description	The time at which Cmax of MEDI6012 was observed determined directly from raw concentration time data.
Time Frame	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (<2.5 mcg/mL).

Reporting Groups

	Description
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Time to Reach Concentration Maximum (Tmax) of MEDI6012 [units: hrs] Median (Full Range)	1.00 (1.00 to 1.00)	1.00 (1.00 to 1.50)	1.00 (1.00 to 2.00)	1.00 (1.00 to 1.50)	48.0 (48.0 to 72.0)

No statistical analysis provided for Time to Reach Concentration Maximum (Tmax) of MEDI6012

20. Secondary Outcome Measure: Area Under the Concentration Time Curve From 0 to 168 hrs (AUC [0-168]) of MEDI6012 [ Time Frame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Area Under the Concentration Time Curve From 0 to 168 hrs (AUC [0-168]) of MEDI6012
Measure Description	The area under the concentration-time curve from 0 to 168 hrs of MEDI6012.
Time Frame	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (<2.5 mcg/mL).

Reporting Groups

	Description
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Area Under the Concentration Time Curve From 0 to 168 hrs (AUC [0-168]) of MEDI6012 [units: mcg*hr/mL] Mean (Standard Deviation)	137 (55.0)	805 (265)	2760 (249)	8470 (2000)	2460 (824)

No statistical analysis provided for Area Under the Concentration Time Curve From 0 to 168 hrs (AUC [0-168]) of MEDI6012

21. Secondary Outcome Measure: Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012 [ Time Frame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012
Measure Description	Area under the plasma concentration time-curve from zero to the last measured concentration (AUC [0-last]) of MEDI6012.
Time Frame	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (<2.5 mcg/mL).

Reporting Groups

	Description
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012 [units: mcg*hr/mL] Mean (Standard Deviation)	46.8 (42.7)	683 (267)	2760 (249)	9020 (2760)	2460 (824)

No statistical analysis provided for Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012

22. Secondary Outcome Measure: Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012 [ Time Frame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012
Measure Description	The area under the concentration-time curve to infinite time of MEDI6012.
Time Frame	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (<2.5 mcg/mL).

Reporting Groups

	Description
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012 [units: mcg*hr/mL] Mean (Standard Deviation)	137 (56.1)	887 (308)	3030 (298)	9510 (2720)	3560 (732)

No statistical analysis provided for Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012

23. Secondary Outcome Measure: Elimination Half Life (t1/2) of MEDI6012 [ Time Frame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only) ]

Measure Type	Secondary
Measure Name	Elimination Half Life (t1/2) of MEDI6012
Measure Description	The t1/2 is the time measured for the plasma concentration to decrease by one half.
Time Frame	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (<2.5 mcg/mL).

Reporting Groups

	Description
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Elimination Half Life (t1/2) of MEDI6012 [units: hrs] Mean (Standard Deviation)	17.6 (5.47)	46.9 (17.6)	45.7 (3.67)	55.4 (14.2)	89.5 (46.7)

No statistical analysis provided for Elimination Half Life (t1/2) of MEDI6012

24. Secondary Outcome Measure: Number of Participants with Positive Anti-Drug Antibodies for MEDI6012 [ Time Frame: Day 1 (pre-dose), 15, 29 and 57 ]

Measure Type	Secondary
Measure Name	Number of Participants with Positive Anti-Drug Antibodies for MEDI6012
Measure Description	Participants were tested for immunogenicity to MEDI6012. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of MEDI6012 to its target.
Time Frame	Day 1 (pre-dose), 15, 29 and 57
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population: All participants in the as-treated population with at least one serum sample available for immunogenicity testing.

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Measured Values

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Number of Participants Analyzed [units:participants]	8	6	6	6	6	4	6	6
Number of Participants with Positive Anti-Drug Antibodies for MEDI6012 [units: Participants]
Day 1 (predose)	0	0	0	0	0	0	0	0
Day 15	0	0	0	0	0	0	0	1
Day 29	0	0	0	0	1	0	1	0
Day 57		0			2		1

No statistical analysis provided for Number of Participants with Positive Anti-Drug Antibodies for MEDI6012

Serious Adverse Events

Time Frame	Adverse events were collected from baseline (Day 1) throughout the treatment period and including the follow-up period (up to Day 57).
Additional Description	No text entered.

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Serious Adverse Events

	Placebo Intravenous (IV)	MEDI6012 24 milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC
Total, serious adverse events
# participants affected / at risk	0/8 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/4 (0.00%)	0/6 (0.00%)	0/6 (0.00%)

Other Adverse Events

Time Frame	Adverse events were collected from baseline (Day 1) throughout the treatment period and including the follow-up period (up to Day 57).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Placebo Intravenous (IV)	Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 24 milligram (mg) IV	Participants received a single IV dose of 24 mg MEDI6012 on Day 1.
MEDI6012 80 mg IV	Participants received a single IV dose of 80 mg MEDI6012 on Day 1.
MEDI6012 240 mg IV	Participants received a single IV dose of 240 mg MEDI6012 on Day 1.
MEDI6012 800 mg IV	Participants received a single IV dose of 800 mg MEDI6012 on Day 1.
Placebo Subcutaneous (SC)	Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.
MEDI6012 80 mg SC	Participants received a single SC dose of 80 mg MEDI6012 on Day 1.
MEDI6012 600 mg SC	Participants received a single SC dose of 600 mg MEDI6012 on Day 1.

Other Adverse Events

Placebo Intravenous (IV)

MEDI6012 24 milligram (mg) IV

MEDI6012 80 mg IV

MEDI6012 240 mg IV

MEDI6012 800 mg IV

Placebo Subcutaneous (SC)

MEDI6012 80 mg SC

MEDI6012 600 mg SC

Total, other (not including serious) adverse events

# participants affected / at risk

3/8 (37.50%)

2/6 (33.33%)

5/6 (83.33%)

2/6 (33.33%)

4/6 (66.67%)

2/4 (50.00%)

3/6 (50.00%)

4/6 (66.67%)

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

# events

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Eye disorders

Diplopia¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Gastrointestinal disorders

Abdominal discomfort¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/8 (12.50%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/8 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

2/4 (50.00%)

0/6 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

# events

General disorders

Infusion site bruising¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

General disorders

Infusion site reaction¹,^†

# participants affected / at risk

0/8 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

General disorders

Injection site bruising¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

# events

General disorders

Injection site erythema¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

2/6 (33.33%)

# events

General disorders

Injection site haemorrhage¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

# events

General disorders

Injection site pain¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

# events

General disorders

Injection site reaction¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

2/6 (33.33%)

1/6 (16.67%)

# events

General disorders

Medical device site irritation¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Investigations

High density lipoprotein decreased¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Investigations

Respiratory rate increased¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/8 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Limb discomfort¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Nervous system disorders

Burning sensation¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

2/6 (33.33%)

# events

Nervous system disorders

Lethargy¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Nervous system disorders

Migraine¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/4 (25.00%)

0/6 (0.00%)

# events

Nervous system disorders

Presyncope¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

# events

Nervous system disorders

Slow speech¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

# events

Renal and urinary disorders

Microalbuminuria¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

# events

Reproductive system and breast disorders

Benign prostatic hyperplasia¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/4 (0.00%)

0/6 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis allergic¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis contact¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Skin and subcutaneous tissue disorders

Ecchymosis¹,^†

# participants affected / at risk

1/8 (12.50%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

1/8 (12.50%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/4 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/4 (0.00%)

0/6 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Richard George, MD, Director, Clinical Development
Organization:	MedImmune, LLC
Phone	+1-301-398-5681
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries