A Pilot Study of BMS-512148 in Subjects with Type 2 Diabetes

Study identifier:MB102-009

ClinicalTrials.gov identifier:NCT00357370

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Pilot Study of the Efficacy and Safety of BMS-512148 on Glycemic Control in Subjects with Type 2 Diabetes Treated Aggressively but not Controlled on Combination Antihyperglycemic Therapy with Metformin and/or Thiazolidinedione (TZD) and Insulin.

Medical condition

Type 2 Diabetes

Phase

Phase 2/3

Healthy volunteers

Study drug

Dapagliflozin, Placebo

Sex

All

Actual Enrollment

163

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 01 Oct 2006

Primary Completion Date: 01 Mar 2008

Study Completion Date: 01 Mar 2008

Study design

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

Verification:

Verified 01 Mar 2017 by AstraZeneca Pharmaceuticals

Collaborators

Bristol-Myers Squibb

Inclusion and exclusion criteria

Location

University Of Michigan

Ann Arbor, MI, United States, 48109

Location

Diabetes And Glandular Disease Research Associates, P.A.

San Antonio, TX, United States, 78229

Location

Mountain Diabetes And Endocrine Center

Asheville, NC, United States, 28801

Location

Endocrine Research Solutions, Inc.

Roswell, GA, United States, 30076

Location

Valley Research

Fresno, CA, United States, 93720

Location

Bernstein, Richard

Greenbrae, CA, United States, 94904

Location

Indiana University

Indianapolis, IN, United States, 46202

Location

Suny Upstate Medical University

Syracuse, NY, United States, 13210

Arms	Assigned Interventions
Experimental: Cohort 1 20 mg	Drug: Dapagliflozin Tablets, Oral, once daily, up to 12 weeks Other Name: BMS-512148
Experimental: Cohort 2 - Arm 1 10 mg	Drug: Dapagliflozin Tablets, Oral, once daily, up to 12 weeks Other Name: BMS-512148
Experimental: Cohort 2 - Arm 2 20 mg	Drug: Dapagliflozin Tablets, Oral, once daily, up to 12 weeks Other Name: BMS-512148
Placebo Comparator: Cohort 2 - Arm 3	Drug: Placebo Tablets, Oral, 0 mg, once daily, up to 12 weeks

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Of 163 participants enrolled, Of these 163 participants, 71 were randomized and received treatment. Of these 71 participants, 60 completed double-blind treatment period

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks

Participant Flow for 2 periods

Period 1: Cohort 1

	Dapagliflozin 20 mg	Placebo	Dapagliflozin 10 mg
STARTED	4	0	0
COMPLETED	4	0	0
NOT COMPLETED	0	0	0

Period 2: Cohort 2

	Dapagliflozin 20 mg	Placebo	Dapagliflozin 10 mg
STARTED	24	23	24
COMPLETED	22	16	22
NOT COMPLETED	2	7	2
Lack of Efficacy	0	2	1
Adverse Event	1	1	1
Lost to Follow-up	0	1	0
non-compliance, not met criteria, etc	1	1	0
Withdrawal by Subject	0	2	0

Baseline Characteristics

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

All randomized patients who received at least 1 dose of study medication

Reporting Groups

	Description
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks

Baseline Measures

	Dapagliflozin 20 mg	Placebo	Dapagliflozin 10 mg	Total
Number of Participants [units: Participants]	24	23	24	71
Age Continuous [units: Years] Mean ± Standard Deviation	56.1 ± 10.63	58.4 ± 6.49	55.7 ± 9.20	56.7 ± 8.92
Age, Customized [units: Participants]
Younger than 65 years	20	19	20	59
65 years or older	4	4	4	12
Gender, Customized [units: Participants]
Male	13	16	13	42
Female	11	7	11	29
Race/Ethnicity, Customized [units: Participants]
White	23	22	22	67
Back/African American	1	0	1	2
Asian	0	0	1	1
Other	0	1	0	1

Outcome Measures

1. Primary Outcome Measure: Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [ Time Frame: From Baseline to Week 12 ]

Measure Type	Primary
Measure Name	Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Measure Description	HbA1c was measured as percent of hemoglobin by a central laboratory. Data after insulin uptitration was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 6, 8, 10, and 12 in the double-blind period.
Time Frame	From Baseline to Week 12
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.
Chort 2 all randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 12 (LOCF). Note: participants in cohort 1 provided data to establish an acceptable safety and tolerability profile when dapagliflozin 20 mg was added to open-label oral antidiabetic agent plus insulin.

Reporting Groups

	Description
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks

Measured Values

	Placebo	Dapagliflozin 10 mg	Dapagliflozin 20 mg
Number of Participants Analyzed [units:participants]	19	23	23
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [units: % of hemoglobin] Mean (Standard Error)	0.09 (0.1406)	-0.61 (0.1276)	-0.69 (0.1278)

Statistical Analysis 1 for Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

Groups^[1]	Placebo, Dapagliflozin 10 mg
Non-Inferiority/Equivalence Test^[2]	No
Mean Difference (Final Values)^[5]	-0.70
Standard Error of the mean	± 0.1898
95% Confidence Interval	( -1.08 to -0.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	ANCOVA was applied. No formal statistical testing was performed to compare between treatment groups.

Statistical Analysis 2 for Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

Groups^[1]	Placebo, Dapagliflozin 20 mg
Non-Inferiority/Equivalence Test^[2]	No
Mean Difference (Final Values)^[5]	-0.78
Standard Error of the mean	± 0.1903
95% Confidence Interval	( -1.16 to -0.40 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	ANCOVA was applied. No formal statistical testing was performed to compare between treatment groups.

2. Secondary Outcome Measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [ Time Frame: From Baseline to Week 12 ]

Measure Type	Secondary
Measure Name	Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Measure Description	Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Data after insulin uptitration was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 6, 8, 10, and 12 in the double-blind period.
Time Frame	From Baseline to Week 12
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.
Chort 2 all randomized participants who received study medication and had nonmissing FPG values at baseline and Week 12 (LOCF). Note: participants in cohort 1 provided data to establish an acceptable safety and tolerability profile when dapagliflozin 20 mg was added to open-label oral antidiabetic agent plus insulin.

Reporting Groups

	Description
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks

Measured Values

	Placebo	Dapagliflozin 10 mg	Dapagliflozin 20 mg
Number of Participants Analyzed [units:participants]	22	23	23
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [units: mg/dL] Mean (Standard Error)	17.80 (8.1941)	2.36 (7.9992)	-9.64 (7.9908)

Statistical Analysis 1 for Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

Groups^[1]	Placebo, Dapagliflozin 10 mg
Non-Inferiority/Equivalence Test^[2]	No
Mean Difference (Final Values)^[5]	-15.44
Standard Error of the mean	± 11.4753
95% Confidence Interval	( -38.37 to 7.48 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	ANCOVA was applied. No formal statistical testing was performed to compare between treatment groups.

Statistical Analysis 2 for Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

Groups^[1]	Placebo, Dapagliflozin 20 mg
Non-Inferiority/Equivalence Test^[2]	No
Mean Difference (Final Values)^[5]	-27.44
Standard Error of the mean	± 11.4574
95% Confidence Interval	( -50.33 to -4.55 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	ANCOVA was applied. No formal statistical testing was performed to compare between treatment groups.

3. Secondary Outcome Measure: Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [ Time Frame: From Baseline to Week 12 ]

Measure Type	Secondary
Measure Name	Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Measure Description	Therapeutic glycemic response is defined as HbA1c <7.0%. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Time Frame	From Baseline to Week 12
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.
Chort 2 all randomized participants who received study medication and had nonmissing values at baseline and Week 12 (LOCF). Note: participants in cohort 1 provided data to establish an acceptable safety and tolerability profile when dapagliflozin 20 mg was added to open-label oral antidiabetic agent plus insulin.

Reporting Groups

	Description
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks

Measured Values

	Placebo	Dapagliflozin 10 mg	Dapagliflozin 20 mg
Number of Participants Analyzed [units:participants]	19	23	23
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [units: Participants]	1	3	1

No statistical analysis provided for Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

4. Secondary Outcome Measure: Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <=6.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [ Time Frame: From Baseline to Week 12 ]

Measure Type	Secondary
Measure Name	Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <=6.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Measure Description	Therapeutic glycemic response is defined as HbA1c <=6.5%. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Time Frame	From Baseline to Week 12
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.
Chort 2 all randomized participants who received study medication and had nonmissing values at baseline and Week 12 (LOCF). Note: participants in cohort 1 provided data to establish an acceptable safety and tolerability profile when dapagliflozin 20 mg was added to open-label oral antidiabetic agent plus insulin.

Reporting Groups

	Description
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks

Measured Values

	Placebo	Dapagliflozin 10 mg	Dapagliflozin 20 mg
Number of Participants Analyzed [units:participants]	19	23	23
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <=6.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [units: Participants]	0	1	0

No statistical analysis provided for Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <=6.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

5. Secondary Outcome Measure: Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) Decrease from Baseline >= 0.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [ Time Frame: From Baseline to Week 12 ]

Measure Type	Secondary
Measure Name	Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) Decrease from Baseline >= 0.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2
Measure Description	Therapeutic glycemic response is defined as HbA1c decrease from baseline >= 0.5% at Week 12. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Time Frame	From Baseline to Week 12
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.
Chort 2 all randomized participants who received study medication and had nonmissing values at baseline and Week 12 (LOCF). Note: participants in cohort 1 provided data to establish an acceptable safety and tolerability profile when dapagliflozin 20 mg was added to open-label oral antidiabetic agent plus insulin.

Reporting Groups

	Description
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks

Measured Values

	Placebo	Dapagliflozin 10 mg	Dapagliflozin 20 mg
Number of Participants Analyzed [units:participants]	19	23	23
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) Decrease from Baseline >= 0.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2 [units: Participants]	3	15	15

No statistical analysis provided for Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) Decrease from Baseline >= 0.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2

6. Secondary Outcome Measure: Adjusted Mean Total Daily Dose of Insulin (TDDI) Change from Baseline at Week 12 (LOCF), Including Data after Up-titration of Insulin) - Cohort 2 [ Time Frame: From Baseline to Week 12 ]

Measure Type	Secondary
Measure Name	Adjusted Mean Total Daily Dose of Insulin (TDDI) Change from Baseline at Week 12 (LOCF), Including Data after Up-titration of Insulin) - Cohort 2
Measure Description	Baseline TDDI was reduced by 50% prior to treatment, except 2 subjects. TDDI could be up-titrated according to prespecified criteria at Weeks 4, 6, 8, 10 and 12 in the double-blind period.
Time Frame	From Baseline to Week 12
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.
Chort 2 all randomized participants who received study medication and had nonmissing TDDI values at baseline and Week 12 (LOCF). Note: participants in cohort 1 provided data to establish an acceptable safety and tolerability profile when dapagliflozin 20 mg was added to open-label oral antidiabetic agent plus insulin.

Reporting Groups

	Description
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks

Measured Values

	Placebo	Dapagliflozin 10 mg	Dapagliflozin 20 mg
Number of Participants Analyzed [units:participants]	22	24	24
Adjusted Mean Total Daily Dose of Insulin (TDDI) Change from Baseline at Week 12 (LOCF), Including Data after Up-titration of Insulin) - Cohort 2 [units: units/day] Mean (Standard Error)	1.69 (2.7659)	-1.35 (2.6489)	-0.83 (2.6484)

Statistical Analysis 1 for Adjusted Mean Total Daily Dose of Insulin (TDDI) Change from Baseline at Week 12 (LOCF), Including Data after Up-titration of Insulin) - Cohort 2

Groups^[1]	Placebo, Dapagliflozin 10 mg
Non-Inferiority/Equivalence Test^[2]	No
Mean Difference (Final Values)^[5]	-3.05
Standard Error of the mean	± 3.8302
95% Confidence Interval	( -10.69 to 4.60 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	ANCOVA was applied. No formal statistical testing was performed to compare between treatment groups.

Statistical Analysis 2 for Adjusted Mean Total Daily Dose of Insulin (TDDI) Change from Baseline at Week 12 (LOCF), Including Data after Up-titration of Insulin) - Cohort 2

Groups^[1]	Placebo, Dapagliflozin 20 mg
Non-Inferiority/Equivalence Test^[2]	No
Mean Difference (Final Values)^[5]	-2.52
Standard Error of the mean	± 3.8291
95% Confidence Interval	( -10.17 to 5.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	ANCOVA was applied. No formal statistical testing was performed to compare between treatment groups.

Serious Adverse Events

Time Frame	Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Additional Description	No text entered.

Reporting Groups

	Description
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks

Serious Adverse Events

Dapagliflozin 20 mg

Placebo

Dapagliflozin 10 mg

Total, serious adverse events

# participants affected / at risk

1/24 (4.17%)

1/23 (4.35%)

0/24 (0.00%)

General disorders

NON-CARDIAC CHEST PAIN¹,^†

# participants affected / at risk

1/24 (4.17%)

0/23 (0.00%)

0/24 (0.00%)

# events

Nervous system disorders

LOSS OF CONSCIOUSNESS¹,^†

# participants affected / at risk

0/24 (0.00%)

1/23 (4.35%)

0/24 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version: 11.0

Other Adverse Events

Time Frame	Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Dapagliflozin 20 mg	Tablets, oral, once daily for 12 weeks
Placebo	Tablets, oral, once daily for 12 weeks
Dapagliflozin 10 mg	Tablets, oral, once daily for 12 weeks

Other Adverse Events

Dapagliflozin 20 mg

Placebo

Dapagliflozin 10 mg

Total, other (not including serious) adverse events

# participants affected / at risk

13/24 (54.17%)

12/23 (52.17%)

12/24 (50.00%)

Gastrointestinal disorders

NAUSEA¹,^†

# participants affected / at risk

3/24 (12.50%)

1/23 (4.35%)

1/24 (4.17%)

# events

Renal and urinary disorders

POLLAKIURIA¹,^†

# participants affected / at risk

3/24 (12.50%)

4/23 (17.39%)

2/24 (8.33%)

# events

Gastrointestinal disorders

VOMITING¹,^†

# participants affected / at risk

3/24 (12.50%)

0/23 (0.00%)

0/24 (0.00%)

# events

Infections and infestations

VULVOVAGINAL MYCOTIC INFECTION¹,^†

# participants affected / at risk

3/24 (12.50%)

0/23 (0.00%)

0/24 (0.00%)

# events

Psychiatric disorders

ANXIETY¹,^†

# participants affected / at risk

2/24 (8.33%)

0/23 (0.00%)

0/24 (0.00%)

# events

Musculoskeletal and connective tissue disorders

BACK PAIN¹,^†

# participants affected / at risk

2/24 (8.33%)

2/23 (8.70%)

3/24 (12.50%)

# events

Gastrointestinal disorders

DRY MOUTH¹,^†

# participants affected / at risk

2/24 (8.33%)

0/23 (0.00%)

0/24 (0.00%)

# events

Infections and infestations

NASOPHARYNGITIS¹,^†

# participants affected / at risk

2/24 (8.33%)

2/23 (8.70%)

2/24 (8.33%)

# events

General disorders

OEDEMA PERIPHERAL¹,^†

# participants affected / at risk

2/24 (8.33%)

0/23 (0.00%)

0/24 (0.00%)

# events

Gastrointestinal disorders

ABDOMINAL PAIN UPPER¹,^†

# participants affected / at risk

1/24 (4.17%)

2/23 (8.70%)

0/24 (0.00%)

# events

General disorders

FATIGUE¹,^†

# participants affected / at risk

1/24 (4.17%)

0/23 (0.00%)

2/24 (8.33%)

# events

Infections and infestations

INFLUENZA¹,^†

# participants affected / at risk

1/24 (4.17%)

2/23 (8.70%)

1/24 (4.17%)

# events

Musculoskeletal and connective tissue disorders

PAIN IN EXTREMITY¹,^†

# participants affected / at risk

1/24 (4.17%)

1/23 (4.35%)

2/24 (8.33%)

# events

General disorders

THIRST¹,^†

# participants affected / at risk

1/24 (4.17%)

1/23 (4.35%)

2/24 (8.33%)

# events

Infections and infestations

UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

1/24 (4.17%)

2/23 (8.70%)

2/24 (8.33%)

# events

Nervous system disorders

HEADACHE¹,^†

# participants affected / at risk

0/24 (0.00%)

2/23 (8.70%)

3/24 (12.50%)

# events

Respiratory, thoracic and mediastinal disorders

PHARYNGOLARYNGEAL PAIN¹,^†

# participants affected / at risk

0/24 (0.00%)

0/23 (0.00%)

2/24 (8.33%)

# events

Injury, poisoning and procedural complications

PROCEDURAL PAIN¹,^†

# participants affected / at risk

0/24 (0.00%)

2/23 (8.70%)

0/24 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version: 11.0

Certain Agreements

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

There is NOT 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.

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
Cohort 1 data provided information on insulin dose adjustment (n=4).

Results Point of Contact

Name/Title:	Anna Maria Langkilde
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

First line of email MUST contain NCT# & Site#. Only trial are recruiting have contact information at this time.

Investigators

Principal Investigator

Bristol-Myers Squibb

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

University Of Michigan

Diabetes And Glandular Disease Research Associates, P.A.

Mountain Diabetes And Endocrine Center

Endocrine Research Solutions, Inc.

Valley Research

Bernstein, Richard

Indiana University

Suny Upstate Medical University

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm

Trial Results Summaries