Investigate the Influence of Severe Hepatic Impairment on the Pharmacokinetics of Acalabrutinib and its Metabolite

Study identifier:ACE-HI-102

ClinicalTrials.gov identifier:NCT03968848

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1, Open-Label, Single-Dose Study to Investigate the Influence of Severe Hepatic Impairment on the Pharmacokinetics of Acalabrutinib and its Metabolite (ACP-5862)

Medical condition

Hepatic Impairment, Hepatic insufficiency, Healthy subjects

Phase

Phase 1

Healthy volunteers

Yes

Study drug

acalabrutinib

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 12 Nov 2018

Primary Completion Date: 13 Mar 2019

Study Completion Date: 29 Mar 2019

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2021 by Acerta Pharma BV

Collaborators

AstraZeneca

Inclusion and exclusion criteria

Location

Research Site

Miami, Florida, United States, 33136

Location

Research Site

Orlando, Florida, United States, 32809

Location

Research Site

Knoxville, Tennessee, United States, 37920

Arms	Assigned Interventions
Experimental: Subjects with Severe Hepatic Impairment Subjects with severe hepatic impairment (score of 10 to 15 on the Child-Pugh scale) will be administrated a 50-mg single oral dose of acalabrutinib.	Drug: acalabrutinib A 50-mg single oral dose of acalabrutinib will be administered.
Experimental: Matched-Control Subjects Subjects with normal hepatic function will be administrated a 50-mg single oral dose of acalabrutinib.	Drug: acalabrutinib A 50-mg single oral dose of acalabrutinib will be administered.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

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
Severe hepatic impairment	Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
Normal hepatic function	Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)

Participant Flow: Overall Study

	Severe hepatic impairment	Normal hepatic function
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

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

Reporting Groups

	Description
Severe hepatic impairment	Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
Normal hepatic function	Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)

Baseline Measures

	Severe hepatic impairment	Normal hepatic function	Total
Number of Participants [units: Participants]	8	8	16
Age Continuous [units: Years] Mean ± Standard Deviation	57.6 ± 7.96	57.1 ± 4.88	57.4 ± 6.39
Sex: Female, Male [units: Participants]
Male	7	7	14
Female	1	1	2
Ethnicity (NIH/OMB) [units: Participants]
Not Hispanic or Latino	4	5	9
Hispanic or Latino	4	3	7
Race (NIH/OMB) [units: Participants]
Black or African American	0	1	1
White	8	7	15
Region of Enrollment [units: Participants] USA	8	8	16

Outcome Measures

1. Primary Outcome Measure: Plasma Acalabrutinib PK parameters [ Time Frame: Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose. ]

Measure Type	Primary
Measure Name	Plasma Acalabrutinib PK parameters
Measure Description	Area Under the Concentration-Time Curve
Time Frame	Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose.
Safety Issue?

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.

Reporting Groups

	Description
Severe Hepatic Impairment	Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
Normal Hepatic Function	Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)

Measured Values

	Severe Hepatic Impairment	Normal Hepatic Function
Number of Participants Analyzed [units:participants]	8	8
Plasma Acalabrutinib PK parameters [units: ng*hr/mL] Geometric Mean (Geometric Coefficient of Variation)
AUC0-24	1167 (53.6%)	226.1 (55.3%)
AUC0-last	1161 (53.9%)	220.0 (57.3%)
AUC0-inf	1169 (53.8%)	226.5 (55.1%)

No statistical analysis provided for Plasma Acalabrutinib PK parameters

2. Primary Outcome Measure: Maximum Plasma Acalabrutinib Concentration [ Time Frame: Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose. ]

Measure Type	Primary
Measure Name	Maximum Plasma Acalabrutinib Concentration
Measure Description	Maximum Cmax
Time Frame	Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose.
Safety Issue?

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.

Reporting Groups

	Description
Severe Hepatic Impairment	Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
Normal Hepatic Function	Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)

Measured Values

	Severe Hepatic Impairment	Normal Hepatic Function
Number of Participants Analyzed [units:participants]	8	8
Maximum Plasma Acalabrutinib Concentration [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	726.0 (56.2%)	147.7 (116.8%)

No statistical analysis provided for Maximum Plasma Acalabrutinib Concentration

Serious Adverse Events

Time Frame	From first dose of study drug until 30 days post last dose
Additional Description	No text entered.

Reporting Groups

	Description
Severe hepatic impairment	Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
Normal hepatic function	Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)

Serious Adverse Events

	Severe hepatic impairment	Normal hepatic function
Total, serious adverse events
# participants affected / at risk	0/8 (0.00%)	0/8 (0.00%)

Other Adverse Events

Time Frame	From first dose of study drug until 30 days post last dose
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Severe hepatic impairment	Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
Normal hepatic function	Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)

Other Adverse Events

Severe hepatic impairment

Normal hepatic function

Total, other (not including serious) adverse events

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

1/8 (12.50%)

0/8 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 21.1

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
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical Study Information Center
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

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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

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