Investigate the Influence of Severe Hepatic Impairment on the Pharmacokinetics of Acalabrutinib and Its Metabolite
Sponsor
Acerta Pharma BV (Industry)
Overall Status
Completed
CT.gov ID
NCT03968848
Collaborator
AstraZeneca (Industry)
16
3
2
4.5
5.3
1.2
Study Details
Study Description
Brief Summary
This study is investigate the influence of severe hepatic impairment on the pharmacokinetics of acalabrutinib and its metabolite.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
16 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date
:
Nov 12, 2018
Actual Primary Completion Date
:
Mar 13, 2019
Actual Study Completion Date
:
Mar 29, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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.
|
Outcome Measures
Primary Outcome Measures
- Plasma Acalabrutinib PK Parameters [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.]
Area Under the Concentration-Time Curve
- Maximum Plasma Acalabrutinib Concentration [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.]
Maximum Cmax
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria
-
Women must be of non childbearing status
-
Understands the study procedures in the ICF and be willing and able to comply with the protocol.
-
Willingness and ability to swallow study drug capsule.
-
Adult men or women, 18 to 75 years of age
Hepatic-Impaired Subjects Only:
-
Subject has a diagnosis of chronic, stable HI.
-
Subject's score on the Child-Pugh scale must range from 10 to 15 at screening.
Exclusion Criteria
-
History or presence of clinically significant or unstable medical or psychiatric condition or disease in the opinion of the PI.
-
Dosed in another clinical trial within 28 days before dosing of study drug and throughout the current study.
-
History or presence of drug abuse within 2 years before screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Miami | Florida | United States | 33136 |
| 2 | Research Site | Orlando | Florida | United States | 32809 |
| 3 | Research Site | Knoxville | Tennessee | United States | 37920 |
Sponsors and Collaborators
- Acerta Pharma BV
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Acerta Pharma BV
ClinicalTrials.gov Identifier:
NCT03968848
Other Study ID Numbers:
- ACE-HI-102
First Posted:
May 30, 2019
Last Update Posted:
Sep 10, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Acerta Pharma BV
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|
| Arm/Group Description | Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) |
| Period Title: Overall Study | ||
| STARTED | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Severe Hepatic Impairment | Normal Hepatic Function | Total |
|---|---|---|---|
| Arm/Group Description | Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | Total of all reporting groups |
| Overall Participants | 8 | 8 | 16 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
57.6
(7.96)
|
57.1
(4.88)
|
57.4
(6.39)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
12.5%
|
1
12.5%
|
2
12.5%
|
| Male |
7
87.5%
|
7
87.5%
|
14
87.5%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Not Hispanic or Latino |
4
50%
|
5
62.5%
|
9
56.3%
|
| Hispanic or Latino |
4
50%
|
3
37.5%
|
7
43.8%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Black or African American |
0
0%
|
1
12.5%
|
1
6.3%
|
| White |
8
100%
|
7
87.5%
|
15
93.8%
|
| Region of Enrollment (Number) [Number] | |||
| USA |
8
100%
|
8
100%
|
16
100%
|
Outcome Measures
| Title | Plasma Acalabrutinib PK Parameters |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|
| Arm/Group Description | Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) |
| Measure Participants | 8 | 8 |
| 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)
|
| Title | Maximum Plasma Acalabrutinib Concentration |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|
| Arm/Group Description | Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) |
| Measure Participants | 8 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
726.0
(56.2)
|
147.7
(116.8)
|
Adverse Events
| Time Frame | From first dose of study drug until 30 days post last dose | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Severe Hepatic Impairment | Normal Hepatic Function | ||
| Arm/Group Description | Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | ||
All Cause Mortality |
||||
| Severe Hepatic Impairment | Normal Hepatic Function | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/8 (0%) | ||
Serious Adverse Events |
||||
| Severe Hepatic Impairment | Normal Hepatic Function | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/8 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Severe Hepatic Impairment | Normal Hepatic Function | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/8 (12.5%) | 0/8 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hypokalaemia | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 |
| Hypomagnesaemia | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
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.
Results Point of Contact
| Name/Title | Global Clinical Lead |
|---|---|
| Organization | AstraZeneca Clinical Study Information Center |
| Phone | 1-877-240-9479 |
| information.center@astrazeneca.com |
Responsible Party:
Acerta Pharma BV
ClinicalTrials.gov Identifier:
NCT03968848
Other Study ID Numbers:
- ACE-HI-102
First Posted:
May 30, 2019
Last Update Posted:
Sep 10, 2021
Last Verified:
Jul 1, 2021