A Study to Evaluate the Effect of Hepatic Insufficiency on the Pharmacokinetics (PK) of ACP-196

NCT04867941 | Completed Phase 1 FDA Drug

• 1 other identifier: ACE-HI-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

The study will evaluate the influence of hepatic insufficiency on the PK of ACP-196.

Conditions

Hepatic Insufficiency

Keywords

ACP-196; Healthy participants; Mild hepatic impairment; Moderate hepatic impairment; Severe hepatic impairment; Pharmacokinetics; PK; Safety

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms

• Maximum Observed Plasma Concentration (Cmax) of ACP-196

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms

Secondary Outcomes (13)

• Area Under the Plasma Concentration-time Curve From Time 0 To Time of Last Measurable Concentration (AUC0-last) of ACP-196

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms

• Area Under the Plasma Concentration-time Curve From Time 0 To 24 Hours (AUC0-24) of ACP-196

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms

• Percent of AUC0inf Extrapolated (AUC%extrap) of ACP-196

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms

• Time of the Maximum Measured Plasma Concentration (Tmax) of ACP-196

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms

• Time of the Last Measurable Plasma Concentration (Tlast) of ACP-196

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms

Study Arms (4)

Part1: Mild hepatic insufficiency

EXPERIMENTAL

Participants with mild hepatic insufficiency will receive a single oral dose of 50 mg ACP-196 (2 x 25 mg capsules) on Day 1 of the study.

Drug: ACP-196

Part 1: Moderate hepatic insufficiency

EXPERIMENTAL

Participants with moderate hepatic insufficiency will receive a single oral dose of 50 mg ACP-196 (2 x 25 mg capsules) on Day 1 of the study.

Drug: ACP-196

Part 1: Normal hepatic function

EXPERIMENTAL

Participants with normal hepatic function will receive a single oral dose of 50 mgACP-196 (2 x 25 mg capsules) on Day 1 of the study.

Drug: ACP-196

Part 2: Severe hepatic insufficiency

EXPERIMENTAL

Participants with sever hepatic insufficiency will receive a single oral dose of 50 mg ACP-196 (2 x 25 mg capsules) on Day 1 of the study.

Drug: ACP-196

Interventions

ACP-196 DRUG

All study participants will receive a single oral dose of 50 mg ACP-196 (2 x 25 mg capsules) on Day 1 of the study.

Also known as: Acalabrutinib

Part 1: Moderate hepatic insufficiency; Part 1: Normal hepatic function; Part 2: Severe hepatic insufficiency; Part1: Mild hepatic insufficiency

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Participants:
• Continuous non-smokers or smokers (of fewer than 20 cigarettes/day or the equivalent). Participants must agree to consume no more than 10 cigarettes or equivalent/day from 24 hours before dosing and throughout the period of sample collection.
• Women participants must be of non-child bearing status and must have negative serum pregnancy test.
• Men of reproductible potential must be willing to abstain from heterosexual intercourse or refrain from sperm donation or use contraception during the study and through 90 days after the last dose of study drug.
• Hepatic impaired participants:
• Body mass index (BMI) \>= 19 and \<= 40 kg/m\^2, at screening.
• Have medical history, physical examination, vital signs, 12-lead ECGs, and laboratory safety tests consistent with a diagnosis of hepatic impairment, but is otherwise judged to be in good health as determined by the principal investigator (PI).
• Participant has a diagnosis of chronic (\> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology.
• Part 1 only: Mild - Participant's score on the Child-Pugh scale must range from 5 to 6 (mild hepatic insufficiency) at screening. Moderate - Participant's score on the Child-Pugh scale must range from 7 to 9 (moderate hepatic insufficiency) at screening. For participants who have compensated hepatic insufficiency while on medical therapy, they should be classified by their pretreatment parameters.
• Part 2 only: Severe - Participant's score on the Child-Pugh scale must range from 10 to 15 (severe hepatic insufficiency) at screening. For participant's who have compensated hepatic insufficiency while on medical therapy, they should be classified by their pretreatment parameters.
• Healthy control participants only:
• BMI \>= 19 and \<= 40 kg/m\^2 at screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the PI. Liver function tests, and serum bilirubin, must be \<= the upper limit of normal at screening.

You may not qualify if:

• All participants:
• History or presence of clinically significant or unstable medical or psychiatric condition or disease in the opinion of the PI.
• Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• Any clinically significant condition that may affect ACP-196 absorption in the opinion of the PI, including gastric restrictions and bariatric surgery (eg, gastric bypass).
• Unable to refrain from or anticipates use of medicines defined in the protocol..
• Have been on a diet incompatible with the on-study diet, in the opinion of the PI, within the 28 days before the dose of study drug, and throughout the study.
• Hepatic impaired participants only:
• History or presence of drug abuse within the past 2 years before screening.
• Positive results for the urine or breathalyzer alcohol test and/or urine drug screen at screening or check-in, unless the positive drug screen is due to prescription drug use and is approved by the PI and Acerta Pharma's medical monitor.
• Known history of HIV or hepatitis B virus (HBV) or active infection with hepatitis C virus (HCV). During screening, participants who have active HCV infection or unstable levels of transaminase consistent with active Hepatitis C, will be excluded.
• No hepatic impaired participant will be dosed in both Part 1 and Part 2.
• Healthy control participants only:
• History or presence of clinically significant thyroid disease, in the opinion of the PI.
• History or presence of alcoholism and/or drug abuse within the past 2 years before screening.
• Positive results for the urine or breathalyzer alcohol test and/or urine drug screen at screening.

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (3)

Research Site

Miami, Florida, 33136, United States

Location

Research Site

Orlando, Florida, 32809, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• Priti Patel, MD

  Acerta Pharma BV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: April 30, 2021
• Study Start: October 21, 2014
• Primary Completion: February 2, 2015
• Study Completion: February 2, 2015
• Last Updated: April 30, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (3)