A Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, Food Effects, and Drug-drug Interactions of ACP-196 in Healthy Participants

NCT04901923 | Completed Phase 1 FDA Drug

• 1 other identifier: ACE-HV-001
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the safety, pharmacokinetics/pharmacodynamics (PK/PD), food-effect, and drug-drug interaction study of ACP-196 in healthy participants.

Conditions

Healthy Participants

Keywords

Acalabrutinib; ACP-196; Drug-drug interaction; Food effects; Healthy participants; Itraconazole; Pharmacodynamics; Pharmacokinetics; PK

Outcome Measures

Primary Outcomes (11)

• Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of ACP-196 in Parts 1, 2, and 3

  Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

• Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196 in Parts 1, 2, and 3

  Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

• Maximum Observed Plasma Concentration (Cmax) of ACP-196 in Parts 1, 2, and 3

  Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

• Time to reach Cmax (Tmax) of ACP-196 in Parts 1, 2, and 3

  Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

• Terminal-elimination Half-life (T1/2) of ACP-196 in Parts 1, 2, and 3

  Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

• Terminal-elimination Rate Constant (λz) of ACP-196 in Parts 1, 2, and 3

  Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

• Time Delay Between the Time of Dosing and the First Measurable Concentration (tlag) of ACP-196 in Parts 1, 2, and 3

  Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

• Incidences of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  Part 1: Day 1 through Day 3; Part 2 and Part 3: Day 1 through Day 10

• Incidences of Abnormal Vital Signs Reported as TEAEs

  Part 1: Day 1 ( from 1 hr predose through 1 hr postdose); Part 2: From Day 1 (1 hr predose) through Day 8 (1 hr postdose); Part 3: From Day 1 (1 hr predose) through Day 9 (1 hr postdose)

• Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs

  Part 1: From Day 1 to Day 2; Part 2 and Part 3: From Day 1 to Day 10

• Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs

  Part 1: Day 1 ( from 1 hr predose through 1 hr postdose); Part 2: From Day 1 (1 hr predose) through Day 8 (1 hr postdose); Part 3: From Day 1 (1 hr predose) through Day 9 (1 hr postdose)

Secondary Outcomes (2)

• Occupancy of Bruton's Tyrosine Kinase (BTK) by ACP-196 in Peripheral Blood Mononuclear Cells (PBMCs)

  1, 3, 12, 15, and 24 hrs after first dose on Day 1

• Effect of ACP-196 on Biologic Markers of B-cell Function

  1, 3, 12, 15, and 24 hrs after first dose on Day 1

Study Arms (7)

Part 1 Cohort 1

EXPERIMENTAL

Participants will receive ACP-196 2.5 mg capsule orally BID on Day 1.

Drug: ACP-196

Part 1 Cohort 2

EXPERIMENTAL

Participants will receive ACP-196 5 mg (2 x 2.5 mg capsules) orally BID on Day 1.

Drug: ACP-196

Part 1 Cohort 3

EXPERIMENTAL

Participants will receive ACP-196 25 mg capsule orally BID on Day 1.

Drug: ACP-196

Part 1 Cohort 4

EXPERIMENTAL

Participants will receive ACP-196 50 mg (2 x 25 mg capsules) orally BID on Day 1.

Drug: ACP-196

Part 1 Cohort 5

EXPERIMENTAL

Participants will receive ACP-196 100 mg (4 x 25 mg capsules) orally QD on Day 1.

Drug: ACP-196

Part 2 Cohort 6

EXPERIMENTAL

Participants will receive ACP-196 75 mg (3 x 25 mg capsules) orally QD on Day 1 and Day 8.

Drug: ACP-196

Part 3 Cohort 7

EXPERIMENTAL

Participants will receive ACP-196 50 mg (2 x 25 mg capsules) orally QD on Day 1, itraconazole 200 mg capsules BID from Days 4 to 8 with meals and then ACP-196 50 mg (2 x 25 mg capsules) along with itraconazole 200 mg capsule QD on Day 9 under fasting state.

Drug: ACP-196; Drug: Itraconazole

Interventions

ACP-196 DRUG

Participants will receive ACP-196 oral capsule(s) in all parts.

Also known as: Acalabrutinib

Part 1 Cohort 1; Part 1 Cohort 2; Part 1 Cohort 3; Part 1 Cohort 4; Part 1 Cohort 5; Part 2 Cohort 6; Part 3 Cohort 7

Itraconazole DRUG

Participants will receive itraconazole 200 mg capsules BID from Days 4 to 8 with meals and then 200 mg capsule QD on Day 9 under fasting state.

Part 3 Cohort 7

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) \>=18.0 and \<=30.0 kg/m\^2.
• Healthy as determined by medical history and physical examination.
• Nonsmoker
• Normal clinical laboratory test results and ECG, or results with minor deviations which are not considered to be clinically significant in the judgment of the investigator.
• Men of and women of childbearing potential to follow protocol defined contraception methods.
• Women must have negative urine pregnancy test.
• Willingness and ability to swallow study drug capsules.

You may not qualify if:

• Prior or ongoing clinically significant illness, medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections).
• Women cannot be pregnant or breast feeding.
• Significant history of drug or alcohol abuse or addiction within 3 years before study screening or as evidenced by continuing medical complications of prior drug or alcohol use.
• History of blood or plasma donation within 90 days before first study drug administration.
• Currently drinking over 21 units/week of ethanol
• Drug toxicology screen positive for any prohibited drugs, illicit substances, or alcohol.
• Anticipated need for alcohol, tobacco, or any drug during the study drug administration and immediate follow-up periods.
• Relative to admission has any of the following exposures: has taken a prescription systemic medication within 14 days; has used an over-the counter systemic medication (other than acetaminophen) within 7 days; has ingested calcium supplements or calcium-containing vitamins within 7 days; has ingested grapefruit, grapefruit juice, or grapefruit-containing products within 7 days; has consumed alcohol within 48 hours; has taken acetaminophen within 24 hours.
• Positive test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen or hepatitis B core antibody, or hepatitis C antibody.
• Unwillingness to avoid vigorous physical activity during inpatient clinic confinements.
• Part 2 only - Inability or unwillingness to eat all of the ingredients of the high-fat, high-calorie meal as specified in the protocol.
• Part 3 only - Known allergy to itraconazole or other azole compounds.

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

acalabrutinib; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Design

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

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 26, 2021
• Study Start: March 15, 2014
• Primary Completion: May 22, 2014
• Study Completion: May 22, 2014
• Last Updated: May 26, 2021

Record last verified: 2021-05

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 de-identified 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 (1)