A Study to Evaluate the Effect of ACP-196 on the Heart Rate-corrected QT Interval in Healthy Adult Participants

NCT04867980 | Completed Phase 1 FDA Drug

• 1 other identifier: ACE-HV-005
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the effects of single therapeutic and supratherapeutic oral doses of ACP-196 on the heart rate-corrected QT interval using Fridericia's formula (QTcF).

Conditions

Healthy Volunteers

Keywords

ACE-HV-005; ACP-196; Healthy participants; Volunteers; Adults; QTc Interval; Pharmacokinetics; PK

Outcome Measures

Primary Outcomes (1)

• The QTcF Change From Baseline at Postdose Timepoints (dQTcF)

  0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period

Secondary Outcomes (20)

• Change in Time-matched QTcF Interval Following Moxifloxicin Administration Compared With Matching Placebo

  1, 2, 3, and 4 hour post moxifloxicin dose in each period

• Change From Baseline in Heart Rate at Postdose Time Points

  0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period

• Change From Baseline in PR Interval at Postdose Time Points

  0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period

• Change From Baseline in RR Interval at Postdose Time Points

  0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period

• Change From Baseline in QRS Interval at Postdose Time Points

  0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in each period

Study Arms (4)

ABCD

EXPERIMENTAL

Participant will receive a single oral dose of 4 study treatments with the sequences of ABCD. The washout period will be \>= 5 days between each dose.

Drug: ACP-196; Drug: Moxifloxacin 400 mg; Drug: Placebo

BDAC

EXPERIMENTAL

Participant will receive a single oral dose of 4 study treatments with the sequences of BDAC. The washout period will be \>= 5 days between each dose.

Drug: ACP-196; Drug: Moxifloxacin 400 mg; Drug: Placebo

CADB

EXPERIMENTAL

Participant will receive a single oral dose of 4 study treatments with the sequences of CADB. The washout period will be \>= 5 days between each dose.

Drug: ACP-196; Drug: Moxifloxacin 400 mg; Drug: Placebo

DCBA

EXPERIMENTAL

Participant will receive a single oral dose of 4 study treatments with the sequences of DCBA. The washout period will be \>= 5 days between each dose.

Drug: ACP-196; Drug: Moxifloxacin 400 mg; Drug: Placebo

Interventions

ACP-196 DRUG

Participants will receive a single oral dose of 100 mg ACP-196 (1 x 100 mg capsule) on Day 1 (Treatment A) and 400 mg ACP-196 (4 x 100 mg capsules) on Day 1 (Treatment B) according to the randomization scheme.

Also known as: Acalabrutinib

ABCD; BDAC; CADB; DCBA

Moxifloxacin 400 mg DRUG

Participants will receive a single oral dose of 400 mg moxifloxacin (1 x 400 mg tablet) on Day 1 (Treatment C) according to the randomization scheme.

ABCD; BDAC; CADB; DCBA

Placebo DRUG

Participants will receive a single oral dose of ACP-196 matching placebo (4 x 100 mg matching placebo capsules) and moxifloxacin matching placebo (1 x 400 mg matching placebo tablet) on Day 1 (Treatment D) according to the randomization scheme.

ABCD; BDAC; CADB; DCBA

Eligibility Criteria

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

You may qualify if:

• Continuous non-smoker participant who has not used nicotine-containing products for \>= 3 months before the first dose
• Have body mass index of \>= 18.0 and \<= 32.0 kg/m\^2 at screening
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the principal investigator (PI)
• No clinically significant history or presence of ECG findings as judged by the PI or qualified designee at screening and each check-in, including each criterion as: 1) Normal sinus rhythm (heart rate between 50 and 100 beats per minute \[bpm\]), 2) QTcF interval ≤ 450 milliseconds (msec), 3) QRS interval ≤ 110 msec, and 4) PR interval ≤ 220 msec
• Women participants must be of non-childbearing status
• Women participants must have negative serum pregnancy test
• ability to swallow multiple capsules and/or tablets using size 0 blank capsules (up to a maximum of 5 capsules per participant)
• Male participants must be willing to use protocol specified contraception methods

You may not qualify if:

• 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
• History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study
• Presence of any clinically significant, ongoing systemic bacterial, fungal, or viral infections (including upper respiratory tract infections, but excluding localized cutaneous fungal infections), in the opinion of the PI
• History of any major surgical procedure within 30 days before the first dose of study drug
• History or presence of alcoholism or drug abuse within the past 2 years before screening
• 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).
• Allergy to band-aids, adhesive dressing, or medical tape
• History or presence of clinically significant thyroid disease
• Prior exposure to Bruton's tyrosine kinase inhibitors (eg, ACP-196, ibrutinib) within 3 months before the first dose of study drug
• Positive urine cotinine at screening
• Positive urine drug or alcohol results at screening or each check-in
• Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at screening
• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening
• Seated heart rate is lower than 50 bpm or higher than 99 bpm at screening
• Unable to refrain from or anticipates the use of protocol defined medications for 28 days before the first dose of study drug and throughout the study

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

acalabrutinib; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Priti Patel, MD

  Acerta Clinical Trials

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: April 30, 2021
• Study Start: April 1, 2016
• Primary Completion: May 9, 2016
• Study Completion: May 9, 2016
• 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 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)