A Study to Evaluate the Effects of Ibrutinib on Cardiac Repolarization in Healthy Participants

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Ibrutinib-matching placebo; Drug: Moxifloxacin; Drug: Ibrutinib; Drug: Moxifloxacin-matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02271438

2014-000081-22 (EudraCT Number)

CR103807

PCI-32765CLL1007 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to assess the safety and tolerability of ibrutinib, to compare the pharmacokinetics of ibrutinib after single oral administration of 840 mg and 1680 mg and to assess the effects of a single dose of ibrutinib on QT/QTc intervals and electrocardiogram (ECG) in healthy adults.

Full description

The study consists of 2 parts: Part 1 and Part 2. Part 1 is an open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving), single-center, 2-period, sequential design part. It consists of a Screening phase (Day-21 to -2), Treatment Period 1 and Treatment Period 2. In treatment period 1, 8 participants including two women will receive 840 milligram (mg) ibrutinib capsules + 6 placebo capsules. In treatment period 2, participants will receive 1680 mg ibrutinib capsules. Treatment periods will be separated by a Washout period of not less than 7 days. A high-fat breakfast will be provided 2 hours before dosing. Blood samples will be collected after each dosing for pharmacokinetic assessments.

Part 2 is a randomized (the study medication is assigned by chance), placebo (an inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study) and positive-controlled (participants are assigned to either a recognized effective treatment or the study medication), double-blind (neither physician nor participant knows the treatment that the participant receives), single dose, and 4-way crossover (the same medications are provided to all participants but in a different sequence) part. Participants will receive either of the 4 treatments: Treatment A (Ibrutinib 1680 mg + moxifloxacin-matching placebo); Treatment B (Ibrutinib 840 mg+ ibrutinib-matching placebo + moxifloxacin-matching placebo); Treatment C (ibrutinib-matching placebo + moxifloxacin-matching placebo); and Treatment D: (moxifloxacin 400 mg + ibrutinib-matching placebo). Each treatment period will be separated by a Washout period of not less than 7 days. Electrocardiogram (ECG) will be recorded. Participants' safety will be monitored throughout the study.

Enrollment: 28 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Must sign an informed consent document indicating they understand the purpose of the study and procedures
• Must have a body mass index (BMI) of between 18 and 30 kg/m^2, inclusive
• Must have a body weight of not less than 50 kg
• Must have a blood pressure between 90 and 140 mmHg inclusive, systolic, and no higher than 90 mmHg diastolic at screening
• Must have an average of triplicate 12-lead ECG recordings, completed within 5 minutes total, consistent with normal cardiac conduction and function

Exclusion criteria

• History of or current clinically significant medical illness
• Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram
• History of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardias, and heart blocks
• Use of any prescription or nonprescription medication (including vitamins and herbal supplements
• Donated blood or blood products or had substantial loss of blood within 3 months before screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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28 participants in 6 patient groups

Part 1: Ibrutinib 840 milligram (mg)

Experimental group

Description:

Participants will receive ibrutinib 840 mg (6\*140 mg capsules) + 6 placebo capsules on Day 1 of Part 1, Period 1.

Treatment:

Drug: Ibrutinib

Part 1: Ibrutinib 1680 mg

Experimental group

Description:

Participants will receive ibrutinib 1680 mg (12\*140 mg capsules) on Day 1 of Part 1, Period 2.

Treatment:

Drug: Ibrutinib

Part 2: Treatment A

Experimental group

Description:

Participants will receive ibrutinib, 1680 mg (12\*140 mg capsules) + 1 moxifloxacin-matching placebo capsule Day 1of Part 2.

Treatment:

Drug: Ibrutinib

Drug: Moxifloxacin-matching placebo

Part 2: Treatment B

Experimental group

Description:

Participants will receive ibrutinib, 840 mg (6\*140 mg capsules) + 6 ibrutinib-matching placebo capsules + 1 moxifloxacin-matching placebo capsule.

Treatment:

Drug: Ibrutinib

Drug: Moxifloxacin-matching placebo

Part 2: Treatment C

Experimental group

Description:

Participants will receive placebo (12 ibrutinib-matching placebo capsules + 1 moxifloxacin-matching placebo capsule) Day 1 of Part 2.

Treatment:

Drug: Ibrutinib-matching placebo

Drug: Moxifloxacin-matching placebo

Part 2: Treatment D

Experimental group

Description:

Participants will receive moxifloxacin 400 mg (1 capsule) + 12 ibrutinib-matching placebo capsules Day 1 of Part 2.

Treatment:

Drug: Ibrutinib-matching placebo

Drug: Moxifloxacin