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

NCT ID: NCT02271438

Last Updated: 2016-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2015-05-31

Brief Summary

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.

Detailed 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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1: Ibrutinib 840 milligram (mg)

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

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Participants will receive a single oral dose of 12 capsules (12\*140 mg capsules) of ibrutinib in Treatment A and 6 capsules (4 6\*140 mg capsules) of ibrutinib in Treatment B.

Part 1: Ibrutinib 1680 mg

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

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Participants will receive a single oral dose of 12 capsules (12\*140 mg capsules) of ibrutinib in Treatment A and 6 capsules (4 6\*140 mg capsules) of ibrutinib in Treatment B.

Part 2: Treatment A

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

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Participants will receive a single oral dose of 12 capsules (12\*140 mg capsules) of ibrutinib in Treatment A and 6 capsules (4 6\*140 mg capsules) of ibrutinib in Treatment B.

Moxifloxacin-matching placebo

Intervention Type: DRUG

Participants will receive a single oral dose of 1 moxifloxacin-matching placebo capsule in Treatment A, B, and C.

Part 2: Treatment B

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

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Participants will receive a single oral dose of 12 capsules (12\*140 mg capsules) of ibrutinib in Treatment A and 6 capsules (4 6\*140 mg capsules) of ibrutinib in Treatment B.

Moxifloxacin-matching placebo

Intervention Type: DRUG

Participants will receive a single oral dose of 1 moxifloxacin-matching placebo capsule in Treatment A, B, and C.

Part 2: Treatment C

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

Group Type: EXPERIMENTAL

Ibrutinib-matching placebo

Intervention Type: DRUG

Participants will receive a single oral dose of 12 ibrutinib-matching placebo capsules in Treatment B and 6 ibrutinib-matching placebo capsules in Treatment C and D.

Moxifloxacin-matching placebo

Intervention Type: DRUG

Participants will receive a single oral dose of 1 moxifloxacin-matching placebo capsule in Treatment A, B, and C.

Part 2: Treatment D

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

Group Type: EXPERIMENTAL

Moxifloxacin

Intervention Type: DRUG

Participants will receive a single oral dose of 1 moxifloxacin capsule (400 mg) in Treatment D.

Ibrutinib-matching placebo

Intervention Type: DRUG

Participants will receive a single oral dose of 12 ibrutinib-matching placebo capsules in Treatment B and 6 ibrutinib-matching placebo capsules in Treatment C and D.

Interventions

Ibrutinib

Participants will receive a single oral dose of 12 capsules (12\*140 mg capsules) of ibrutinib in Treatment A and 6 capsules (4 6\*140 mg capsules) of ibrutinib in Treatment B.

Intervention Type: DRUG

Moxifloxacin

Participants will receive a single oral dose of 1 moxifloxacin capsule (400 mg) in Treatment D.

Intervention Type: DRUG

Ibrutinib-matching placebo

Participants will receive a single oral dose of 12 ibrutinib-matching placebo capsules in Treatment B and 6 ibrutinib-matching placebo capsules in Treatment C and D.

Intervention Type: DRUG

Moxifloxacin-matching placebo

Participants will receive a single oral dose of 1 moxifloxacin-matching placebo capsule in Treatment A, B, and C.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Merksem, , Belgium

Countries

Belgium

References

de Jong J, Hellemans P, Jiao JJ, Huang Y, Mesens S, Sukbuntherng J, Ouellet D. Ibrutinib does not prolong the corrected QT interval in healthy subjects: results from a thorough QT study. Cancer Chemother Pharmacol. 2017 Dec;80(6):1227-1237. doi: 10.1007/s00280-017-3471-x. Epub 2017 Oct 28.

Reference Type: DERIVED

PMID: 29080970 (View on PubMed)

Other Identifiers

PCI-32765CLL1007

Identifier Type: OTHER

Identifier Source: secondary_id

2014-000081-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR103807

Identifier Type: -

Identifier Source: org_study_id