Clinical trial NCT02271438: A Study to Evaluate the Effects of Ibrutinib on Cardiac Repolarization in Healthy Participants
Official title: A Randomized, Double-Blind, Placebo- and Positive-Controlled, Single-Dose, Four-Way Crossover Study to Evaluate the Effects of Ibrutinib on Cardiac Repolarization in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Ibrutinib
Moxifloxacin
Cardiac Repolarization
Electrocardiogram
QTc interval
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-10-22
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from baseline in QTc interval
timeFrame: Baseline (predose) up to Day 4
measure: Number of Participants with Adverse events
timeFrame: Up to Day 12 of the follow-up period
Secondary outcomes:
measure: Change from baseline in RR interval
timeFrame: Baseline (predose) up to Day 4
measure: Change from baseline in heart rate
timeFrame: Baseline (predose) up to Day 4
measure: Change from baseline in PR interval
timeFrame: Baseline (predose) up to Day 4
measure: Change from baseline in QRS interval
timeFrame: Baseline (predose) up to Day 4
measure: Plasma concentration of ibrutinib following administration of a single dose
timeFrame: Predose (before tablet intake), up to 72 hours after dose
measure: Plasma concentration of the Metabolite, PCI-45227, following administration of a single dose of ibrutinib
timeFrame: Predose (before tablet intake), up to 72 hours after dose
measure: Plasma concentration of moxifloxacin following administration of a single dose
timeFrame: Predose (before tablet intake), up to 72 hours after dose
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.