Merksem, Belgium
NCT Number: NCT02271438
A Study to Evaluate the Effects of Ibrutinib on Cardiac Repolarization in Healthy Participants
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.
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Notify MeKey information
Conditions
Age range
18 year–55 year
Sex eligibility
All sexes
Study type
Interventional
Phase
Phase 1
Primary location
About this study
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.
Who can participate
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
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
Treatment and study plan
Ibrutinib
DrugParticipants 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
DrugParticipants will receive a single oral dose of 1 moxifloxacin capsule (400 mg) in Treatment D.
Ibrutinib-matching placebo
DrugParticipants 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
DrugParticipants will receive a single oral dose of 1 moxifloxacin-matching placebo capsule in Treatment A, B, and C.
Primary outcomes
-
Change from baseline in QTc interval
Time frame: Baseline (predose) up to Day 4
The QTc interval, as measured by electrocardiograms will evaluate the potential effect of ibrutinib on QTc interval duration.
-
Number of Participants with Adverse events
Time frame: Up to Day 12 of the follow-up period
Secondary outcomes
-
Change from baseline in RR interval
Time frame: Baseline (predose) up to Day 4
The RR interval is the portion between two consecutive R waves in the electrocardiogram.
-
Change from baseline in heart rate
Time frame: Baseline (predose) up to Day 4
-
Change from baseline in PR interval
Time frame: Baseline (predose) up to Day 4
The PR interval is the portion of the electrocardiogram between the onset of the P wave (atrial depolarization) and the QRS complex (ventricular depolarization).
-
Change from baseline in QRS interval
Time frame: Baseline (predose) up to Day 4
The QRS interval is the interval from the beginning of the Q wave to the termination of the S wave, representing the time for ventricular depolarization.
-
Plasma concentration of ibrutinib following administration of a single dose
Time frame: Predose (before tablet intake), up to 72 hours after dose
Plasma concentrations of ibrutinib are used to evaluate when the highest concentration is achieved in the body and how long it stays in the body.
-
Plasma concentration of the Metabolite, PCI-45227, following administration of a single dose of ibrutinib
Time frame: Predose (before tablet intake), up to 72 hours after dose
Plasma concentrations of the metabolite, PCI-45227, are used to evaluate when the highest concentration is achieved in the body and how long it stays in the body.
-
Plasma concentration of moxifloxacin following administration of a single dose
Time frame: Predose (before tablet intake), up to 72 hours after dose
Plasma concentrations of moxifloxacin are used to evaluate when the highest concentration is achieved in the body and how long it stays in the body.
Sponsors and collaborators
Lead sponsor
Janssen Research & Development, LLC
Industry
Registry information
Official study 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
Important dates
- Study start
- 2014
- Primary completion
- 2015
- Study completion
- 2015
- First posted
- Oct 22, 2014
- Registry last updated
- Jun 6, 2016
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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