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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02271438
• Other study ID #: CR103807
• Secondary ID: PCI-32765CLL1007
• Status: Completed
• Phase: Phase 1
• First received: October 20, 2014
• Last updated: June 3, 2016
• Start date: October 2014
• Est. completion date: May 2015

Study information

• Verified date: June 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: May 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• 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.
• Moxifloxacin
Participants will receive a single oral dose of 1 moxifloxacin capsule (400 mg) in Treatment D.
• 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.
• Moxifloxacin-matching placebo
Participants will receive a single oral dose of 1 moxifloxacin-matching placebo capsule in Treatment A, B, and C.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in QTc interval	The QTc interval, as measured by electrocardiograms will evaluate the potential effect of ibrutinib on QTc interval duration.	Baseline (predose) up to Day 4	No
Primary	Number of Participants with Adverse events		Up to Day 12 of the follow-up period	Yes
Secondary	Change from baseline in RR interval	The RR interval is the portion between two consecutive R waves in the electrocardiogram.	Baseline (predose) up to Day 4	No
Secondary	Change from baseline in heart rate		Baseline (predose) up to Day 4	No
Secondary	Change from baseline in PR interval	The PR interval is the portion of the electrocardiogram between the onset of the P wave (atrial depolarization) and the QRS complex (ventricular depolarization).	Baseline (predose) up to Day 4	No
Secondary	Change from baseline in QRS interval	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.	Baseline (predose) up to Day 4	No
Secondary	Plasma concentration of ibrutinib following administration of a single 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.	Predose (before tablet intake), up to 72 hours after dose	No
Secondary	Plasma concentration of the Metabolite, PCI-45227, following administration of a single dose of ibrutinib	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.	Predose (before tablet intake), up to 72 hours after dose	No
Secondary	Plasma concentration of moxifloxacin following administration of a single 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.	Predose (before tablet intake), up to 72 hours after dose	No