A Study to Investigate the Effect of Steady-State TMC278 on the Pharmacokinetics of a Single Dose of Digoxin

Condition(s) targeted: Healthy

Intervention: Treatment A: Digoxin (Drug); Treatment B: TMC278 (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Janssen R&D Ireland

Official(s) and/or principal investigator(s):
Janssen R&D Ireland Clinical Trial, Study Director, Affiliation: Janssen R&D Ireland

The purpose of this study is to investigate the effect of steady-state (constant concentration of medication in the blood) TMC278 on the single dose pharmacokinetics (what the body does to the medication) of digoxin.

Official title: A Phase I, Open Label, Randomized, Crossover Trial in Healthy Subjects to Investigate the Effect of Steady-state TMC278 on the Pharmacokinetics of a Single Dose of Digoxin

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Maximum plasma concentration (Cmax) of digoxin following single dose administration of digoxin co-administered with TMC278, compared to single dose administration of digoxin

Area under the plasma concentration versus time curve (AUC) of digoxin following single dose administration of digoxin co-administered with TMC278, compared to single dose administration of digoxin

Secondary outcome: Number of participants with adverse events

Detailed description: This is an open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), crossover (method used to switch patients from one treatment arm to another in a clinical study) study to investigate the effect of steady-state TMC278 on the single dose pharmacokinetics of digoxin. The study consists of 3 phases, including screening phase, treatment phase, and follow-up phase. After the screening phase, participants will be randomized to one of 2 treatment sequences consisting of Treatments A and B, ie, Sequence AB (11 participants), and Sequence BA (11 participants). Treatment phase includes, Treatment A: digoxin 0. 5 mg (single oral dose), and Treatment B: TMC278 25 mg once daily with digoxin 0. 5 mg (single oral dose). The 2 consecutive sequences will be separated by a washout period (period when receiving no treatment) of at least 14 days. Safety evaluations for adverse events, clinical laboratory tests, electrocardiograms, cardiac telemetry, vital signs, physical examination, alcohol breath test, and specific toxicities will be monitored throughout the study. The study duration for treatment phase will be at least 26 days.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Women must be postmenopausal for at least 2 years, or be surgically sterile

- Men must agree to use a highly effective method of birth control and to not donate

sperm during the study and for 3 months after receiving the last dose of study medication Exclusion Criteria:

- A positive HIV-1 or HIV-2 test at screening

- Hepatitis A, B or C infection at screening

- History of clinically relevant heart rhythm disturbances

- History of idiopathic hypertrophic subaortic stenosis, atrioventricular block,

ventricular tachycardia/ventricular fibrillation or family history of sudden cardiac death

Merksem, Belgium

A Phase I, open label, randomized, crossover trial in healthy subjects to investigate the effect of steady-state TMC278 on the pharmacokinetics of a single dose of digoxin.

Starting date: January 2012
Last updated: March 1, 2013