TMC207-TiDP13-C110: Interaction Study With Lopinavir/Ritonavir in Healthy Volunteer

Sponsor

Tibotec BVBA (Industry)

Overall Status

Completed

CT.gov ID

NCT00828529

Collaborator

(none)

Enrollment

2.9

Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this Phase I, open-label, randomized crossover trial is to investigate the pharmacokinetic interaction between steady-state lopinavir/ritonavir and single-dose TMC207 in healthy volunteers.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis HIV	Drug: TMC207	Phase 1

Detailed Description

TMC207 is being investigated for the treatment of MDR-TB infection. This is a Phase I, open-label, randomized crossover trial in healthy volunteers to investigate the potential interaction between steady-state lopinavir/ritonavir (LPV/rtv) 400/100 mg twice daily and a single dose of 400 mg TMC207. The trial population will consist of 16 healthy volunteers. During 2 sessions, each participant will receive 2 treatments (Treatments A and B) in a randomized order. This means it will be decided by chance if subjects will receive first treatment A, then B or first treatment B, then A.

In Treatment A, participants will receive a single dose of TMC207 400 mg on Day 1. In Treatment B, participants will receive LPV/rtv 400/100 mg twice daily on Days 1 to 24, while on Day 11 a single dose of TMC207 400 mg will be co-administered. The two single doses of TMC207 will be administered 4 weeks apart. Consequently, Treatment B should start 4 days after completion of Treatment A, and Treatment A should start 14 days after completion of Treatment B (counting from the day the last PK sample has been collected). Pharmacokinetic profiles over 336 hours will be determined for TMC207 and its N-monodesmethyl metabolite (M2) after administration of TMC207 400 mg alone (Day 1 of Treatment A), and in combination with steady-state LPV/rtv (Day 11 of Treatment B). Morning predose concentrations of lopinavir and ritonavir will be determined at several time points. Safety and tolerability will be evaluated throughout the trial. Day 1 of Treatment A and on Day 11 of Treatment B, 400 mg TMC207 (1 tablet) will be taken orally in the morning within 10 mins. after completion of a meal. Days 1 to 24 of Treatment B, 2 tablets of Lopinavir/Ritonavir (LPV/rtv = 400 mg lopinavir and 100 mg ritonavir) will be taken in the morning and evening. When LPV/rtv is administered alone, it can be taken with or without food. When co-administered simultaneously with TMC207, LPV/rtv intake will be within 10 mins. after completion of a meal.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Open-label, Randomized Crossover Trial to Investigate the Pharmacokinetic Interaction Between Steady-state Lopinavir/Ritonavir and Single-dose TMC207 in Healthy Subjects.

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

May 1, 2009

Outcome Measures

Primary Outcome Measures

The primary objective is to evaluate the effect of steady-state LPV/rtv 400/100 mg twice daily on the pharmacokinetics of TMC207 and its M2 metabolite after single-dose administration of TMC207 400 mg, in healthy volunteers. []

Secondary Outcome Measures

The secondary objectives are: to evaluate the effect of single-dose TMC207 on the steady-state plasma concentrations of lopinavir and ritonavir in healthy volunteers; to evaluate the short-term safety and tolerability of co-administration of single-dose []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to selection
Body Mass Index of 18.0 to 32.0 kg/m2, extremes included
Able to comply with protocol requirements
Healthy on the basis of a physical examination, medical history, ECG, vital signs and the results of blood biochemistry and hematology test and a urinalysis carried out at screening
Informed Consent Form signed voluntarily before the first trial-related activity.

Exclusion Criteria:

A positive HIV-1 or HIV-2 test
Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post-surgical sterilization
Hepatitis A, B, or C infection
Evidence of current use of illicit drugs or opioids or abuse of alcohol
Currently active or underlying disorders including gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease
Any history of significant skin disease or allergy including allergy or hypersensitivity to any of the excipients of the investigational medication administered in this trial
Use of concomitant medication, including over-the-counter products and dietary supplements, except for ibuprofen and paracetamol up to 3 days before the first dose of trial medication
Recent donation of blood or plasma or participation in a clinical trial
Subjects with QTc prolongation or any other clinically significant ECG abnormality or a family history of Long QT Syndrome.