TMC125-TiDP2-C197: A Phase I Trial to Investigate the Pharmacokinetic Interaction Between Lopinavir/Ritonavir and TMC125 Both at Steady-state in Healthy Volunteers.

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to determine the effect of steady-state concentrations of LPV, co-administered with a low dose of ritonavir, on the steady-state pharmacokinetics of TMC125 and to determine the effect of steady-state concentrations of TMC125 on the steady-state pharmacokinetics of LPV, co-administered with a low dose of ritonavir.

Detailed Description
-----------------
This is a Phase I, open-label, randomized (patients are assigned different treatments based on chance), 2-period, 2-way cross-over interaction trial to investigate the pharmacokinetic interaction (study of the bodily absorption, distribution, metabolism, and excretion of drugs) between lopinavir/ritonavir (LPV/rtv) and TMC125, both at steady-state.The trial population will consist of 16 healthy volunteers. In 2 consecutive sessions, healthy volunteers will receive Treatment A and Treatment B, in a randomized sequence. In Treatment A, 200 mg TMC125 b.i.d.will be administered for 7 days (from Day 1 to Day 7) with an additional morning dose on Day 8. In Treatment B, 400/100 mgLPV/rtv twice a day will be administered for 15 days (from Day 1 to Day15) with an additional morning dose on Day 16, while 200 mgTMC125 b.i.d. will be co-administered from Day 9 to Day 15 with an additional morning dose on Day 16. Subsequent sessions will be separated by a washout period of at least 2 weeks. Full pharmacokinetic profiles of TMC125 will be determined over the 12-hour dosing interval after the morning intake on Day 8 of Treatment A and on Day 16 of Treatment B. Full pharmacokinetic profiles of LPV and ritonavir will be determined over the 12-hour dosing interval after the morning intake on Days 8 and 16 of Treatment B. All treatments will be administered under fed conditions and will be taken within 10 minutes after a meal. Safety and tolerability evaluations will be recorded continuously. Treatment A = 200 mg TMC125 b.i.d. will be administered for 7 days (from Day 1 to Day 7) with an additional morning dose on Day 8. Treatment B = 400/100 mg LPV/rtv b.i.d. will be administered for 15 days (from Day 1 to Day 15) with an additional morning dose on Day 16, while 200 mg TMC125 b.i.d. will be co-administered from Day 9 to Day 15 with an additional morning dose on Day 16.

Official Title
-----------------
A Phase I, Open-label, Randomized Cross-over, 2-period, 2-way Interaction Trial to Investigate the Pharmacokinetic Interaction Between Lopinavir/Ritonavir and TMC125 Both at Steady-state in Healthy Subjects.

Conditions
-----------------
HIV

Intervention / Treatment
-----------------
* Drug: Etravirine; Lopinavir; Ritonavir


Participation Criteria
=================
Eligibility Criteria
-----------------
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 Normal weight as defined by a Quetelet Index (Body Mass Index [BMI], weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2, extremes included Informed Consent Form (ICF) signed voluntarily before the first trial-related activity Able to comply with protocol requirements Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, electrocardiogram (ECG), vital signs, and the results of blood biochemistry, hematology and a urinalysis carried out at screening. Exclusion Criteria: No positive HIV-1 or HIV-2 test at Screening No hepatitis A infection (confirmed by hepatitis A antibody IgM), or hepatitis B infection (confirmed by hepatitis B surface antigen), or hepatitis C infection (confirmed by hepatitis C virus antibody) at study screening No currently active or underlying gastro-intestinal, cardiovascular, nervous system, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease No currently significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability No history of significant skin disease such as, but not limited to, rash or eruptions, drug allergies, food allergies, dermatitis, eczema, psoriasis, or urticaria No previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication administered in this trial No use of concomitant medication, including over-the-counter products and dietary supplements. Over-the-counter systemic medication must have been discontinued at least 7 days prior to the first dose of study medication prescribed medication and all products containing Hypericum perforatum must have been discontinued at least 14 days before the first dose of study medication, except for paracetamol/acetaminophen and ibuprofen.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Etravirine; Lopinavir; Ritonavir|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the effect of steady-state concentrations of LPV/low dose ritonavir, on the steady-state pharmacokinetics of TMC125 and vice versa. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the short-term safety and tolerability of the concomitant use of TMC125 and LPV, co-administered with low-dose ritonavir in healthy volunteers. |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TMC125-C197, TMC125-TiDP2-C197, HIV, DDI, Lopinavir, Intelence, Kaletra, Ritonavir, Etravirine, Interaction, Pharmacokinetics, Steady-state