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

Tibotec Pharmaceutical

Status and phase

Completed

Phase 1

Conditions

HIV

Treatments

Drug: Etravirine; Lopinavir; Ritonavir

Study type

Interventional

Funder types

Industry

Identifiers

NCT00767117

CR015526

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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.