tmc125-tidp2-c197: a phase i trial to investigate the pharmacokinetic interaction between lopinavir/ritonavir and tmc125 both at steady-state in healthy volunteers.

Conditions: HIV

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.

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.

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.

Keywords: tmc125-c197 tmc125-tidp2-c197 hiv ddi lopinavir intelence kaletra ritonavir etravirine interaction pharmacokinetics steady-state