tmc207-tidp13-c110: interaction study with lopinavir/ritonavir in healthy volunteer

Conditions: Tuberculosis; HIV

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.

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.

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 * 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.

Keywords: tmc207-tidp13-c110 tmc207-c110 tmc207 drug-drug interaction tuberculosis hiv kaletra lopinavir ritonavir open-label hiv infections