TMC125-TiDP2-C187: A Phase I, Open-label Trial to Investigate the Pharmacokinetic Interaction Between TMC125 and Two Antifungal Agents (Fluconazole and Voriconazole), All at Steady-state in Healthy Subjects.

• Status: Completed
• Trial end date: 2009-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase I, open-label, 3-period crossover trial to investigate the pharmacokinetic interaction (process by which a drug is absorbed, distributed, metabolised and eliminated by the body) between TMC125 and fluconazole, and between TMC125 and voriconazole.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tibotec Pharmaceuticals, Ireland
• Treatments: Antifungal Agents; Etravirine; Fluconazole; Miconazole; Voriconazole

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 screening

• Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, extremes included. BMI is calculated as the weight (in kg) divided by the square of height (in m)

• Informed Consent Forms signed voluntarily before first trial-related activity

• Able to comply with protocol requirements

• Healthy on the basis of medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination (including skin examination), medical and surgical history, electrocardiogram (ECG), vital signs and the results of blood biochemistry, hematology and a urinalysis carried out at Screening.

Exclusion Criteria:

• A positive HIV-1 or HIV-2 test at study screening

• Female, except if postmenopausal since more than two years, or post-hysterectomy or surgically sterilized (without reversal operation)

• History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use which in the investigator's opinion would compromise subject's safety and/or compliance with study procedures

• Hepatitis A infection, hepatitis B infection, or hepatitis C infection at study screening

• A positive urine drug test at study screening or on Day -1 of each session. Urine will be tested for the presence of amphetamines, benzodiazepines, cocaine, cannabinoids and opioids

• Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease

• Currently significant diarrhea, gastric stasis or constipation that in the investigator's opinion could influence drug absorption or bioavailability

• Any history of significant skin disease. Previously demonstrated clinically significant allergy or hypersensitivity to fluconazole, voriconazole and/or any of the excipients of the investigational medication administered in this trial

• Clinical evidence or history of long QT syndrome and history of additional risk factors for Torsade de Pointes, such as cardiomyopathy, heart failure, hypokalemia, family history of known Long QT Syndrome, or sudden unexplained death at a young age (= 40 years) in a firstdegree relative (i.e., biological parent, sibling, or offspring)

• Clinically relevant heart rhythm disturbances known or suggested by history, or on 12-lead ECG at screening or on Day 1 (predose) of the first treatment period

• Electrolyte abnormalities (hypokalemia, hypocalcemia, hypomagnesemia), grade 2 or greater, within 21 days prior to intake of the investigational medication

• History of galactose intolerance, lactase deficiency or glucose-galactose malabsorption

• Use of concomitant medication, including over-the-counter products and dietary supplements

• Systemic over-the-counter 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 (e.g. St. John's wort) must have been discontinued at least 14 days before the first dose of study medication, except for paracetamol

• Participation in an investigational drug trial within 60 days prior to the first intake of trial medication

• Donation of blood or plasma within the 60 days preceding the first drug intake

• Having participated in more than 1 trial with TMC125 (etravirine), TMC120 (dapirivine) and/or TMC278 (rilpivirine, formerly known as R278474) or having developed rash, erythema or urticaria while participating in a trial with the aforementioned compounds

• Subjects with the laboratory abnormalities at screening as defined by the Division of AIDS and in accordance with the normal ranges of clinical laboratory.