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

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.

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Etravirine; Lopinavir; 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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tibotec Pharmaceuticals, Ireland

Publications and helpful links

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: October 3, 2008
• First Submitted That Met QC Criteria: October 3, 2008
• First Posted (Estimate): October 6, 2008

Study Record Updates

• Last Update Posted (Estimate): June 9, 2011
• Last Update Submitted That Met QC Criteria: June 8, 2011
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: HIV; Pharmacokinetics; Ritonavir; Kaletra; Etravirine; Intelence; Interaction; Lopinavir; Steady-state; TMC125-C197; TMC125-TiDP2-C197; DDI
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir; Etravirine
• Other Study ID Numbers: CR015526