TMC207-TiDP13-C110: Interaction Study With Lopinavir/Ritonavir in Healthy Volunteer

This study has been completed.
Sponsor:
Information provided by:
Tibotec BVBA
ClinicalTrials.gov Identifier:
NCT00828529
First received: January 22, 2009
Last updated: August 14, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Tuberculosis
HIV
Drug: TMC207
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Randomized Crossover Trial to Investigate the Pharmacokinetic Interaction Between Steady-state Lopinavir/Ritonavir and Single-dose TMC207 in Healthy Subjects.

Resource links provided by NLM:


Further study details as provided by Tibotec BVBA:

Primary Outcome Measures:
  • The primary objective is to evaluate the effect of steady-state LPV/rtv 400/100 mg twice daily on the pharmacokinetics of TMC207 and its M2 metabolite after single-dose administration of TMC207 400 mg, in healthy volunteers.

Secondary Outcome Measures:
  • The secondary objectives are: to evaluate the effect of single-dose TMC207 on the steady-state plasma concentrations of lopinavir and ritonavir in healthy volunteers; to evaluate the short-term safety and tolerability of co-administration of single-dose

Enrollment: 16
Study Start Date: February 2009
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Detailed Description:

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00828529

Sponsors and Collaborators
Tibotec BVBA
Investigators
Study Director: Tibotec-Virco Virology BVBA Clinical Trial Tibotec BVBA
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00828529     History of Changes
Obsolete Identifiers: NCT00980291
Other Study ID Numbers: CR002545
Study First Received: January 22, 2009
Last Updated: August 14, 2012
Health Authority: United States: Food and Drug Administration
USA: FOOD AND DRUG ADMINISTRATION - CENTER FOR DRUG EVALUATION AND RESEARCH

Keywords provided by Tibotec BVBA:
TMC207-TiDP13-C110
TMC207-C110
TMC207
Drug-drug interaction
Tuberculosis
HIV
Kaletra
Lopinavir
Ritonavir
Open-label
HIV Infections

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014