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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Bedaquiline
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
Antitubercular Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on September 15, 2014