TMC435-TiDP16-C114 - A Study in Healthy Volunteers Investigating the Pharmacokinetic Interaction Between TMC435 and the Antiretroviral Agents TMC278 and Tenofovir

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT01205139
First received: September 16, 2010
Last updated: November 23, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to investigate the effect of steady-state concentrations of TMC435 on the steady-state pharmacokinetics of TMC278 or Tenofovir , and vice versa. Steady state is a term which means that the drug has been given long enough so that the plasma concentrations will remain the same with each subsequent dose. TMC435 is being investigated for the treatment of chronic hepatitis C virus (HCV) infection. TMC278 and Tenofovir are two antiretroviral drugs for treatment of human deficiency virus (HIV) infection. Pharmacokinetics (pk) means how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body.


Condition Intervention Phase
Hepatitis C Virus
Drug: TMC435
Drug: TDF
Drug: TMC435 + TDF
Drug: TMC435 + TMC278
Drug: TMC278
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, 2-panel, Open-label, Randomized, Cross-over Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and Antiretroviral Agents, TMC278 and Tenofovir Disoproxil Fumarate (TDF), at Steady State

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Rate and extent of absorption of TMC435 following co-administration with TMC278 under fed condition, and vice versa. [ Time Frame: Measured on Day1, 9, 10, 11 and 12 per treatment in Panel 1. ] [ Designated as safety issue: No ]
  • Rate and extent of absorption of TMC435 following co-administration with TDF under fed condition, and vice versa. [ Time Frame: Measured on Day1, 5, 6, 7 and 8 per treatment in Panel 2. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability following co-administration of TMC435 and TMC278 (Panel 1) [ Time Frame: 89 to 94 days (till and including last safety follow-up visit) for Panel 1 ] [ Designated as safety issue: No ]
  • Safety and tolerability following co-administration of TMC435 and TDF (Panel 2) [ Time Frame: 63 to 68 days (till and including last safety follow-up visit) for Panel 2 ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
TMC435 150 mg capsule once daily for 11 days
Drug: TMC435
150 mg capsule once daily for 11 days
Experimental: 002
TMC278 25 mg tablet once daily for 11 days
Drug: TMC278
25 mg tablet once daily for 11 days
Experimental: 003
TMC435 + TMC278 150 mg TMC435 capsule + 25 mg TMC278 tablet once daily for 11 days
Drug: TMC435 + TMC278
150 mg TMC435 capsule + 25 mg TMC278 tablet, once daily for 11 days
Experimental: 004
TMC435 150 mg capsule once daily for 7 days
Drug: TMC435
150 mg capsule once daily for 7 days
Experimental: 005
TDF 300 mg tablet once daily for 7 days
Drug: TDF
300 mg tablet once daily for 7 days
Experimental: 006
TMC435 + TDF 150 mg TMC435 capsule + 300 mg TDF tablet once daily for 7 days
Drug: TMC435 + TDF
150 mg TMC435 capsule + 300 mg TDF tablet, once daily for 7 days

Detailed Description:

TMC435 is being investigated for treatment of chronic HCV infection, in combination with Peg-IFN (pegylated interferon) and RBV (ribavirin). About 30% of all HIV infected patients are co-infected with HCV and need treatment for both infections. The results of this study will provide dosing recommendations for coadministration of TMC435 and TMC278 or Tenofovir in HCV-HCV co-infected patients. This is a Phase I, open-label (both participant and investigator know the name of the medication given at certain moment), randomized (sequence of treatment with study medications is assigned by chance), crossover trial in 48 healthy participants to investigate the pharmacokinetic interaction between TMC435 and an antiretroviral agent (TMC278 or tenofovir), at steady state. The participants are being allocated to one of two panels. In Panel 1, participants will receive three treatments (treatment A-B-C) in a randomized order. Participants will receive TMC435 150 mg q.d., TMC278 25 mg q.d.and TMC278 25 mg q.d. + TMC435 150 mg q.d., respectively. All treatments will be administered for 11 days and with food. There will be a washout period (a period where no study drug will be taken in view of having all the medication eliminated from the body before starting a new treatment) of at least 14 days between last intake of study medication in one session and first intake of study medication in the subsequent session. In Panel 2, participants will receive three treatments (treatment D-E-F) in a randomized order. Participants will receive TMC435 150 mg q.d., TDF 300 mg q.d. and TDF 300 mg q.d. + TMC435 150 mg q.d., respectively. All treatments will be administered for 7 days and with food. There will be a washout period of at least 7 days. Pharmacokinetic profiles of all three compounds will be determined through blood samples taken at regular intervals during the study. Safety and tolerability will be assessed during the study period and in follow-up. Blood and urine samples, electrocardiogram (ECG) and vital signs (blood pressure and heart rate) will be taken at screening, before medication intake on days 1 and 11 and on Day 12 in each session of Panel 1, before medication intake on days 1 and 7 and on Day 8 in each session of Panel 2, 5 hours post dose on Day11 and Day 7 in Panel 1 and 2, respectively and at the 2 follow up visits at 1 week and 4-5 weeks after last dose of study medication in the last session. A physical examination will be performed at screening, on day -1 (= day before first medication intake in each session for both panels) and during the 2 follow up visits. Each volunteer will receive 3 treatments for 11 or 7 days (Panel 1 and 2, respectively), minimum 14 or 7 days apart from each other (Panel 1 and 2, respectively). Volunteers in Panel 1 will take oral TMC435 150 mg q.d., oral TMC278 25 mg q.d. and combined. Volunteers in Panel 2 will take oral TMC435 150 mg q.d., oral TDF 300 mg q.d. and combined.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • No-smoker for at least 3 months
  • Body Mass Index of 18.0 to 30.0 kg/m2
  • Healthy based on a medical evaluation including medical history, physical examination, blood tests and electrocardiogram

Exclusion Criteria:

  • Infection with Hepatitis A, B or C Virus
  • Infection with the Human Immunodeficiency Virus (HIV)
  • History of, or any current medical condition which could impact the safety of the participant in the study
  • Having previously participated in a multiple-dose trial with TMC435 and/or TMC278, or in a single- or multiple-dose trial with TMC278 long-acting
  • Having previously participated in more than 3 single-dose trials with TMC435 and/or TMC278.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01205139

Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT01205139     History of Changes
Other Study ID Numbers: CR017392
Study First Received: September 16, 2010
Last Updated: November 23, 2012
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
TMC435-TiDP16-C114
TMC435-C114
TMC435
HCV
Hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Tenofovir
Tenofovir disoproxil
Anti-Retroviral Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 16, 2014