TMC435-TiDP16-C108 - A Study in Healthy Volunteers Investigating the Pharmacokinetic Interaction Between TMC435 and Digoxin and Between TMC435 and Rosuvastatin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT01288742
First received: January 20, 2011
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to investigate the effect of steady-state concentrations of TMC435 on the single-dose pharmacokinetics of digoxin or rosuvastatin , and the effect of a single dose of digoxin or rosuvastatin on the steady-state pharmacokinetics of TMC435. Steady state is a term that 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. 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: Rosuvastatin
Drug: TMC435
Drug: Digoxin
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, Crossover Trial in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and Transporter Substrates, Digoxin and Rosuvastatin

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Change in absorption of TMC435 following co-administration with Digoxin (Panel 1). [ Time Frame: Measured on Days 1, 5-11 (Trt B). Reference for TMC435 is from historical data. ] [ Designated as safety issue: No ]
  • Change in absorption of Digoxin following co-administration with TMC435 (Panel 1). [ Time Frame: Measured on Day 7-11 (Trt B). Reference for Digoxin is on Day 1-5 of Trt A. ] [ Designated as safety issue: No ]
  • Change in absorption of TMC435 following co-administration with rosuvastatin (Panel 2). [ Time Frame: Measured on Day 1, 5-11 (Trt D). Reference for TMC435 are historical data. ] [ Designated as safety issue: No ]
  • Change in absorption of rosuvastatin following co-administration with TMC435 (Panel 2). [ Time Frame: Measured on Day 7-11 (Trt D). Reference for rosuvastatin is on Days 1-5 of Trt C. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability - TMC435 and Digoxin [ Time Frame: 51 to 56 days (until and including last safety follow-up visit) for Panel 1 ] [ Designated as safety issue: Yes ]
  • Number of participants with adverse events as a measure of safety and tolerability - TMC435 and rosuvastatin [ Time Frame: 51 to 56 days (until and including last safety follow-up visit) for Panel 2 ] [ Designated as safety issue: Yes ]

Enrollment: 33
Study Start Date: January 2011
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
TMC435 One 150-mg capsule once daily for 7 days (Trts B and D).
Drug: TMC435
One 150-mg capsule once daily for 7 days (Trts B and D).
Experimental: 002
Digoxin One 0.25-mg tablet for 1 day (Trt A)
Drug: Digoxin
One 0.25-mg tablet for 1 day (Trt A)
Experimental: 003
Digoxin One 0.25-mg tablet together with 1 capsule of TMC435 (150 mg) on Day 7 of Trt B.
Drug: Digoxin
One 0.25-mg tablet together with 1 capsule of TMC435 (150 mg) on Day 7 of Trt B.
Experimental: 004
Rosuvastatin One 10-mg tablet for 1 day (Trt C).
Drug: Rosuvastatin
One 10-mg tablet for 1 day (Trt C).
Experimental: 005
Rosuvastatin One 10-mg tablet together with 1 capsule of TMC435 (150 mg) on Day 7 of Trt D.
Drug: Rosuvastatin
One 10-mg tablet together with 1 capsule of TMC435 (150 mg) on Day 7 of Trt D.

Detailed Description:

TMC435 is being investigated for treatment of chronic hepatitis C virus (HCV) infection, in combination with Peg-IFN (pegylated interferon) and RBV (ribavirin). Digoxin and rosuvastatin are expressed in the liver and intestine and mediate the transport of drugs out of the blood circulation. The result of this study will provide dosing recommendations for TMC435 and for digoxin, rosuvastatin, or other substrates using the same drug transporter molecules, when being coadministered. 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 32 healthy volunteers to investigate the pharmacokinetic interaction between TMC435, at steady state, and digoxin or rosuvastatin at a single dose. The volunteers will be allocated to one of two panels. In Panel 1, volunteers will receive two treatments (Trts A and B) in a randomized order. Volunteers will receive digoxin 0.25 mg once daily for 1 day (Trt A) and TMC435 150 mg once daily for 7 days (Trt B) and 0.25 mg digoxin once daily for 1 day (Trt B). In Panel 2, volunteers will receive two treatments (Trts C and D) in a randomized order. Volunteers will receive rosuvastatin 10 mg once daily for 1 day (Trt C) and TMC435 150 mg once daily for 7 days (Trt D) and rosuvastatin 10 mg once daily for 1 day (Trt D). In both panels, there will be a washout period (a period when no study drug will be taken, in order to have all the medication eliminated from the body before starting a new treatment) of at least 14 days between last intake of the study medication in one session and the first intake of study medication in the subsequent session. 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 during 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 Day -1 or Day 1 (Trts A, B, C, and D), on Day 2 (Trts A and C), before medication intake and 6 hours postdose (only vital signs and ECG) on Day 7 (Trts B and D), on Day 8 (Trts B and D) 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 on Day 2 in Trts A and C, on Day -1 and on Day 8 of Trts B and D and during the 2 follow-up visits. Each volunteer is part of one panel and follows 2 treatment (Trt) periods, which are a minimum 14 days apart from each other. Trt period for Trts A and C - 5 days; Trt period for Trts B and D - 11 days. Trt A and B = Panel 1, Trt C and D = Panel 2. A single, oral dose of digoxin (0.25 mg) or rosuvastatin (10 mg) to be given in Trt A or Trt C, respectively. Multiple doses of TMC435 (150 mg) for 7 days to be given in TrtB and D, with a single dose of digoxin or rosuvastatin on Day7, respectively.

  Eligibility

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

Inclusion Criteria:

  • Non-smoker or not having chewed tobacco for at least 6 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, vital signs, 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
  • Having previously participated in more than 3 single-dose trials with TMC435
  • History of rhabdomyolysis or other muscle abnormalities upon statin intake (Panel 2).
  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: NCT01288742

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: NCT01288742     History of Changes
Other Study ID Numbers: CR017770, TMC435-TiDP16-C108
Study First Received: January 20, 2011
Last Updated: November 29, 2012
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
TMC435-TiDP16-C108
TMC435-C108
TMC435
HPC
HCV
Hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Digoxin
Rosuvastatin
Anti-Arrhythmia Agents
Anticholesteremic Agents
Antimetabolites
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014