TMC435350-TiDP16-C105: Phase I, 3-way Crossover, Drug-drug Interaction Between TMC435350 and Rifampin After Multiple Dosing.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00741169
First received: August 22, 2008
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to assess the interactions seen when somebody doses with TMC435350 and Rifampin (commercial form of antibiotic).


Condition Intervention Phase
Hepatitis C
HCV
Tuberculosis
Rifampin
Pharmacokinetics
Drug: TMC435350
Drug: Rifampin
Drug: TMC435350+rifampin
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: Phase I, Open-label, 3-way Crossover Trial in Healthy Volunteers to Determine the Drug-drug Interaction Between TMC435350 and Rifampin After Multiple Dosing.

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Pharmacokinetic (PK) profile of TMC435350 [ Time Frame: On Day 1, 2, 4, 6, and 7 of Treatments A and C ] [ Designated as safety issue: No ]
    The following PK parameters will be assessed: C0h on Day 7 of Treatments A and C; and C0h, Cmin, Cmax, tmax, AUC24h, Css,av, FI, λz, t1/2term, Ratio Cmin test/ref, Ratio C0h test/ref, Ratio Cmax test/ref, and Ratio AUC24h test/ref.

  • Pharmacokinetic (PK) profile of rifampin and 25-deacetylrifampin [ Time Frame: On Day 1, 2, 4, 6, and 7 of Treatments B and C ] [ Designated as safety issue: No ]
    The PK parameter of C0h will be assessed on Day 1, 2, 4 and 6 of Treatments B and C, and the PK parameters of C0h, Cmin, Cmax, tmax, AUC24h, Css,av, FI, λz, t1/2term, Ratio Cmin test/ref, Ratio C0h test/ref , Ratio Cmax test/ref , Ratio AUC24h test/ref on Day 7 of Treatments B and C.


Secondary Outcome Measures:
  • The number of participants reporting adverse events as a measure of safety and tolerability. [ Time Frame: Up to 30 to 35 days after the last intake of study drug. ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: June 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Sequence ABC
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence will consist of Treatment A (TMC435350 200 mg once daily for 7 days), Treatment B (rifampin 600 mg once daily for 7 days), and Treatment C (TMC435350 200 mg once daily+rifampin 600 mg once daily for 7 days). Participants will receive 1 treatment (A, B, or C) during each treatment session. There will be 3 treatment sessions, each treatment session will be separated by 10 days.
Drug: TMC435350
200 mg taken by mouth once daily for 7 days
Drug: Rifampin
600 mg taken by mouth once daily for 7 days
Drug: TMC435350+rifampin
The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.
Experimental: Treatment Sequence BCA Drug: TMC435350
200 mg taken by mouth once daily for 7 days
Drug: Rifampin
600 mg taken by mouth once daily for 7 days
Drug: TMC435350+rifampin
The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.
Experimental: Treatment Sequence CAB Drug: TMC435350
200 mg taken by mouth once daily for 7 days
Drug: Rifampin
600 mg taken by mouth once daily for 7 days
Drug: TMC435350+rifampin
The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.
Experimental: Treatment sequence CBA Drug: TMC435350
200 mg taken by mouth once daily for 7 days
Drug: Rifampin
600 mg taken by mouth once daily for 7 days
Drug: TMC435350+rifampin
The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.
Experimental: Treatment Sequence BAC Drug: TMC435350
200 mg taken by mouth once daily for 7 days
Drug: Rifampin
600 mg taken by mouth once daily for 7 days
Drug: TMC435350+rifampin
The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.
Experimental: Treatment Sequence ACB Drug: TMC435350
200 mg taken by mouth once daily for 7 days
Drug: Rifampin
600 mg taken by mouth once daily for 7 days
Drug: TMC435350+rifampin
The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.

Detailed Description:

This is a Phase I, open-label, randomized, 3-way crossover trial in 18 healthy volunteers to investigate the potential drug-drug interaction between rifampin and TMC435350. TMC435350 is a protease inhibitor in development for treatment of chronic HCV infection. The goal is to assess the PK and safety data generated during 3 in-patients sessions. At each session the volunteer will receive one of 3 treatments. Rifampin is a medication commonly given to patients with Mycobacterium infections such as tuberculosis. Some patients have both chronic HCV and tuberculosis, therefore it is necessary to know how the medications will affect each other when they are taken together. Treatment A: TMC435350 200 mg q.d. for 7 days. Treatment B: rifampin 600 mg q.d. for 7 days. Treatment C: the combination of TMC435350 200 mg q.d. + rifampin 600 mg q.d. for 7 days. There will be a washout period of at least 10 days between subsequent sessions. Day 8 of a treatment session is the first day of the washout period. Full pharmacokinetic profiles of TMC435350 will be determined on Day 7 of Treatments A and C. Full pharmacokinetic profiles of rifampin and its active metabolite 25-deacetyl rifampin will be determined on Day 7 of Treatments B and C. Safety and tolerability will be monitored continuously throughout the trial. Volunteers will receive the dose regimens in Treatments A, B, C: Treatment A: TMC435350 200 mg q.d. for 7 days. Treatment B: rifampin 600 mg q.d. for 7 days, Treatment C: the combination of TMC435350 200 mg+rifampin 600 mg both q.d. for 7 days. The volunteers will enter the testing facility the night before the first dosing in each session (on Day -1 = one day before the first dosing) and stay in the testing facility until 72 hours after the last intake of medication on Day (10).

  Eligibility

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

Inclusion Criteria:

  • Volunteers must meet all of the following inclusion criteria: Non smoking for at least 3 months prior to selection, Normal weight as defined by a body mass index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, extremes included), Informed Consent Form (ICF) signed voluntarily before the first trial related activity, Able to comply with protocol requirements, Normal 12-lead electrocardiogram (ECG) (in triplicate) at screening including: Normal sinus rhythm (heart rate [HR] between 40 and 100 bpm), QTc interval = 450 ms, QRS interval < 120 ms, PR interval = 220 ms
  • Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs, and the results of blood biochemistry, and hematology tests and a urinalysis carried out at screening.

Exclusion Criteria:

  • Past history of heart arrhythmias (extrasystole, tachycardia at rest) or having baseline prolongation of QTc interval > 450 ms
  • history of risk factors for Torsade de Pointes syndrome (hypokalemia, family history of long QT syndrome)
  • Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post tubal ligation (without reversal operation)
  • History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise subject's safety and/or compliance with the trial procedures
  • Hepatitis A, B, or C infection (confirmed by hepatitis A antibody, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) or human immunodeficiency virus - type 1 (HIV-1) or HIV-2 infection at screening
  • A positive urine drug test at screening
  • Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease
  • Currently significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability
  • Any history of significant skin disease.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00741169

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

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00741169     History of Changes
Other Study ID Numbers: CR015412
Study First Received: August 22, 2008
Last Updated: April 17, 2013
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
TMC435350-TiDP16-C105
TMC435350-C105
Hepatitis C
HCV
Rifampin

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Tuberculosis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Rifampin
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014