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

Primary Purpose

Hepatitis C, HCV, Tuberculosis

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
TMC435350
Rifampin
TMC435350+rifampin
Sponsored by
Tibotec Pharmaceuticals, Ireland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring TMC435350-TiDP16-C105, TMC435350-C105, Hepatitis C, HCV, Rifampin

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Treatment Sequence ABC

    Treatment Sequence BCA

    Treatment Sequence CAB

    Treatment sequence CBA

    Treatment Sequence BAC

    Treatment Sequence ACB

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    Pharmacokinetic (PK) profile of TMC435350
    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
    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.

    Full Information

    First Posted
    August 22, 2008
    Last Updated
    April 17, 2013
    Sponsor
    Tibotec Pharmaceuticals, Ireland
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00741169
    Brief Title
    TMC435350-TiDP16-C105: Phase I, 3-way Crossover, Drug-drug Interaction Between TMC435350 and Rifampin After Multiple Dosing.
    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.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2013
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2008 (undefined)
    Primary Completion Date
    December 2008 (Actual)
    Study Completion Date
    December 2008 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Tibotec Pharmaceuticals, Ireland

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis C, HCV, Tuberculosis, Rifampin, Pharmacokinetics
    Keywords
    TMC435350-TiDP16-C105, TMC435350-C105, Hepatitis C, HCV, Rifampin

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Crossover Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    21 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment Sequence ABC
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Treatment Sequence BCA
    Arm Type
    Experimental
    Arm Title
    Treatment Sequence CAB
    Arm Type
    Experimental
    Arm Title
    Treatment sequence CBA
    Arm Type
    Experimental
    Arm Title
    Treatment Sequence BAC
    Arm Type
    Experimental
    Arm Title
    Treatment Sequence ACB
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    TMC435350
    Intervention Description
    200 mg taken by mouth once daily for 7 days
    Intervention Type
    Drug
    Intervention Name(s)
    Rifampin
    Intervention Description
    600 mg taken by mouth once daily for 7 days
    Intervention Type
    Drug
    Intervention Name(s)
    TMC435350+rifampin
    Intervention Description
    The combination of TMC435350 200 mg + rifampin 600 mg both taken by mouth once daily for 7 days.
    Primary Outcome Measure Information:
    Title
    Pharmacokinetic (PK) profile of TMC435350
    Description
    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.
    Time Frame
    On Day 1, 2, 4, 6, and 7 of Treatments A and C
    Title
    Pharmacokinetic (PK) profile of rifampin and 25-deacetylrifampin
    Description
    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.
    Time Frame
    On Day 1, 2, 4, 6, and 7 of Treatments B and C
    Secondary Outcome Measure Information:
    Title
    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.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Tibotec Pharmaceuticals Limited Clinical Trial
    Organizational Affiliation
    Tibotec Pharmaceutical Limited
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

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