search
Back to results

Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvir (MK-8408) in Participants With Hepatitis C Infection (MK-8408-003)

Primary Purpose

Hepatitis C Infection

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ruzasvir
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C Infection

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Body mass index (BMI) >=18 to<=37 kg/m^2
  • In general good health, except for HCV infection
  • Clinical diagnosis of chronic HCV infection exclusively GT3 (Panels A-D) or exclusively GT1a (Panels E-F), or exclusively GT2b (Panels G-H).
  • Must agree to follow the smoking restrictions defined by the CRU
  • Must agree to use an acceptable method of contraception during the study and for 90 days after the last dose of ruzasvir

Exclusion Criteria:

  • Clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
  • History of clinically significant hepatic disease, Gilbert's disease or biliary tract disease
  • History of cancer (malignancy) with the exception of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or successfully-treated malignancies ≥10 years prior to screening
  • History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
  • Positive for hepatitis B or human immunodeficiency virus (HIV)
  • Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
  • Participated in another investigational trial within 4 weeks prior to the screening visit
  • QTc interval >=470 msec (for males) or >= 480 msec (for females)
  • Unable to refrain from or anticipates use of any medication (prescription and/or non-prescription) or herbal remedies beginning approximately 2 weeks prior to first study drug dose, throughout the trial until the post-trial visit
  • Consumes >2 glasses of alcoholic beverages per day
  • Regular user (including "recreational use") of any illicit drugs or history of drug (including alcohol) abuse within approximately 12 months
  • Evidence or history of chronic hepatitis not caused by HCV
  • Previous treatment with other HCV NS5A inhibitors such as MK-8742, daclatasvir, or MK-8325
  • Treatment with other HCV therapies such as the HCV protease
  • Evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score >=3)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Part I GT3 Participants

    Part II GT1a Participants

    Part III GT2b Participants

    Arm Description

    Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

    Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

    Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.

    Outcomes

    Primary Outcome Measures

    Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline
    Blood was collected at baseline and on Days 1, 2, 3, 4 and 5 to determine HCV RNA levels. Least squares means (LSM) and confidence intervals (CI) were obtained from an analysis of variance (ANOVA) model with maximum log10 HCV RNA change from baseline as response and a fixed effect for treatment. The primary hypothesis was that the mean change from baseline would be a reduction of ≥3 log10. A positive change from baseline indicates a reduction from baseline in log10 HCV RNA.
    Number of Participants Who Experienced One or More Adverse Events (AEs)
    An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
    Number of Participants Who Discontinued Study Drug Due To An AE
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

    Secondary Outcome Measures

    Full Information

    First Posted
    February 27, 2014
    Last Updated
    December 3, 2018
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02076100
    Brief Title
    Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvir (MK-8408) in Participants With Hepatitis C Infection (MK-8408-003)
    Official Title
    A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-8408 in Subjects With Hepatitis C Infection
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    March 27, 2014 (Actual)
    Primary Completion Date
    November 15, 2015 (Actual)
    Study Completion Date
    November 15, 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a 3-part study of Ruzasvir (MK-8408) for participants with hepatitis C infection. Successive participants will be enrolled as dose levels are evaluated to find the maximum safe and well tolerated dose of Ruzasvir. Part I will be for participants with hepatitis C virus (HCV) genotype 3 (GT3) and will run first: Part II will be for participants with HCV genotype 1a (GT1a), and Part III will be for participants with HCV genotype 2b (GT2b). Parts II and III may run concurrently. The primary study hypothesis is that a safe and tolerable dose of Ruzasvir that reduces viral load will be found to support further clinical investigation.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis C Infection

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    22 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Part I GT3 Participants
    Arm Type
    Experimental
    Arm Description
    Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.
    Arm Title
    Part II GT1a Participants
    Arm Type
    Experimental
    Arm Description
    Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.
    Arm Title
    Part III GT2b Participants
    Arm Type
    Experimental
    Arm Description
    Participants receive Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.
    Intervention Type
    Drug
    Intervention Name(s)
    Ruzasvir
    Other Intervention Name(s)
    MK-8408
    Intervention Description
    Ruzasvir capsules, orally, starting at a dose of 60 mg once per day (QD) x 5 days with doses increasing or decreasing as clinically indicated.
    Primary Outcome Measure Information:
    Title
    Maximum log10 HCV Ribonucleic Acid (RNA) Change From Baseline
    Description
    Blood was collected at baseline and on Days 1, 2, 3, 4 and 5 to determine HCV RNA levels. Least squares means (LSM) and confidence intervals (CI) were obtained from an analysis of variance (ANOVA) model with maximum log10 HCV RNA change from baseline as response and a fixed effect for treatment. The primary hypothesis was that the mean change from baseline would be a reduction of ≥3 log10. A positive change from baseline indicates a reduction from baseline in log10 HCV RNA.
    Time Frame
    Baseline and up to Day 5
    Title
    Number of Participants Who Experienced One or More Adverse Events (AEs)
    Description
    An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
    Time Frame
    Up to 61 days
    Title
    Number of Participants Who Discontinued Study Drug Due To An AE
    Description
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
    Time Frame
    Up to 5 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Body mass index (BMI) >=18 to<=37 kg/m^2 In general good health, except for HCV infection Clinical diagnosis of chronic HCV infection exclusively GT3 (Panels A-D) or exclusively GT1a (Panels E-F), or exclusively GT2b (Panels G-H). Must agree to follow the smoking restrictions defined by the CRU Must agree to use an acceptable method of contraception during the study and for 90 days after the last dose of ruzasvir Exclusion Criteria: Clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases History of clinically significant hepatic disease, Gilbert's disease or biliary tract disease History of cancer (malignancy) with the exception of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or successfully-treated malignancies ≥10 years prior to screening History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food Positive for hepatitis B or human immunodeficiency virus (HIV) Major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening Participated in another investigational trial within 4 weeks prior to the screening visit QTc interval >=470 msec (for males) or >= 480 msec (for females) Unable to refrain from or anticipates use of any medication (prescription and/or non-prescription) or herbal remedies beginning approximately 2 weeks prior to first study drug dose, throughout the trial until the post-trial visit Consumes >2 glasses of alcoholic beverages per day Regular user (including "recreational use") of any illicit drugs or history of drug (including alcohol) abuse within approximately 12 months Evidence or history of chronic hepatitis not caused by HCV Previous treatment with other HCV NS5A inhibitors such as MK-8742, daclatasvir, or MK-8325 Treatment with other HCV therapies such as the HCV protease Evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score >=3)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php

    Learn more about this trial

    Safety, Pharmacokinetics, and Pharmacodynamics of Ruzasvir (MK-8408) in Participants With Hepatitis C Infection (MK-8408-003)

    We'll reach out to this number within 24 hrs