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Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Voxilaprevir in Adults With Chronic Hepatitis C Virus Infection

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02185794
Collaborator
(none)
101
Enrollment
11
Locations
16
Arms
15.5
Actual Duration (Months)
9.2
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of voxilaprevir (formerly GS-9857) alone or with sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) and antiviral activity of voxilaprevir in adults with genotype 1, 2, 3, 4 hepatitis C virus (HCV) infection. All participants will be monitored for up to 48 weeks after the last dose.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
101 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Phase 1b, Randomized, Double-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GS-9857 in Subjects With Chronic Hepatitis C Virus Infection
Actual Study Start Date :
Jun 13, 2014
Actual Primary Completion Date :
Dec 22, 2014
Actual Study Completion Date :
Sep 28, 2015

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo (GT 1a, Cohort 1)

Participants with genotype (GT) 1a HCV infection will receive placebo once daily for 3 days under fasted conditions.

Drug: Placebo to match voxilaprevir
Placebo to match voxilaprevir tablets administered orally once daily
Experimental: Voxilaprevir 50 mg (GT 1a, Cohort 1)

Participants with GT 1a HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.

Drug: Voxilaprevir
Voxilaprevir tablets administered orally once daily
Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 100 mg (GT 1a, Cohort 1)

    Participants with GT 1a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 300 mg (GT 1a, Cohort 1)

    Participants with GT 1a HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Placebo Comparator: Placebo (GT 3, Cohort 2)

    Participants with GT 3 HCV infection will receive placebo once daily for 3 days under fasted conditions.

    Drug: Placebo to match voxilaprevir
    Placebo to match voxilaprevir tablets administered orally once daily
    Experimental: Voxilaprevir 50 mg (GT 3, Cohort 2)

    Participants with GT 3 HCV infection will receive voxilaprevir 50 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 100 mg (GT 3, Cohort 2)

    Participants with GT 3 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 300 mg (GT 3, Cohort 2)

    Participants with GT 3 HCV infection will receive voxilaprevir 300 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Placebo Comparator: Placebo (GT 2, Cohort 3)

    Participants with GT 2 HCV infection will receive placebo once daily for 3 days under fasted conditions.

    Drug: Placebo to match voxilaprevir
    Placebo to match voxilaprevir tablets administered orally once daily
    Experimental: Voxilaprevir 100 mg (GT 2, Cohort 3)

    Participants with GT 2 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 100 mg (GT 4, Cohort 4)

    Participants with GT 4 HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 100 mg (GT 1b, Cohort 5)

    Participants with GT 1b HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fasted conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)

    Participants with GT 3a HCV infection will receive voxilaprevir 100 mg once daily for 3 days under fed conditions.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 600 mg (Cohorts 7-9)

    Participants with genotypes 1a, 1b, 2, 3, or 4 HCV infection will receive voxilaprevir up to 600 mg under fasted or fed conditions for 3 days.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    		•
    Experimental: Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 1, Cohort 10)

    Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 after moderate fat meal and voxilaprevir 100 mg plus sofosbuvir (SOF)/velpatasvir (VEL) (400/100 mg) fixed-dose combination (FDC)on Days 2 and 3 after either a light or moderate-fat meal.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    • Drug: SOF/VEL
    400 mg/100 mg FDC tablet administered orally once daily
    Experimental: Voxilaprevir 100 mg + SOF/VEL 400/100 mg (Group 2, Cohort 10)

    Participants with any GT HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal.

    Drug: Voxilaprevir
    Voxilaprevir tablets administered orally once daily
    Other Names:
  • GS-9857

    • Drug: SOF/VEL
    400 mg/100 mg FDC tablet administered orally once daily

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Experiencing Treatment Emergent Adverse Events [First dose date up to Day 3 plus 30 days]

    2. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities [First dose date up to Day 3 plus 30 days]

      Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant.

    3. Antiviral Activity of Voxilaprevir as Measured by Change From Baseline in Plasma HCV RNA [Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48]

      The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6). Data are summarized by treatment/cohort and placebo.

    Secondary Outcome Measures

    1. Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48 [Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48]

      The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).

    2. Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA [Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48]

      Categorical declines from baseline were summarized by the number of participants with a < 1, ≥ 1 to <2, ≥ 2 to <3, or ≥ 3 log10 IU/mL decrease in HCV RNA from baseline to each postdose assessment up to Week 48 by treatment/cohort and placebo. The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).

    3. Percentage of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected, and < LLOQ Target Not Detected (TND) [Days 4, 5, 6, 7, 8, 10, and Week 48]

      The lower limit of quantitation (LLOQ) detection for HCV RNA levels was 15 IU/mL. HCV detected means calculated HCV RNA level is below LLOQ of the assay. The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Chronic genotype 1-4 HCV infection

    • For Cohorts 1-9, HCV RNA ≥ 100,000 IU/mL at screening (no HCV RNA restriction for Cohort 10)

    • Screening laboratory values within defined thresholds

    • Use of two effective contraception methods if female of childbearing potential or sexually active male

    Key Exclusion Criteria:

    • Pregnant or nursing female or male with pregnant female partner

    • Presence of cirrhosis

    • Prior exposure to approved or experimental HCV Protease Inhibitors

    • Co-infection with HIV or hepatitis B virus (HBV)

    • Current or prior history of clinical hepatic decompensation

    • Chronic use of systemic immunosuppressive agents

    • History of clinically significant illness or any other medical disorder that may interfere with participant's treatment, assessment or compliance with the protocol

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Costa Mesa California United States
    2 DeLand Florida United States
    3 Orlando Florida United States
    4 Kansas City Missouri United States
    5 Saint Louis Missouri United States
    6 Berlin New Jersey United States
    7 Marlton New Jersey United States
    8 Philadelphia Pennsylvania United States
    9 Knoxville Tennessee United States
    10 San Antonio Texas United States
    11 San Juan Puerto Rico

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02185794
    Other Study ID Numbers:
    • GS-US-338-1121
    First Posted:
    Jul 10, 2014
    Last Update Posted:
    Sep 17, 2020
    Last Verified:
    Aug 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    Sustained Virologic Response
    Direct Acting Antiviral
    Combination Therapy
    Liver Diseases
    Digestive System Diseases
    Hepatitis, Viral, Human
    Enterovirus Infections
    Picornaviridae Infections
    RNA Virus Infections
    Flaviviridae Infections
    Antiviral Agents
    Anti-Infective Agents
    Therapeutic Uses
    Pharmacologic Actions
    Antimetabolites
    Molecular Mechanisms of Pharmacological Action
    Additional relevant MeSH terms:
    Infections
    Communicable Diseases
    Hepatitis A
    Virus Diseases
    Hepatitis C
    Hepatitis C, Chronic
    Hepatitis

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in United States and Puerto Rico. The first participant was screened on 13 June 2014. The last study visit occurred on 28 September 2015.
    Pre-assignment Detail Participants were enrolled in Cohorts 1, 2, 3, 4, 5, 6 and 10. Cohorts 7, 8, and 9 were not conducted.
    Arm/Group Title Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg
    Arm/Group Description Participants with HCV infection received placebo once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2 and 3. Participants with HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus sofosbuvir (SOF)/velpatasvir (VEL) (400/100 mg) fixed-dose combination (FDC) on Days 2 and 3 after moderate fat or light meal. This arm was part of cohort 10.
    Period Title: Overall Study
    STARTED 9 20 33 16 7 16
    COMPLETED 4 7 17 8 4 0
    NOT COMPLETED 5 13 16 8 3 16

    Baseline Characteristics

    Arm/Group Title Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg Total
    Arm/Group Description Participants with HCV infection received placebo once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2 and 3. Participants with HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal. This arm was part of cohort 10. Total of all reporting groups
    Overall Participants 8 14 30 15 6 16 89
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52
    (6.1)
    49
    (7.7)
    52
    (8.0)
    43
    (9.4)
    51
    (6.2)
    56
    (5.2)
    51
    (8.4)
    Sex: Female, Male (Count of Participants)
    Female
    1
    12.5%
    5
    35.7%
    9
    30%
    5
    33.3%
    2
    33.3%
    7
    43.8%
    29
    32.6%
    Male
    7
    87.5%
    9
    64.3%
    21
    70%
    10
    66.7%
    4
    66.7%
    9
    56.3%
    60
    67.4%
    Race/Ethnicity, Customized (Count of Participants)
    Black or African American
    2
    25%
    4
    28.6%
    12
    40%
    3
    20%
    1
    16.7%
    0
    0%
    22
    24.7%
    White
    6
    75%
    10
    71.4%
    18
    60%
    12
    80%
    5
    83.3%
    16
    100%
    67
    75.3%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    2
    25%
    7
    50%
    12
    40%
    8
    53.3%
    6
    100%
    9
    56.3%
    44
    49.4%
    Not Hispanic or Latino
    6
    75%
    7
    50%
    18
    60%
    7
    46.7%
    0
    0%
    7
    43.8%
    45
    50.6%
    HCV Genotype (Count of Participants)
    1a
    4
    50%
    8
    57.1%
    8
    26.7%
    8
    53.3%
    0
    0%
    9
    56.3%
    37
    41.6%
    1b
    0
    0%
    0
    0%
    6
    20%
    0
    0%
    0
    0%
    3
    18.8%
    9
    10.1%
    2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    1
    1.1%
    2a/2c
    0
    0%
    0
    0%
    2
    6.7%
    0
    0%
    0
    0%
    0
    0%
    2
    2.2%
    2b
    2
    25%
    0
    0%
    4
    13.3%
    0
    0%
    0
    0%
    2
    12.5%
    8
    9%
    3a
    2
    25%
    6
    42.9%
    6
    20%
    7
    46.7%
    6
    100%
    1
    6.3%
    28
    31.5%
    4
    0
    0%
    0
    0%
    2
    6.7%
    0
    0%
    0
    0%
    0
    0%
    2
    2.2%
    4a/4c/4d
    0
    0%
    0
    0%
    2
    6.7%
    0
    0%
    0
    0%
    0
    0%
    2
    2.2%
    HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 IU/mL]
    6.6
    (0.39)
    6.0
    (0.64)
    6.4
    (0.53)
    6.0
    (0.64)
    6.0
    (0.87)
    6.2
    (0.83)
    6.2
    (0.65)
    HCV RNA Category (Count of Participants)
    < 800,000 IU/mL
    1
    12.5%
    7
    50%
    6
    20%
    6
    40%
    4
    66.7%
    4
    25%
    28
    31.5%
    ≥ 800,000 IU/mL
    7
    87.5%
    7
    50%
    24
    80%
    9
    60%
    2
    33.3%
    12
    75%
    61
    68.5%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Experiencing Treatment Emergent Adverse Events
    Description
    Time Frame First dose date up to Day 3 plus 30 days

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug (voxilaprevir or placebo). Data were summarized by dose.
    Arm/Group Title Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg
    Arm/Group Description Participants with HCV infection received placebo once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, and 3. Participants with HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal. This arm was part of cohort 10.
    Measure Participants 8 14 30 15 6 16
    Number [percentage of participants]
    25.0
    312.5%
    14.3
    102.1%
    16.7
    55.7%
    13.3
    88.7%
    33.3
    555%
    12.5
    78.1%
    2. Primary Outcome
    Title Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
    Description Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant.
    Time Frame First dose date up to Day 3 plus 30 days

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set were analyzed. Data were summarized by dose.
    Arm/Group Title Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg
    Arm/Group Description Participants with HCV infection received placebo once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, and 3. Participants with HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal. This arm was part of cohort 10.
    Measure Participants 8 14 30 15 6 16
    Grade 1
    37.5
    468.8%
    28.6
    204.3%
    26.7
    89%
    20.0
    133.3%
    50.0
    833.3%
    62.5
    390.6%
    Grade 2
    25.0
    312.5%
    28.6
    204.3%
    33.3
    111%
    13.3
    88.7%
    0
    0%
    12.5
    78.1%
    Grade 3
    0
    0%
    14.3
    102.1%
    10.0
    33.3%
    26.7
    178%
    33.3
    555%
    0
    0%
    Grade 4
    0
    0%
    0
    0%
    3.3
    11%
    0
    0%
    0
    0%
    0
    0%
    3. Primary Outcome
    Title Antiviral Activity of Voxilaprevir as Measured by Change From Baseline in Plasma HCV RNA
    Description The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6). Data are summarized by treatment/cohort and placebo.
    Time Frame Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48

    Outcome Measure Data

    Analysis Population Description
    The Efficacy Analysis Set included all enrolled participants with appropriate genotype who received at least one dose of the study drug (voxilaprevir or placebo) and with at least one on-treatment HCV RNA assessment. Participants in the Efficacy Analysis Set with available data were analyzed.
    Arm/Group Title Placebo (GT 1a, Cohort 1) Voxilaprevir 50 mg (GT 1a, Cohort 1) Voxilaprevir 100 mg (GT 1a, Cohort 1) Voxilaprevir 300 mg (GT 1a, Cohort 1) Placebo (GT 3, Cohort 2) Voxilaprevir 50 mg (GT 3, Cohort 2) Voxilaprevir 100 mg (GT 3, Cohort 2) Voxilaprevir 300 mg (GT 3, Cohort 2) Placebo (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 4, Cohort 4) Voxilaprevir 100 mg (GT 1b, Cohort 5) Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)
    Arm/Group Description Participants with genotype (GT) 1a HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 4 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1b HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3a HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions.
    Measure Participants 4 8 8 8 2 6 6 7 2 6 4 6 6
    Change at Day 4
    -0.12
    (0.136)
    -3.81
    (0.516)
    -3.97
    (0.608)
    -3.33
    (0.902)
    -0.24
    (0.813)
    -1.47
    (0.416)
    -3.20
    (0.364)
    -3.57
    (0.483)
    0.00
    (0.104)
    -3.41
    (0.444)
    -3.50
    (0.677)
    -3.57
    (0.227)
    -3.06
    (0.752)
    Change at Day 5
    -0.20
    (0.519)
    -3.58
    (1.104)
    -4.03
    (0.594)
    -3.37
    (0.894)
    -0.17
    (0.285)
    -1.43
    (0.606)
    -3.00
    (0.470)
    -3.28
    (0.515)
    -0.12
    (0.151)
    -3.37
    (0.480)
    -3.61
    (0.702)
    -3.60
    (0.390)
    -2.45
    (0.664)
    Change at Day 6
    -0.21
    (0.479)
    -3.45
    (0.829)
    -3.78
    (0.710)
    -3.47
    (0.763)
    -0.06
    (0.051)
    -1.06
    (0.632)
    -2.52
    (0.739)
    -3.13
    (0.736)
    -0.04
    (0.139)
    -3.22
    (0.689)
    -3.69
    (0.879)
    -3.61
    (0.601)
    -2.04
    (0.706)
    Change at Day 7
    0.01
    (0.340)
    -3.15
    (0.973)
    -3.88
    (0.729)
    -3.48
    (0.695)
    0.02
    (0.089)
    -0.76
    (0.352)
    -2.00
    (0.378)
    -2.89
    (0.763)
    -0.05
    (0.058)
    -2.80
    (0.494)
    -3.70
    (0.877)
    -3.42
    (0.710)
    -1.74
    (0.885)
    Change at Day 8
    0.13
    (0.260)
    -2.92
    (1.069)
    -3.54
    (0.663)
    -3.23
    (0.726)
    -0.14
    (0.158)
    -0.53
    (0.379)
    -1.79
    (0.627)
    -2.74
    (0.916)
    -0.05
    (0.090)
    -2.48
    (0.355)
    -3.53
    (0.637)
    -3.27
    (0.627)
    -1.43
    (0.987)
    Change at Day 10
    -0.06
    (0.091)
    -2.69
    (1.116)
    -3.33
    (0.756)
    -2.97
    (0.918)
    -0.23
    (0.180)
    -0.28
    (0.330)
    -1.18
    (1.055)
    -2.17
    (1.394)
    -0.13
    (0.022)
    -2.28
    (0.469)
    -3.61
    (0.674)
    -3.08
    (0.740)
    -0.62
    (1.085)
    Change at Week 48
    0.41
    (0.873)
    0.08
    (0.337)
    -0.80
    (2.094)
    -0.73
    (2.352)
    0.41
    -0.03
    (0.221)
    0.54
    0.06
    (0.370)
    -0.02
    -0.02
    0.18
    (0.247)
    -0.57
    (2.389)
    0.16
    (0.044)
    4. Secondary Outcome
    Title Antiviral Activity of Voxilaprevir as Measured by Absolute HCV RNA Level Through Week 48
    Description The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).
    Time Frame Baseline (Pre Day 1 Dose); Days 4, 5, 6, 7, 8, 10, and Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Efficacy Analysis Set with available data were analyzed. Data are summarized by treatment/cohort and placebo.
    Arm/Group Title Placebo (GT 1a, Cohort 1) Voxilaprevir 50 mg (GT 1a, Cohort 1) Voxilaprevir 100 mg (GT 1a, Cohort 1) Voxilaprevir 300 mg (GT 1a, Cohort 1) Placebo (GT 3, Cohort 2) Voxilaprevir 50 mg (GT 3, Cohort 2) Voxilaprevir 100 mg (GT 3, Cohort 2) Voxilaprevir 300 mg (GT 3, Cohort 2) Placebo (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 4, Cohort 4) Voxilaprevir 100 mg (GT 1b, Cohort 5) Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)
    Arm/Group Description Participants with GT 1a HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 4 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1b HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3a HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions.
    Measure Participants 4 8 8 8 2 6 6 7 2 6 4 6 6
    Pre Day 1 Dose
    6.73
    (0.307)
    6.30
    (0.497)
    6.35
    (0.526)
    6.05
    (0.558)
    6.11
    (0.480)
    5.61
    (0.612)
    6.75
    (0.346)
    6.01
    (0.773)
    6.71
    (0.059)
    6.24
    (0.394)
    6.16
    (0.730)
    6.23
    (0.608)
    6.01
    (0.866)
    Day 4
    6.62
    (0.378)
    2.56
    (0.705)
    2.38
    (0.759)
    2.72
    (0.943)
    5.87
    (0.332)
    4.22
    (0.878)
    3.54
    (0.455)
    2.44
    (0.693)
    6.71
    (0.164)
    2.83
    (0.611)
    2.65
    (0.533)
    2.67
    (0.500)
    2.95
    (0.505)
    Day 5
    6.53
    (0.426)
    2.73
    (1.203)
    2.33
    (0.643)
    2.67
    (0.947)
    5.94
    (0.195)
    4.19
    (1.104)
    3.75
    (0.455)
    2.73
    (0.780)
    6.59
    (0.210)
    2.87
    (0.603)
    2.55
    (0.549)
    2.63
    (0.764)
    3.56
    (0.273)
    Day 6
    6.52
    (0.320)
    2.85
    (1.000)
    2.57
    (1.028)
    2.57
    (0.818)
    6.05
    (0.532)
    4.55
    (1.203)
    4.23
    (0.604)
    2.88
    (0.882)
    6.68
    (0.199)
    3.02
    (0.754)
    2.46
    (0.300)
    2.85
    (0.685)
    3.98
    (0.413)
    Day 7
    6.74
    (0.059)
    3.15
    (1.268)
    2.47
    (0.821)
    2.56
    (0.714)
    6.13
    (0.569)
    4.85
    (0.886)
    4.75
    (0.268)
    3.12
    (0.991)
    6.67
    (0.001)
    3.44
    (0.613)
    2.45
    (0.359)
    2.82
    (1.111)
    4.27
    (0.485)
    Day 8
    6.86
    (0.144)
    3.38
    (1.019)
    2.81
    (0.901)
    2.81
    (0.671)
    5.97
    (0.323)
    5.08
    (0.655)
    4.96
    (0.531)
    3.27
    (1.100)
    6.66
    (0.031)
    3.76
    (0.497)
    2.62
    (0.278)
    2.96
    (1.111)
    4.59
    (0.528)
    Day 10
    6.68
    (0.263)
    3.61
    (1.041)
    3.03
    (0.857)
    3.07
    (0.887)
    5.88
    (0.300)
    5.43
    (0.803)
    5.56
    (0.987)
    3.83
    (1.417)
    6.58
    (0.081)
    3.96
    (0.555)
    2.54
    (0.553)
    3.15
    (1.210)
    5.40
    (0.697)
    Week 48
    6.97
    (0.488)
    6.29
    (0.825)
    5.55
    (2.007)
    5.20
    (2.085)
    6.18
    5.13
    (0.207)
    7.29
    6.38
    (1.479)
    6.65
    6.13
    6.34
    (0.696)
    5.65
    (2.473)
    5.98
    (0.891)
    5. Secondary Outcome
    Title Antiviral Activity of Voxilaprevir as Measured by Number of Participants Achieving Reductions From Baseline in HCV RNA
    Description Categorical declines from baseline were summarized by the number of participants with a < 1, ≥ 1 to <2, ≥ 2 to <3, or ≥ 3 log10 IU/mL decrease in HCV RNA from baseline to each postdose assessment up to Week 48 by treatment/cohort and placebo. The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).
    Time Frame Baseline; Days 4, 5, 6, 7, 8, 10, and Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Efficacy Analysis Set were analyzed.
    Arm/Group Title Placebo (GT 1a, Cohort 1) Voxilaprevir 50 mg (GT 1a, Cohort 1) Voxilaprevir 100 mg (GT 1a, Cohort 1) Voxilaprevir 300 mg (GT 1a, Cohort 1) Placebo (GT 3, Cohort 2) Voxilaprevir 50 mg (GT 3, Cohort 2) Voxilaprevir 100 mg (GT 3, Cohort 2) Voxilaprevir 300 mg (GT 3, Cohort 2) Placebo (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 4, Cohort 4) Voxilaprevir 100 mg (GT 1b, Cohort 5) Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)
    Arm/Group Description Participants with GT 1a HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 4 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1b HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3a HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions.
    Measure Participants 4 8 8 8 2 6 6 7 2 6 4 6 6
    Missing HCV RNA
    0
    0%
    1
    7.1%
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    1
    1.1%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    < 1 log10 IU/mL decrease in HCV RNA
    4
    50%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    0
    0%
    0
    0%
    0
    NaN
    2
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    ≥1 and <2 log10 IU/mL decrease in HCV RNA
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    4
    25%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    ≥2 and <3 log10 IU/mL decrease in HCV RNA
    0
    0%
    0
    0%
    1
    3.3%
    0
    0%
    0
    0%
    1
    6.3%
    1
    1.1%
    1
    NaN
    0
    NaN
    1
    NaN
    1
    NaN
    0
    NaN
    3
    NaN
    ≥3 log10 IU/mL decrease in HCV RNA
    0
    0%
    7
    50%
    7
    23.3%
    7
    46.7%
    0
    0%
    0
    0%
    4
    4.5%
    6
    NaN
    0
    NaN
    5
    NaN
    3
    NaN
    6
    NaN
    3
    NaN
    Missing HCV RNA
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    1
    1.1%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    < 1 log10 IU/mL decrease in HCV RNA
    4
    50%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    1
    6.3%
    0
    0%
    0
    NaN
    2
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    ≥1 and <2 log10 IU/mL decrease in HCV RNA
    0
    0%
    1
    7.1%
    0
    0%
    1
    6.7%
    0
    0%
    4
    25%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    1
    NaN
    ≥2 and <3 log10 IU/mL decrease in HCV RNA
    0
    0%
    1
    7.1%
    0
    0%
    0
    0%
    0
    0%
    1
    6.3%
    2
    2.2%
    2
    NaN
    0
    NaN
    2
    NaN
    1
    NaN
    0
    NaN
    3
    NaN
    ≥3 log10 IU/mL decrease in HCV RNA
    0
    0%
    6
    42.9%
    8
    26.7%
    6
    40%
    0
    0%
    0
    0%
    3
    3.4%
    5
    NaN
    0
    NaN
    4
    NaN
    3
    NaN
    6
    NaN
    2
    NaN
    Missing HCV RNA
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    1
    1.1%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    1
    NaN
    0
    NaN
    < 1 log10 IU/mL decrease in HCV RNA
    4
    50%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    2
    12.5%
    0
    0%
    0
    NaN
    2
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    ≥1 and <2 log10 IU/mL decrease in HCV RNA
    0
    0%
    1
    7.1%
    0
    0%
    1
    6.7%
    0
    0%
    4
    25%
    1
    1.1%
    1
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    3
    NaN
    ≥2 and <3 log10 IU/mL decrease in HCV RNA
    0
    0%
    0
    0%
    1
    3.3%
    0
    0%
    0
    0%
    0
    0%
    3
    3.4%
    1
    NaN
    0
    NaN
    2
    NaN
    1
    NaN
    1
    NaN
    2
    NaN
    ≥3 log10 IU/mL decrease in HCV RNA
    0
    0%
    7
    50%
    7
    23.3%
    6
    40%
    0
    0%
    0
    0%
    1
    1.1%
    5
    NaN
    0
    NaN
    4
    NaN
    3
    NaN
    4
    NaN
    1
    NaN
    Missing HCV RNA
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    1
    1.1%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    < 1 log10 IU/mL decrease in HCV RNA
    4
    50%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    4
    25%
    0
    0%
    0
    NaN
    2
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    1
    NaN
    ≥1 and <2 log10 IU/mL decrease in HCV RNA
    0
    0%
    2
    14.3%
    0
    0%
    0
    0%
    0
    0%
    2
    12.5%
    3
    3.4%
    1
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    2
    NaN
    ≥2 and <3 log10 IU/mL decrease in HCV RNA
    0
    0%
    0
    0%
    1
    3.3%
    1
    6.7%
    0
    0%
    0
    0%
    2
    2.2%
    2
    NaN
    0
    NaN
    3
    NaN
    1
    NaN
    2
    NaN
    3
    NaN
    ≥3 log10 IU/mL decrease in HCV RNA
    0
    0%
    6
    42.9%
    7
    23.3%
    6
    40%
    0
    0%
    0
    0%
    0
    0%
    4
    NaN
    0
    NaN
    3
    NaN
    3
    NaN
    4
    NaN
    0
    NaN
    Missing HCV RNA
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    1
    1.1%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    < 1 log10 IU/mL decrease in HCV RNA
    4
    50%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    6
    37.5%
    0
    0%
    1
    NaN
    2
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    3
    NaN
    ≥1 and <2 log10 IU/mL decrease in HCV RNA
    0
    0%
    2
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    4.5%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    2
    NaN
    ≥2 and <3 log10 IU/mL decrease in HCV RNA
    0
    0%
    2
    14.3%
    1
    3.3%
    3
    20%
    0
    0%
    0
    0%
    1
    1.1%
    2
    NaN
    0
    NaN
    6
    NaN
    1
    NaN
    2
    NaN
    1
    NaN
    ≥3 log10 IU/mL decrease in HCV RNA
    0
    0%
    4
    28.6%
    7
    23.3%
    4
    26.7%
    0
    0%
    0
    0%
    0
    0%
    4
    NaN
    0
    NaN
    0
    NaN
    3
    NaN
    4
    NaN
    0
    NaN
    Missing HCV RNA
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    1
    6.3%
    1
    1.1%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    < 1 log10 IU/mL decrease in HCV RNA
    4
    50%
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    5
    31.3%
    2
    2.2%
    1
    NaN
    2
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    4
    NaN
    ≥1 and <2 log10 IU/mL decrease in HCV RNA
    0
    0%
    3
    21.4%
    1
    3.3%
    1
    6.7%
    0
    0%
    0
    0%
    2
    2.2%
    2
    NaN
    0
    NaN
    2
    NaN
    0
    NaN
    1
    NaN
    1
    NaN
    ≥2 and <3 log10 IU/mL decrease in HCV RNA
    0
    0%
    2
    14.3%
    0
    0%
    3
    20%
    0
    0%
    0
    0%
    1
    1.1%
    1
    NaN
    0
    NaN
    4
    NaN
    0
    NaN
    1
    NaN
    1
    NaN
    ≥3 log10 IU/mL decrease in HCV RNA
    0
    0%
    3
    21.4%
    7
    23.3%
    3
    20%
    0
    0%
    0
    0%
    0
    0%
    3
    NaN
    0
    NaN
    0
    NaN
    4
    NaN
    4
    NaN
    0
    NaN
    Missing HCV RNA
    2
    25%
    4
    28.6%
    1
    3.3%
    2
    13.3%
    1
    16.7%
    3
    18.8%
    5
    5.6%
    5
    NaN
    1
    NaN
    5
    NaN
    0
    NaN
    1
    NaN
    2
    NaN
    < 1 log10 IU/mL decrease in HCV RNA
    2
    25%
    4
    28.6%
    6
    20%
    5
    33.3%
    1
    16.7%
    3
    18.8%
    1
    1.1%
    2
    NaN
    1
    NaN
    1
    NaN
    4
    NaN
    4
    NaN
    4
    NaN
    ≥1 and <2 log10 IU/mL decrease in HCV RNA
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    ≥2 and <3 log10 IU/mL decrease in HCV RNA
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    ≥3 log10 IU/mL decrease in HCV RNA
    0
    0%
    0
    0%
    1
    3.3%
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    1
    NaN
    0
    NaN
    6. Secondary Outcome
    Title Percentage of Participants Who Have HCV RNA < Lower Limit of Quantitation (LLOQ) Detected, and < LLOQ Target Not Detected (TND)
    Description The lower limit of quantitation (LLOQ) detection for HCV RNA levels was 15 IU/mL. HCV detected means calculated HCV RNA level is below LLOQ of the assay. The outcome measure was assessed to evaluate antiviral activity of voxilaprevir only (cohorts 1 through 6).
    Time Frame Days 4, 5, 6, 7, 8, 10, and Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in the Efficacy Analysis Set were analyzed. Data are summarized by treatment/cohort and placebo.
    Arm/Group Title Placebo (GT 1a, Cohort 1) Voxilaprevir 50 mg (GT 1a, Cohort 1) Voxilaprevir 100 mg (GT 1a, Cohort 1) Voxilaprevir 300 mg (GT 1a, Cohort 1) Placebo (GT 3, Cohort 2) Voxilaprevir 50 mg (GT 3, Cohort 2) Voxilaprevir 100 mg (GT 3, Cohort 2) Voxilaprevir 300 mg (GT 3, Cohort 2) Placebo (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 2, Cohort 3) Voxilaprevir 100 mg (GT 4, Cohort 4) Voxilaprevir 100 mg (GT 1b, Cohort 5) Voxilaprevir 100 mg Fed (GT 3a, Cohort 6)
    Arm/Group Description Participants with GT 1a HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1a HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3 HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received placebo once daily for 3 days under fasted conditions. Participants with GT 2 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 4 HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 1b HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. Participants with GT 3a HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions.
    Measure Participants 4 8 8 8 2 6 6 7 2 6 4 6 6
    Day 4 < LLOQ detected
    0
    0%
    0
    0%
    1
    3.3%
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    Day 5 < LLOQ detected
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    1
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    Day 6 < LLOQ TND
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    Day 7 < LLOQ detected
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    1
    NaN
    0
    NaN
    Day 8 < LLOQ detected
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    1
    NaN
    0
    NaN
    Day 10 < LLOQ TND
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    1
    NaN
    0
    NaN
    Week 48 < LLOQ TND
    0
    0%
    0
    0%
    1
    3.3%
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN

    Adverse Events

    Time Frame Adverse Events: First dose date up to Day 3 plus 30 days; All-Cause Mortality: First dose date up to Week 48
    Adverse Event Reporting Description The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug (voxilaprevir or placebo). Data were summarized by dose.
    Arm/Group Title Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg
    Arm/Group Description Participants with HCV infection received placebo once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, and 3. Participants with HCV infection received voxilaprevir 50 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 300 mg once daily for 3 days under fasted conditions. This arm was part of cohorts 1 and 2. Participants with HCV infection received voxilaprevir 100 mg once daily for 3 days under fed conditions. This arm was part of cohorts 1, 2, 3, 4, 5 and 6. Participants with HCV infection received voxilaprevir 100 mg on Day 1 and voxilaprevir 100 mg plus SOF/VEL (400/100 mg) FDC on Days 2 and 3 after moderate fat meal. This arm was part of cohort 10.
    All Cause Mortality
    Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/14 (0%) 0/30 (0%) 0/15 (0%) 0/6 (0%) 0/16 (0%)
    Serious Adverse Events
    Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/14 (0%) 0/30 (0%) 0/15 (0%) 1/6 (16.7%) 0/16 (0%)
    Cardiac disorders
    Atrial fibrillation 0/8 (0%) 0/14 (0%) 0/30 (0%) 0/15 (0%) 1/6 (16.7%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Voxilaprevir 50 mg Voxilaprevir 100 mg Voxilaprevir 300 mg Voxilaprevir 100 mg Fed Voxilaprevir 100 mg + SOF/VEL 400/100 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/8 (25%) 2/14 (14.3%) 2/30 (6.7%) 2/15 (13.3%) 1/6 (16.7%) 2/16 (12.5%)
    Gastrointestinal disorders
    Constipation 1/8 (12.5%) 0/14 (0%) 0/30 (0%) 0/15 (0%) 0/6 (0%) 0/16 (0%)
    Diarrhoea 1/8 (12.5%) 0/14 (0%) 2/30 (6.7%) 1/15 (6.7%) 0/6 (0%) 1/16 (6.3%)
    Injury, poisoning and procedural complications
    Contusion 0/8 (0%) 1/14 (7.1%) 0/30 (0%) 0/15 (0%) 0/6 (0%) 0/16 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/8 (0%) 1/14 (7.1%) 0/30 (0%) 0/15 (0%) 0/6 (0%) 0/16 (0%)
    Pain in extremity 0/8 (0%) 1/14 (7.1%) 0/30 (0%) 0/15 (0%) 0/6 (0%) 0/16 (0%)
    Nervous system disorders
    Dizziness 0/8 (0%) 0/14 (0%) 0/30 (0%) 0/15 (0%) 1/6 (16.7%) 0/16 (0%)
    Headache 2/8 (25%) 0/14 (0%) 1/30 (3.3%) 0/15 (0%) 1/6 (16.7%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Dermatitis contact 0/8 (0%) 0/14 (0%) 0/30 (0%) 1/15 (6.7%) 0/6 (0%) 0/16 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02185794
    Other Study ID Numbers:
    • GS-US-338-1121
    First Posted:
    Jul 10, 2014
    Last Update Posted:
    Sep 17, 2020
    Last Verified:
    Aug 1, 2020