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    Clinical Trial Results:
    A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Coadministration of ABT-450 with Ritonavir (ABT-450/r) and ABT-267 in Adults with Chronic Hepatitis C Virus Infection (PEARL-I)

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    2011-005762-38
    Trial protocol
    ES   HU   IT  
    Global end of trial date
    17 Feb 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    18 May 2016
    First version publication date
    18 May 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    M13-393
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01685203
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co. KG
    Sponsor organisation address
    Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire , United Kingdom, SL6 4XE
    Public contact
    Global Medical Information, AbbVie, +001 800-633-9110,
    Scientific contact
    Nilou Mobashery, MD, AbbVie, nilou.mobashery@abbvie.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Feb 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the safety and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.
    Protection of trial subjects
    Participants read and understood information provided about the study and gave written permission.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    14 Aug 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 19
    Country: Number of subjects enrolled
    Spain: 60
    Country: Number of subjects enrolled
    France: 74
    Country: Number of subjects enrolled
    Hungary: 18
    Country: Number of subjects enrolled
    Italy: 24
    Country: Number of subjects enrolled
    Romania: 49
    Country: Number of subjects enrolled
    Turkey: 9
    Country: Number of subjects enrolled
    United States: 63
    Worldwide total number of subjects
    316
    EEA total number of subjects
    244
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    291
    From 65 to 84 years
    25
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Group 5 (Genotype 4 (GT4) treatment-experienced, ABT-450 150 mg + ritonavir 100 mg + ABT-267 25 mg (2-DAA) regimen for 12 weeks) was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher SVR rates among subjects receiving the 2-DAA regimen with ribavirin.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Group 1
    Arm description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450/ritonavir
    Investigational medicinal product code
    Other name
    ABT-450 also known as paritaprevir
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet; ABT-450; Capsule; ritonavir ABT-450 150 mg/ritonavir 100 mg once daily for 12 weeks

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    ABT-267 also known as ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg once daily for 12 weeks

    Arm title
    Group 2
    Arm description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450/ritonavir
    Investigational medicinal product code
    Other name
    ABT-450 also known as paritaprevir
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet; ABT-450; Capsule; ritonavir ABT-450 150 mg/ritonavir 100 mg once daily for 12 weeks

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    ABT-267 also known as ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg once daily for 12 weeks

    Arm title
    Group 3
    Arm description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450/ritonavir
    Investigational medicinal product code
    Other name
    ABT-450 also known as paritaprevir
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet; ABT-450; Capsule; ritonavir ABT-450 150 mg/ritonavir 100 mg once daily for 12 weeks

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    ABT-267 also known as ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg once daily for 12 weeks

    Arm title
    Group 4
    Arm description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4 -infected participants
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450/ritonavir
    Investigational medicinal product code
    Other name
    ABT-450 also known as paritaprevir
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet; ABT-450; Capsule; ritonavir ABT-450 150 mg/ritonavir 100 mg once daily for 12 weeks

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    ABT-267 also known as ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg once daily for 12 weeks

    Investigational medicinal product name
    Ribavirin (RBV)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1,000 mg/day if body weight < 75 kg or 1,200 mg/day if body weight ≥ 75 kg, divided twice daily, for 12 weeks

    Arm title
    Group 6
    Arm description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450/ritonavir
    Investigational medicinal product code
    Other name
    ABT-450 also known as paritaprevir
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet; ABT-450; Capsule; ritonavir ABT-450 150 mg/ritonavir 100 mg once daily for 12 weeks

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    ABT-267 also known as ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg once daily for 12 weeks

    Investigational medicinal product name
    Ribavirin (RBV)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1,000 mg/day if body weight < 75 kg or 1,200 mg/day if body weight ≥ 75 kg, divided twice daily, for 12 weeks

    Arm title
    Group 7
    Arm description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450/ritonavir
    Investigational medicinal product code
    Other name
    ABT-450 also known as paritaprevir
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet; ABT-450; Capsule; ritonavir ABT-450 150 mg/ritonavir 100 mg once daily for 24 weeks

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    ABT-267 also known as ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg once daily for 24 weeks

    Arm title
    Group 8
    Arm description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450/ritonavir
    Investigational medicinal product code
    Other name
    ABT-450 also known as paritaprevir
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet; ABT-450; Capsule; ritonavir ABT-450 150 mg/ritonavir 100 mg once daily for 24 weeks

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    ABT-267 also known as ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg once daily for 24 weeks

    Number of subjects in period 1
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Started
    44
    42
    40
    42
    49
    47
    52
    Completed study drug
    42
    40
    39 [1]
    42
    49
    43 [2]
    52
    Completed
    40
    39
    40
    41
    49
    44
    52
    Not completed
    4
    3
    0
    1
    0
    3
    0
         Adverse event, non-fatal
             -
             -
             -
             -
             -
             2
             -
         Adverse event and withdrew consent
             1
             -
             -
             -
             -
             -
             -
         Patient's decision
             -
             -
             -
             -
             -
             1
             -
         Lost to follow-up
             3
             3
             -
             1
             -
             -
             -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One subject discontinued study drug but continued the study in the post-treatment period.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One subject discontinued study drug but continued the study in the post-treatment period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 1
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants

    Reporting group title
    Group 2
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants

    Reporting group title
    Group 3
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants

    Reporting group title
    Group 4
    Reporting group description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4 -infected participants

    Reporting group title
    Group 6
    Reporting group description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants

    Reporting group title
    Group 7
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis

    Reporting group title
    Group 8
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis

    Reporting group values
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8 Total
    Number of subjects
    44 42 40 42 49 47 52 316
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0 0 0
        Adults (18-64 years)
    42 42 36 41 48 40 42 291
        From 65-84 years
    2 0 4 1 1 7 10 25
        85 years and over
    0 0 0 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    48.9 ± 10.03 55.8 ± 6.88 54.2 ± 9.61 44.2 ± 12.67 50.9 ± 10.13 57.8 ± 7.12 57.1 ± 6.02 -
    Gender categorical
    Units: Subjects
        Female
    20 17 25 14 13 24 19 132
        Male
    24 25 15 28 36 23 33 184
    Subject analysis sets

    Subject analysis set title
    Overall study
    Subject analysis set type
    Full analysis
    Subject analysis set description
    All participants who received at least 1 dose of study drug.

    Subject analysis sets values
    Overall study
    Number of subjects
    316
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    291
        From 65-84 years
    25
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    52.8 ± 10.1
    Gender categorical
    Units: Subjects
        Female
    132
        Male
    184

    End points

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    End points reporting groups
    Reporting group title
    Group 1
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants

    Reporting group title
    Group 2
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants

    Reporting group title
    Group 3
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants

    Reporting group title
    Group 4
    Reporting group description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4 -infected participants

    Reporting group title
    Group 6
    Reporting group description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants

    Reporting group title
    Group 7
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis

    Reporting group title
    Group 8
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis

    Subject analysis set title
    Overall study
    Subject analysis set type
    Full analysis
    Subject analysis set description
    All participants who received at least 1 dose of study drug.

    Primary: Percentage of participants in each treatment group with sustained virologic response 12 weeks post-treatment

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    End point title
    Percentage of participants in each treatment group with sustained virologic response 12 weeks post-treatment
    End point description
    The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [<LLOQ]) 12 weeks after the last dose of study drug.
    End point type
    Primary
    End point timeframe
    12 weeks after the last actual dose of study drug
    End point values
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Number of subjects analysed
    44 [1]
    42 [2]
    40 [3]
    42 [4]
    49 [5]
    47 [6]
    52 [7]
    Units: Percentage of participants
        number (confidence interval 95%)
    90.9 (78.3 to 97.5)
    95.2 (83.8 to 99.4)
    90 (76.3 to 97.2)
    100 (91.6 to 100)
    100 (92.7 to 100)
    97.9 (88.7 to 99.9)
    98.1 (89.7 to 100)
    Notes
    [1] - All randomized participants who received at least 1 dose of study drug.
    [2] - All participants who received at least 1 dose of study drug.
    [3] - All participants who received at least 1 dose of study drug.
    [4] - All randomized participants who received at least 1 dose of study drug.
    [5] - All participants who received at least 1 dose of study drug.
    [6] - All participants who received at least 1 dose of study drug.
    [7] - All participants who received at least 1 dose of study drug.
    Statistical analysis title
    Pairwise comparison between Groups 2 and 3
    Comparison groups
    Group 2 v Group 3
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.381 [8]
    Method
    Regression, Logistic
    Confidence interval
    Notes
    [8] - Treatment group, baseline log(subscript)10(subscript) HCV RNA level and Interleukin-28B (IL28B) genotype (CC or non-CC) were used as predictors
    Statistical analysis title
    Additional comparison, Group 1 vs Group 4
    Comparison groups
    Group 1 v Group 4
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.086 [9]
    Method
    Stratum-adjusted Mantel-Haenszel
    Confidence interval
    Notes
    [9] - Difference in rates after adjusting for Interleukin-28 (IL28) genotype (CC or Non-CC) using stratum-adjusted Mantel-Haenszel proportions and continuity-corrected variances.

    Secondary: Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment

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    End point title
    Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment
    End point description
    The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [<LLOQ]) 24 weeks after the last dose of study drug.
    End point type
    Secondary
    End point timeframe
    24 weeks after the last actual dose of study drug
    End point values
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Number of subjects analysed
    44 [10]
    42 [11]
    40 [12]
    42 [13]
    49 [14]
    47 [15]
    52 [16]
    Units: Percentage of participants
        number (confidence interval 95%)
    86.4 (72.6 to 94.8)
    92.9 (80.5 to 98.5)
    90 (76.3 to 97.2)
    100 (91.6 to 100)
    100 (92.7 to 100)
    97.9 (88.7 to 99.9)
    98.1 (89.7 to 100)
    Notes
    [10] - All randomized participants who received at least 1 dose of study drug.
    [11] - All participants who received at least 1 dose of study drug.
    [12] - All participants who received at least 1 dose of study drug.
    [13] - All randomized participants who received at least 1 dose of study drug.
    [14] - All participants who received at least 1 dose of study drug.
    [15] - All participants who received at least 1 dose of study drug.
    [16] - All participants who received at least 1 dose of study drug.
    No statistical analyses for this end point

    Secondary: Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure

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    End point title
    Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure
    End point description
    Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment), or failure to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8
    End point values
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Number of subjects analysed
    44 [17]
    42 [18]
    40 [19]
    42 [20]
    49 [21]
    47 [22]
    52 [23]
    Units: Percentage of participants
        number (confidence interval 95%)
    2.3 (0.1 to 12)
    0 (0 to 8.4)
    2.5 (0.1 to 13.2)
    0 (0 to 8.4)
    0 (0 to 7.3)
    0 (0 to 7.5)
    0 (0 to 6.8)
    Notes
    [17] - All randomized participants who received at least 1 dose of study drug.
    [18] - All participants who received at least 1 dose of study drug.
    [19] - All participants who received at least 1 dose of study drug.
    [20] - All randomized participants who received at least 1 dose of study drug.
    [21] - All participants who received at least 1 dose of study drug.
    [22] - All participants who received at least 1 dose of study drug.
    [23] - All participants who received at least 1 dose of study drug.
    No statistical analyses for this end point

    Secondary: Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.

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    End point title
    Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.
    End point description
    Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment.
    End point type
    Secondary
    End point timeframe
    Within 12 weeks after the last dose of study drug
    End point values
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Number of subjects analysed
    42 [24]
    40 [25]
    39 [26]
    42 [27]
    49 [28]
    44 [29]
    52 [30]
    Units: Percentage of participants
        number (confidence interval 95%)
    4.8 (0.6 to 16.2)
    0 (0 to 8.8)
    7.7 (1.6 to 20.9)
    0 (0 to 8.4)
    0 (0 to 7.3)
    0 (0 to 8)
    1.9 (0 to 10.3)
    Notes
    [24] - Subjects who rcvd at least 1 dose of study drug and ended Tx with HCV RNA <LLOQ at the last Tx visit
    [25] - Subjects who rcvd at least 1 dose of study drug and ended Tx with HCV RNA <LLOQ at the last Tx visit
    [26] - Subjects who rcvd at least 1 dose of study drug and ended Tx with HCV RNA <LLOQ at the last Tx visit
    [27] - Subjects who rcvd at least 1 dose of study drug and ended Tx with HCV RNA <LLOQ at the last Tx visit
    [28] - Subjects who rcvd at least 1 dose of study drug and ended Tx with HCV RNA <LLOQ at the last Tx visit
    [29] - Subjects who rcvd at least 1 dose of study drug and ended Tx with HCV RNA <LLOQ at the last Tx visit
    [30] - Subjects who rcvd at least 1 dose of study drug and ended Tx with HCV RNA <LLOQ at the last Tx visit
    No statistical analyses for this end point

    Secondary: Percentage of participants in each treatment group with treatment-emergent adverse events

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    End point title
    Percentage of participants in each treatment group with treatment-emergent adverse events
    End point description
    Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug.
    End point type
    Secondary
    End point timeframe
    From the time of study drug administration until 30 days after the last dose, up to 16 weeks for Groups 1, 2, 3, 4, and 6, and up to 28 weeks for Groups 7 and 8
    End point values
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Number of subjects analysed
    44 [31]
    42 [32]
    40 [33]
    42 [34]
    49 [35]
    47 [36]
    52 [37]
    Units: Percentage of participants
        number (not applicable)
    77.3
    73.8
    80
    88.1
    85.7
    85.1
    71.2
    Notes
    [31] - All randomized participants who received at least one dose of study drug.
    [32] - All participants who received at least one dose of study drug.
    [33] - All participants who received at least one dose of study drug.
    [34] - All randomized participants who received at least one dose of study drug.
    [35] - All participants who received at least one dose of study drug.
    [36] - All participants who received at least one dose of study drug.
    [37] - All participants who received at least one dose of study drug.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from study drug administration until 30 days after the last dose, up to 16 wks for Groups 1-4, & 6, and up to 28 wks for Groups 7 & 8. Serious AEs were collected from informed consent until the end of the study, up to 65 wks
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Group 1
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants

    Reporting group title
    Group 2
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants

    Reporting group title
    Group 3
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants

    Reporting group title
    Group 4
    Reporting group description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4 -infected participants

    Reporting group title
    Group 6
    Reporting group description
    ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants

    Reporting group title
    Group 7
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis

    Reporting group title
    Group 8
    Reporting group description
    ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis

    Serious adverse events
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 42 (2.38%)
    1 / 40 (2.50%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    3 / 47 (6.38%)
    2 / 52 (3.85%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    2
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    1 / 52 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    1 / 52 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    1 / 47 (2.13%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    1 / 47 (2.13%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatic neoplasm
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    1 / 47 (2.13%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Partial seizures
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    1 / 52 (1.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Device extrusion
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 40 (2.50%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    1 / 47 (2.13%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Group 1 Group 2 Group 3 Group 4 Group 6 Group 7 Group 8
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 44 (68.18%)
    24 / 42 (57.14%)
    26 / 40 (65.00%)
    32 / 42 (76.19%)
    38 / 49 (77.55%)
    34 / 47 (72.34%)
    33 / 52 (63.46%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 40 (2.50%)
    1 / 42 (2.38%)
    1 / 49 (2.04%)
    7 / 47 (14.89%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    1
    2
    7
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    11 / 44 (25.00%)
    3 / 42 (7.14%)
    2 / 40 (5.00%)
    10 / 42 (23.81%)
    16 / 49 (32.65%)
    10 / 47 (21.28%)
    7 / 52 (13.46%)
         occurrences all number
    12
    6
    2
    14
    21
    12
    9
    Fatigue
         subjects affected / exposed
    3 / 44 (6.82%)
    6 / 42 (14.29%)
    0 / 40 (0.00%)
    5 / 42 (11.90%)
    9 / 49 (18.37%)
    4 / 47 (8.51%)
    6 / 52 (11.54%)
         occurrences all number
    4
    6
    0
    7
    11
    4
    6
    Influenza like illness
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    2 / 40 (5.00%)
    0 / 42 (0.00%)
    1 / 49 (2.04%)
    0 / 47 (0.00%)
    2 / 52 (3.85%)
         occurrences all number
    0
    1
    2
    0
    1
    0
    2
    Irritability
         subjects affected / exposed
    3 / 44 (6.82%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    6 / 42 (14.29%)
    2 / 49 (4.08%)
    1 / 47 (2.13%)
    0 / 52 (0.00%)
         occurrences all number
    3
    0
    0
    6
    2
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 42 (7.14%)
    0 / 40 (0.00%)
    1 / 42 (2.38%)
    2 / 49 (4.08%)
    2 / 47 (4.26%)
    2 / 52 (3.85%)
         occurrences all number
    1
    3
    0
    1
    2
    2
    3
    Pyrexia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    1 / 42 (2.38%)
    3 / 49 (6.12%)
    1 / 47 (2.13%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    1
    3
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    4 / 42 (9.52%)
    2 / 49 (4.08%)
    1 / 47 (2.13%)
    2 / 52 (3.85%)
         occurrences all number
    2
    0
    0
    4
    2
    1
    2
    Insomnia
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    4 / 42 (9.52%)
    8 / 49 (16.33%)
    3 / 47 (6.38%)
    4 / 52 (7.69%)
         occurrences all number
    2
    1
    0
    4
    8
    4
    4
    Depression
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    1 / 42 (2.38%)
    3 / 49 (6.12%)
    1 / 47 (2.13%)
    1 / 52 (1.92%)
         occurrences all number
    1
    0
    0
    1
    3
    1
    1
    Investigations
    Blood pressure increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    2 / 40 (5.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    1 / 42 (2.38%)
    0 / 49 (0.00%)
    3 / 47 (6.38%)
    0 / 52 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 42 (4.76%)
    2 / 40 (5.00%)
    2 / 42 (4.76%)
    4 / 49 (8.16%)
    3 / 47 (6.38%)
    5 / 52 (9.62%)
         occurrences all number
    0
    2
    2
    2
    4
    3
    6
    Dyspnoea exertional
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    2 / 42 (4.76%)
    3 / 49 (6.12%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    0
    0
    0
    2
    5
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    2 / 40 (5.00%)
    0 / 42 (0.00%)
    1 / 49 (2.04%)
    0 / 47 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    1
    0
    2
    0
    1
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    2 / 47 (4.26%)
    3 / 52 (5.77%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    3 / 40 (7.50%)
    0 / 42 (0.00%)
    3 / 49 (6.12%)
    0 / 47 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    1
    1
    3
    0
    3
    0
    1
    Headache
         subjects affected / exposed
    13 / 44 (29.55%)
    14 / 42 (33.33%)
    10 / 40 (25.00%)
    14 / 42 (33.33%)
    14 / 49 (28.57%)
    9 / 47 (19.15%)
    10 / 52 (19.23%)
         occurrences all number
    16
    16
    11
    18
    16
    11
    11
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 42 (7.14%)
    1 / 40 (2.50%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    2 / 47 (4.26%)
    0 / 52 (0.00%)
         occurrences all number
    1
    4
    1
    0
    0
    2
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    2 / 42 (4.76%)
    1 / 49 (2.04%)
    3 / 47 (6.38%)
    1 / 52 (1.92%)
         occurrences all number
    0
    1
    0
    2
    1
    3
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    1 / 42 (2.38%)
    1 / 49 (2.04%)
    1 / 47 (2.13%)
    4 / 52 (7.69%)
         occurrences all number
    1
    1
    0
    2
    1
    1
    4
    Diarrhoea
         subjects affected / exposed
    2 / 44 (4.55%)
    6 / 42 (14.29%)
    0 / 40 (0.00%)
    6 / 42 (14.29%)
    3 / 49 (6.12%)
    7 / 47 (14.89%)
    7 / 52 (13.46%)
         occurrences all number
    2
    6
    0
    7
    4
    8
    8
    Dyspepsia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    2 / 42 (4.76%)
    4 / 49 (8.16%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    2
    4
    0
    0
    Flatulence
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    1 / 47 (2.13%)
    3 / 52 (5.77%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    3
    Nausea
         subjects affected / exposed
    4 / 44 (9.09%)
    8 / 42 (19.05%)
    0 / 40 (0.00%)
    7 / 42 (16.67%)
    6 / 49 (12.24%)
    5 / 47 (10.64%)
    5 / 52 (9.62%)
         occurrences all number
    4
    9
    0
    9
    7
    5
    6
    Vomiting
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 42 (7.14%)
    0 / 40 (0.00%)
    2 / 42 (4.76%)
    0 / 49 (0.00%)
    2 / 47 (4.26%)
    1 / 52 (1.92%)
         occurrences all number
    0
    4
    0
    6
    0
    2
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 44 (0.00%)
    7 / 42 (16.67%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    3 / 49 (6.12%)
    1 / 47 (2.13%)
    0 / 52 (0.00%)
         occurrences all number
    0
    7
    0
    0
    5
    1
    0
    Pruritus
         subjects affected / exposed
    2 / 44 (4.55%)
    6 / 42 (14.29%)
    0 / 40 (0.00%)
    1 / 42 (2.38%)
    5 / 49 (10.20%)
    8 / 47 (17.02%)
    9 / 52 (17.31%)
         occurrences all number
    2
    8
    0
    1
    7
    10
    9
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    2 / 42 (4.76%)
    1 / 49 (2.04%)
    4 / 47 (8.51%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    2
    1
    4
    0
    Back pain
         subjects affected / exposed
    3 / 44 (6.82%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    2 / 42 (4.76%)
    4 / 49 (8.16%)
    6 / 47 (12.77%)
    5 / 52 (9.62%)
         occurrences all number
    3
    0
    0
    2
    4
    6
    5
    Myalgia
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 42 (4.76%)
    2 / 40 (5.00%)
    0 / 42 (0.00%)
    5 / 49 (10.20%)
    3 / 47 (6.38%)
    2 / 52 (3.85%)
         occurrences all number
    0
    2
    2
    0
    5
    4
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    1 / 42 (2.38%)
    3 / 49 (6.12%)
    2 / 47 (4.26%)
    1 / 52 (1.92%)
         occurrences all number
    1
    1
    0
    1
    3
    2
    1
    Hyperglycaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    2 / 40 (5.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Increased appetite
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    3 / 47 (6.38%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    3
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 40 (2.50%)
    1 / 42 (2.38%)
    2 / 49 (4.08%)
    3 / 47 (6.38%)
    1 / 52 (1.92%)
         occurrences all number
    1
    0
    1
    1
    2
    5
    1
    Influenza
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    2 / 40 (5.00%)
    0 / 42 (0.00%)
    2 / 49 (4.08%)
    1 / 47 (2.13%)
    2 / 52 (3.85%)
         occurrences all number
    1
    1
    2
    0
    2
    1
    4
    Nasopharyngitis
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 42 (2.38%)
    2 / 40 (5.00%)
    2 / 42 (4.76%)
    6 / 49 (12.24%)
    4 / 47 (8.51%)
    4 / 52 (7.69%)
         occurrences all number
    2
    1
    3
    2
    6
    4
    4
    Rhinitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    0 / 42 (0.00%)
    3 / 49 (6.12%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 40 (0.00%)
    2 / 42 (4.76%)
    1 / 49 (2.04%)
    2 / 47 (4.26%)
    4 / 52 (7.69%)
         occurrences all number
    1
    0
    0
    2
    1
    2
    4
    Urinary tract infection
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 42 (4.76%)
    2 / 40 (5.00%)
    1 / 42 (2.38%)
    2 / 49 (4.08%)
    2 / 47 (4.26%)
    1 / 52 (1.92%)
         occurrences all number
    3
    2
    2
    1
    3
    3
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    2 / 40 (5.00%)
    0 / 42 (0.00%)
    0 / 49 (0.00%)
    0 / 47 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jun 2012
    Protocol Amendment No. 1 was dated 27 June 2012, and 86 subjects were enrolled into the study under this amendment. The purpose of Amendment No. 1 is summarized as follows: ● Modify the study design, by removing the HCV GT1a 8-week treatment group. ● Revise the study objectives based on the modified study design. ● Revise the efficacy variables based on the modified study design. ● Revise the efficacy endpoints based on the modified study design. ● Revise how study enrollment would occur. ● Update the data required for review prior to opening Group 1 and/or Group 4. ● Clarify post study treatment information. ● Clarify the efficacy stopping criteria. ● Include the collection of optional mRNA study samples. ● Incorporate Administrative Change 1. ● Address any inconsistencies throughout the protocol.
    21 Jan 2013
    Protocol Amendment No. 2 was dated 21 January 2013, and 127 subjects were enrolled into the study under this amendment. The purpose of Amendment No. 2 is summarized as follows: ● Modify the study design by: ○ Removing the HCV GT1a 12-week treatment group. ○ Removing the HCV GT1b 8-week treatment group. ○ Adding 2 GT4 treatment-naïve treatment arms (Groups 1 and 4). ○ Adding 2 GT4 treatment-experienced treatment arms (Groups 5 and 6). ○ Adding GT1b treatment-naïve and treatment-experienced subjects with compensated cirrhosis (Groups 7 and 8). ● Revise the study objectives based on the modified study design. ● Revise the efficacy variables based on the modified study design. ● Revise the statistical analyses based on the modified study design. ● Revise how study enrollment will occur. ● Add the data required for review prior to opening Groups 5 – 8. ● Clarify the efficacy stopping criteria. ● Change the primary Study Designated Physician. ● Incorporate Administrative Change 2. ● Update Section 1.0 – Title Page. ● Update Section 1.2 – Synopsis, Section 1.3 – List of Abbreviations and Definition of Terms, and Section 2.0 – Table of Contents. ● Update Section 3.0 – Introduction, Section 4.0 – Study Objectives, Section 5.0 – Investigational Plan, and Section 6.0 – Adverse Events and all subsections under each of these sections. ● Update Section 8.0 – Statistical Methods and Determination of Sample Size and all subsections under this section. ● Update Section 15.0 – Reference List. ● Added Appendix C – Clinical Toxicity Grades. ● Address any inconsistencies throughout the protocol.
    08 Apr 2013
    Protocol Amendment No. 3 was dated 08 April 2013, and 95 subjects were enrolled into the study under this amendment. The purpose of Amendment No. 3 is summarized as follows: ● Prohibit the use of hormonal contraceptives during study drug administration.
    13 Aug 2013
    Protocol Amendment No. 4 was dated 13 August 2013, and 6 subjects were enrolled into the study under this amendment. The purpose of Amendment No. 4 is summarized as follows: ● Address inconsistencies throughout the protocol. ● Modify Inclusion Criterion No. 2 and corresponding contraception language throughout the protocol to specify contraindication of hormone eluting IUDs. ● Modify Inclusion Criterion No. 11 to include FibroTest/APRI. ● Modify Exclusion Criterion No. 8 to allow for rescreening of subjects who test positive for alcohol on their initial drug/alcohol screening. ● Modify Exclusion Criterion No. 20 to exclude an Absolute Neutrophil Count (ANC) < 1200 cells/μL for subjects of African descent who are black. ● Modify Section 5.1.1.1 Rescreening language. ● Remove language prohibiting the use of inhibitors of CYP2C8 from Section 5.2.3.3 Prohibited Therapy. ● Add a laboratory collection at Post-Treatment Week 12 visit in Table 2 for subjects participating in Substudy 2. ● Remove requirement that sites maintain a MEMS cap accountability form provided by AbbVie. ● Modify Section 5.3.2.3 Disposition of Samples to remove "An inventory of the samples included will accompany the package." ● Modify Section 5.5.7 Drug Accountability language. ● Modify Section 6.7.3 to include additional language regarding the management of bilirubin elevations. ● Modify definition of on-treatment virologic failure. ● Add footnotes for Ascites to Table 4. ● Modify Section 8.1.3.2 Secondary Efficacy Endpoints.
    17 Oct 2013
    Amendment No. 5 was dated 17 October 2013, and 2 subjects were enrolled under this amendment. The purpose of Amendment No. 5 is summarized as follows: ● Modify the text to reflect the decision to extend the treatment period for Groups 7 and 8 subjects to 24 weeks. ● Modify study design to reflect the decision to open enrollment for Group 6 (the HCV GT4 treatment-experienced group to be treated with the 2-DAA regimen plus RBV) but not Group 5 (the HCV GT4 treatment-experienced group to be treated with the 2-DAA regimen without RBV). ● Remove the interim analyses for all subjects who have completed treatment.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Not applicable

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/25837829
    http://www.ncbi.nlm.nih.gov/pubmed/26170136
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