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    Clinical Trial Results:
    A Randomized, Open-Label, Multicenter Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics, of ABT-450 with Ritonavir (ABT-450/r) in Combination with ABT-267 and/or ABT-333 With and Without Ribavirin (RBV) for 8, 12 or 24 Weeks in Treatment-Naïve and Null Responder Subjects with Genotype 1 Chronic Hepatitis C Virus Infection

    Summary
    EudraCT number
    2010-022455-31
    Trial protocol
    GB   ES  
    Global end of trial date
    19 Sep 2013

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Apr 2016
    First version publication date
    13 Jun 2015
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    M11-652
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01464827
    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, 011 800-633-9110,
    Scientific contact
    Daniel Cohen, MD, AbbVie , daniel.cohen@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
    19 Sep 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Sep 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Assess the safety of all treatment regimens and the percentage of subjects achieving 24-week sustained virologic response (SVR24; hepatitis C virus [HCV] ribonucleic acid [RNA] less than the lower limit of quantitation [LLOQ] at post-treatment Week 24) following treatment for 8 weeks versus 12 weeks with 3 direct-acting antiviral agents (DAA) and ribavirin (RBV) in HCV genotype 1-infected treatment-naïve adults.
    Protection of trial subjects
    The study was conducted in accordance with the protocol, ICH guidelines, applicable regulations and guidelines governing clinical study conduct, and the ethical principles that have their origin in the Declaration of Helsinki. All subjects entering the study had to sign an informed consent that was explained to them and questions encouraged.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 Oct 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 36
    Country: Number of subjects enrolled
    United Kingdom: 33
    Country: Number of subjects enrolled
    France: 58
    Country: Number of subjects enrolled
    Germany: 39
    Country: Number of subjects enrolled
    Australia: 8
    Country: Number of subjects enrolled
    New Zealand: 1
    Country: Number of subjects enrolled
    United States: 400
    Country: Number of subjects enrolled
    Canada: 5
    Worldwide total number of subjects
    580
    EEA total number of subjects
    166
    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)
    548
    From 65 to 84 years
    32
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Subjects underwent screening procedures within 35 days prior to enrollment. HCV genotype 1-infected adult male and female subjects who were either treatment-naïve or previous null responders to pegylated interferon (pegIFN) and RBV were eligible to participate.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Group A
    Arm description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 8 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Arm title
    Group B
    Arm description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group C
    Arm description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group D
    Arm description
    Treatment-naïve participants received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Arm title
    Group E
    Arm description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Arm title
    Group F
    Arm description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group G
    Arm description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group H
    Arm description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group I
    Arm description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group J
    Arm description
    Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group K
    Arm description
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group L
    Arm description
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group M
    Arm description
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Arm title
    Group N
    Arm description
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    ABT-450
    Investigational medicinal product code
    Other name
    Paritaprevir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg tablets

    Investigational medicinal product name
    ABT-333
    Investigational medicinal product code
    Other name
    Dasabuvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Other use
    Dosage and administration details
    400 mg tablets

    Investigational medicinal product name
    ABT-267
    Investigational medicinal product code
    Other name
    Ombitasvir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg tablets

    Investigational medicinal product name
    Ritonavir
    Investigational medicinal product code
    Other name
    Norvir
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsules

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

    Number of subjects in period 1
    Group A Group B Group C Group D Group E Group F Group G Group H Group I Group J Group K Group L Group M Group N
    Started
    80
    43
    39
    40
    80
    39
    41
    40
    40
    47
    23
    23
    23
    22
    Treated
    80
    41
    39
    40
    79
    39
    40
    40
    40
    45
    23
    22
    23
    20
    Completed
    77
    36
    39
    36
    72
    38
    37
    37
    37
    44
    21
    21
    21
    19
    Not completed
    3
    7
    0
    4
    8
    1
    4
    3
    3
    3
    2
    2
    2
    3
         Other
    2
    3
    -
    2
    3
    -
    1
    -
    3
    1
    2
    -
    1
    -
         Adverse event, non-fatal
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
         Consent withdrawn by subject
    1
    -
    -
    -
    1
    -
    -
    1
    -
    -
    -
    -
    -
    -
         Not treated
    -
    2
    -
    -
    1
    -
    1
    -
    -
    2
    -
    1
    -
    2
         Lost to follow-up
    -
    2
    -
    2
    3
    1
    2
    2
    -
    -
    -
    1
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group A
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 8 weeks.

    Reporting group title
    Group B
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group C
    Reporting group description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group D
    Reporting group description
    Treatment-naïve participants received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group E
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks.

    Reporting group title
    Group F
    Reporting group description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group G
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group H
    Reporting group description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group title
    Group I
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group title
    Group J
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group K
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group L
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group M
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group title
    Group N
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group values
    Group A Group B Group C Group D Group E Group F Group G Group H Group I Group J Group K Group L Group M Group N Total
    Number of subjects
    80 43 39 40 80 39 41 40 40 47 23 23 23 22 580
    Age categorical
    Units: Subjects
    Age continuous
    Data are provided for the safety population (participants who received at least 1 dose of direct-acting antiviral agent).
    Units: years
        arithmetic mean (standard deviation)
    50.1 ± 9.99 50.8 ± 9.84 51.1 ± 8.07 49 ± 10.59 48.3 ± 10.53 49.4 ± 9.72 51 ± 11.08 51.5 ± 11.95 51.5 ± 9.78 50.6 ± 11.19 48.5 ± 12.91 51.2 ± 12.07 51.5 ± 9.06 54.6 ± 11.78 -
    Gender categorical
    Units: Subjects
        Female
    34 24 14 20 34 19 16 22 24 19 7 10 8 9 260
        Male
    46 19 25 20 46 20 25 18 16 28 16 13 15 13 320

    End points

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    End points reporting groups
    Reporting group title
    Group A
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 8 weeks.

    Reporting group title
    Group B
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group C
    Reporting group description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group D
    Reporting group description
    Treatment-naïve participants received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group E
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks.

    Reporting group title
    Group F
    Reporting group description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group G
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group H
    Reporting group description
    Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group title
    Group I
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group title
    Group J
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group K
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group L
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group M
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group title
    Group N
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Subject analysis set title
    Group A
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 8 weeks.

    Subject analysis set title
    Group B
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Subject analysis set title
    Group C + D
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Treatment-naïve participants received ABT-450 (100 mg or 200 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Subject analysis set title
    Group E
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks.

    Subject analysis set title
    Group F + G
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Treatment-naïve participants received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Subject analysis set title
    Group H + I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Treatment-naïve participants received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Subject analysis set title
    Group J
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Subject analysis set title
    Group K + L
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants who were null-responders to previous HCV treatment received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Subject analysis set title
    Group M + N
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants who were null-responders to previous HCV treatment received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Subject analysis set title
    Groups F + G + K + L
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Participants (treatment-naïve and null-responders) received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Subject analysis set title
    Groups H + I + M + N
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Participants (treatment-naïve and null-responders) received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Subject analysis set title
    Groups C + D + J
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Participants (treatment-naïve and null-responders) received ABT-450 (100 mg or 200 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Subject analysis set title
    Groups F + G + H + I
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Treatment-naïve participants received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 or 24 weeks.

    Subject analysis set title
    Groups K + L + M + N
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Participants who were null-responders to previous HCV treatment received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 or 24 weeks.

    Primary: Number of Participants With Adverse Events (AEs)

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    End point title
    Number of Participants With Adverse Events (AEs) [1]
    End point description
    An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs) and to ribavirin, and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening. A serious adverse event was any event that resulted in death, was life-threatening, resulted in or prolonged hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.
    End point type
    Primary
    End point timeframe
    From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 weeks).
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety was assessed by summarizing the incidence of adverse events.
    End point values
    Group A Group B Group C + D Group E Group F + G Group H + I Group J Group K + L Group M + N
    Number of subjects analysed
    80
    41
    79
    79
    79
    80
    45
    45
    45
    Units: participants
        Any adverse event
    67
    36
    71
    68
    71
    77
    42
    39
    37
        Any adverse event at least possibly DAArelated
    58
    29
    53
    51
    57
    68
    35
    30
    28
        Any severe adverse event
    3
    0
    3
    5
    3
    3
    1
    1
    1
        Any serious adverse event
    0
    0
    2
    2
    1
    1
    0
    0
    2
        Any AE leading to discontinuation of study drug
    1
    0
    0
    0
    3
    3
    1
    0
    1
        Any AE leading to interruption of study drug
    0
    1
    2
    1
    0
    1
    0
    0
    0
        Any AE leading to ribavirin dose modification
    2
    2
    4
    0
    9
    10
    3
    1
    3
        Any fatal adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin

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    End point title
    Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin
    End point description
    The percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (SVR24), defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than the lower limit of quantitation (LLOQ), without any confirmed quantifiable (≥ LLOQ) post-treatment value before that time point. HCV RNA levels were measured from plasma by a central laboratory. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoint was the comparison between treatment-naïve participants following 8 weeks of treatment with 3 DAAs and ribavirin and those with 12 weeks of treatment with 3 DAAs and ribavirin (Group A versus Group G). Participants with missing data were counted as non-responders.
    End point type
    Primary
    End point timeframe
    Post Treatment Week 24
    End point values
    Group A Group B Group C Group D Group E Group F Group G Group H Group I Group J Group K Group L Group M Group N
    Number of subjects analysed
    80
    41
    39
    40
    79
    39
    40
    40
    40
    45
    23
    22
    23
    20
    Units: percentage of participants
        number (not applicable)
    87.5
    82.9
    84.6
    92.5
    88.6
    97.4
    95
    92.5
    90
    88.9
    91.3
    95.5
    91.3
    100
    Statistical analysis title
    Primary analysis
    Statistical analysis description
    The primary efficacy endpoint was the comparison of the percentage of treatment-naïve participants with SVR24 after treatment with 3 DAAs (at the 150 mg ABT-450 dose) and ribavirin for 8 weeks (Group A) versus 12 weeks (Group G).
    Comparison groups
    Group G v Group A
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.406 [3]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.09
         upper limit
    2.61
    Notes
    [2] - Pre-specified 2-sided significance level of 0.05.
    [3] - Logistic regression with baseline log10 HCV RNA level, treatment group, Interleukin 28B genotype (CC or non-CC), HCV subgenotype (1a or non-1a), and geographic region (US or non-US) as predictors. No adjustment for multiple comparison.

    Secondary: Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin

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    End point title
    Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin
    End point description
    This endpoint compares the percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs (ABT-450/ritonavir, ABT-267, and ABT-333) and ribavirin in both treatment naïve and null-responder participants for 8 weeks (Group A) versus 12 weeks (Groups F + G + K + L) versus 24 weeks (Groups H + I + M + N). Participants with missing data were counted as non-responders.
    End point type
    Secondary
    End point timeframe
    Post-Treatment Week 24
    End point values
    Group A Groups F + G + K + L Groups H + I + M + N
    Number of subjects analysed
    80
    124
    123
    Units: percentage of participants
        number (not applicable)
    87.5
    95.2
    92.7
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    The percentage of participants with SVR24 after treatment for 8 weeks versus 12 weeks was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), and ABT-450/ritonavir dose and population (treatment-naïve or null-responders) as predictors.
    Comparison groups
    Group A v Groups F + G + K + L
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    = 0.266 [5]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.08
         upper limit
    2.02
    Notes
    [4] - Pre-specified 2-sided significance level of 0.05.
    [5] - No adjustment for multiple comparison.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    The percentage of participants with SVR24 after treatment for 8 weeks versus 24 weeks was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), ABT-450/ritonavir dose and population (treatment-naïve or null-responders) as predictors.
    Comparison groups
    Group A v Groups H + I + M + N
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority [6]
    P-value
    = 0.525 [7]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.18
         upper limit
    2.4
    Notes
    [6] - Pre-specified 2-sided significance level of 0.05.
    [7] - No adjustment for multiple comparison.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    The percentage of participants with SVR24 after treatment for 12 weeks versus 24 weeks was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), ABT-450/ritonavir dose and population (treatment-naïve or null-responders) as predictors.
    Comparison groups
    Groups F + G + K + L v Groups H + I + M + N
    Number of subjects included in analysis
    247
    Analysis specification
    Pre-specified
    Analysis type
    superiority [8]
    P-value
    = 0.375 [9]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    4.92
    Notes
    [8] - Pre-specified 2-sided significance level of 0.05.
    [9] - No adjustment for multiple comparison.

    Secondary: Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin

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    End point title
    Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin
    End point description
    This endpoint compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 2 DAAs (ABT-450/ritonavir plus ABT-333 [Group B] or ABT-450/ritonavir plus ABT-267 [Groups C + D + J]) and ribavirin versus 3 DAAs (ABT-450/ritonavir plus ABT-333 and ABT-267) and ribavirin (Groups F + G + K + L). Participants with missing data were counted as non-responders.
    End point type
    Secondary
    End point timeframe
    Post-Treatment Week 24
    End point values
    Group B Groups F + G + K + L Groups C + D + J
    Number of subjects analysed
    41
    124
    124
    Units: percentage of participants
        number (not applicable)
    82.9
    95.2
    88.7
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    The percentage of participants with SVR24 after treatment with 2 DAAs and ribavirin versus 3 DAAs and ribavirin was compared using stratum-adjusted Mantel-Haenszel (MH) method with Interleukin 28B genotype (CC or non-CC) and HCV subgenotype (1a or non-1a).
    Comparison groups
    Group B v Groups F + G + K + L
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    superiority [10]
    P-value
    = 0.068 [11]
    Method
    Mantel-Haenszel
    Parameter type
    Difference (Group B - Groups F + G + K )
    Point estimate
    -12.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -25.2
         upper limit
    0.88
    Notes
    [10] - Pre-specified 2-sided significance level of 0.05.
    [11] - The Mantel-Haenszel method was used because logistic regression failed due to separation or quasi-separation. There was no adjustment for multiple comparison.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    The percentage of participants with SVR24 after treatment with 2 DAAs and ribavirin versus 3 DAAs and ribavirin was compared using stratum-adjusted Mantel-Haenszel (MH) method with Interleukin 28B genotype (CC or non-CC) and HCV subgenotype (1a or non-1a).
    Comparison groups
    Groups F + G + K + L v Groups C + D + J
    Number of subjects included in analysis
    248
    Analysis specification
    Pre-specified
    Analysis type
    superiority [12]
    P-value
    = 0.065 [13]
    Method
    Mantel-Haenszel
    Parameter type
    Difference (Group C+D+J - Group F+G+K+L)
    Point estimate
    -6.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.93
         upper limit
    0.43
    Notes
    [12] - Pre-specified 2-sided significance level of 0.05.
    [13] - The Mantel-Haenszel method was used because logistic regression failed due to separation or quasi-separation. No adjustment for multiple comparison.

    Secondary: Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin

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    End point title
    Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin
    End point description
    This endpoint compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs with or without ribavirin (Group E versus Groups F + G + K + L). Participants with missing data were counted as non-responders.
    End point type
    Secondary
    End point timeframe
    Post-Treatment Week 24
    End point values
    Group E Groups F + G + K + L
    Number of subjects analysed
    79
    124
    Units: Percentage of participants
        number (not applicable)
    88.6
    95.2
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    The percentage of participants with SVR24 after treatment with 3 DAAs with and without ribavirin was compared using a stratum-adjusted Mantel-Haenszel (MH) method with Interleukin 28B genotype (CC or non-CC) and HCV subgenotype (1a or non-1a).
    Comparison groups
    Group E v Groups F + G + K + L
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority [14]
    P-value
    = 0.106 [15]
    Method
    Mantel-Haenszel
    Parameter type
    Difference (Group E - Group F+G+K+L)
    Point estimate
    -7.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.77
         upper limit
    1.51
    Notes
    [14] - Pre-specified 2-sided significance level of 0.05.
    [15] - The Mantel-Haenszel method was used because logistic regression failed due to separation or quasi-separation. No adjustment for multiple comparison.

    Secondary: Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders

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    End point title
    Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders
    End point description
    This endpoint compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs and ribavirin in participants who were treatment-naïve versus those who were null-responders to previous HCV therapy (Groups F + G + H + I versus Groups K + L + M + N). Participants with missing data were counted as non-responders.
    End point type
    Secondary
    End point timeframe
    Post-Treatment Week 24
    End point values
    Groups F + G + H + I Groups K + L + M + N
    Number of subjects analysed
    159
    88
    Units: percentage of participants
        number (not applicable)
    93.7
    94.3
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    The percentage of participants with SVR24 after treatment with 3 DAAs and ribavirin in treatment-naïve versus null-responders was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), and ABT-450/ritonavir dose as predictors.
    Comparison groups
    Groups F + G + H + I v Groups K + L + M + N
    Number of subjects included in analysis
    247
    Analysis specification
    Pre-specified
    Analysis type
    superiority [16]
    P-value
    = 0.616 [17]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.37
         upper limit
    5.34
    Notes
    [16] - Pre-specified 2-sided significance level of 0.05.
    [17] - No adjustment for multiple comparison.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 28 weeks
    Adverse event reporting additional description
    Treatment groups differing only in ABT-450 dose (100 mg, 150 mg or 200 mg) were combined for safety analyses.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Group A
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 8 weeks.

    Reporting group title
    Group B
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

    Reporting group title
    Group C + D
    Reporting group description
    Treatment-naïve participants received ABT-450 (100 mg or 200 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group E
    Reporting group description
    Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks.

    Reporting group title
    Group F + G
    Reporting group description
    Treatment-naïve participants received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group H + I
    Reporting group description
    Treatment-naïve participants received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Reporting group title
    Group J
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group K + L
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

    Reporting group title
    Group M + N
    Reporting group description
    Participants who were null-responders to previous HCV treatment received ABT-450 (100 mg or 150 mg) and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

    Serious adverse events
    Group A Group B Group C + D Group E Group F + G Group H + I Group J Group K + L Group M + N
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    2 / 79 (2.53%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    1 / 80 (1.25%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 43 (4.65%)
         number of deaths (all causes)
    0
    1
    0
    1
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Lung disorder
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Nervous system disorders
    Cervicobrachial syndrome
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    1 / 80 (1.25%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Group A Group B Group C + D Group E Group F + G Group H + I Group J Group K + L Group M + N
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    64 / 80 (80.00%)
    33 / 41 (80.49%)
    66 / 79 (83.54%)
    59 / 79 (74.68%)
    66 / 79 (83.54%)
    74 / 80 (92.50%)
    40 / 45 (88.89%)
    36 / 45 (80.00%)
    34 / 43 (79.07%)
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    7 / 80 (8.75%)
    1 / 41 (2.44%)
    8 / 79 (10.13%)
    5 / 79 (6.33%)
    3 / 79 (3.80%)
    12 / 80 (15.00%)
    10 / 45 (22.22%)
    4 / 45 (8.89%)
    4 / 43 (9.30%)
         occurrences all number
    7
    1
    8
    7
    4
    17
    11
    4
    4
    Chest pain
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 41 (2.44%)
    2 / 79 (2.53%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    4 / 80 (5.00%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    2
    0
    1
    4
    1
    3
    0
    Chills
         subjects affected / exposed
    4 / 80 (5.00%)
    1 / 41 (2.44%)
    1 / 79 (1.27%)
    1 / 79 (1.27%)
    1 / 79 (1.27%)
    3 / 80 (3.75%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    4
    1
    1
    1
    1
    3
    1
    0
    2
    Fatigue
         subjects affected / exposed
    29 / 80 (36.25%)
    13 / 41 (31.71%)
    22 / 79 (27.85%)
    16 / 79 (20.25%)
    22 / 79 (27.85%)
    30 / 80 (37.50%)
    12 / 45 (26.67%)
    12 / 45 (26.67%)
    9 / 43 (20.93%)
         occurrences all number
    33
    13
    25
    17
    23
    35
    13
    15
    12
    Irritability
         subjects affected / exposed
    1 / 80 (1.25%)
    4 / 41 (9.76%)
    5 / 79 (6.33%)
    5 / 79 (6.33%)
    1 / 79 (1.27%)
    10 / 80 (12.50%)
    7 / 45 (15.56%)
    2 / 45 (4.44%)
    3 / 43 (6.98%)
         occurrences all number
    1
    5
    5
    5
    1
    11
    7
    2
    3
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    1 / 80 (1.25%)
    2 / 41 (4.88%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    1 / 79 (1.27%)
    5 / 80 (6.25%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    1 / 43 (2.33%)
         occurrences all number
    1
    2
    2
    1
    1
    5
    1
    1
    1
    Anxiety
         subjects affected / exposed
    2 / 80 (2.50%)
    2 / 41 (4.88%)
    0 / 79 (0.00%)
    3 / 79 (3.80%)
    4 / 79 (5.06%)
    6 / 80 (7.50%)
    4 / 45 (8.89%)
    1 / 45 (2.22%)
    3 / 43 (6.98%)
         occurrences all number
    3
    2
    0
    3
    4
    6
    4
    1
    4
    Depressed mood
         subjects affected / exposed
    1 / 80 (1.25%)
    3 / 41 (7.32%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    1 / 43 (2.33%)
         occurrences all number
    1
    3
    1
    0
    0
    0
    0
    2
    1
    Depression
         subjects affected / exposed
    3 / 80 (3.75%)
    3 / 41 (7.32%)
    3 / 79 (3.80%)
    1 / 79 (1.27%)
    3 / 79 (3.80%)
    12 / 80 (15.00%)
    2 / 45 (4.44%)
    5 / 45 (11.11%)
    1 / 43 (2.33%)
         occurrences all number
    3
    3
    3
    1
    4
    13
    2
    5
    1
    Insomnia
         subjects affected / exposed
    10 / 80 (12.50%)
    8 / 41 (19.51%)
    9 / 79 (11.39%)
    6 / 79 (7.59%)
    16 / 79 (20.25%)
    20 / 80 (25.00%)
    8 / 45 (17.78%)
    6 / 45 (13.33%)
    7 / 43 (16.28%)
         occurrences all number
    10
    8
    9
    6
    17
    22
    8
    6
    8
    Sleep disorder
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    0 / 79 (0.00%)
    2 / 80 (2.50%)
    0 / 45 (0.00%)
    4 / 45 (8.89%)
    2 / 43 (4.65%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    0
    4
    2
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    1 / 79 (1.27%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    4 / 43 (9.30%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    1
    4
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 80 (6.25%)
    1 / 41 (2.44%)
    3 / 79 (3.80%)
    1 / 79 (1.27%)
    7 / 79 (8.86%)
    6 / 80 (7.50%)
    3 / 45 (6.67%)
    3 / 45 (6.67%)
    2 / 43 (4.65%)
         occurrences all number
    5
    1
    3
    1
    7
    6
    3
    3
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    12 / 80 (15.00%)
    5 / 41 (12.20%)
    11 / 79 (13.92%)
    2 / 79 (2.53%)
    8 / 79 (10.13%)
    12 / 80 (15.00%)
    7 / 45 (15.56%)
    3 / 45 (6.67%)
    9 / 43 (20.93%)
         occurrences all number
    12
    5
    11
    2
    8
    14
    7
    3
    12
    Dyspnoea
         subjects affected / exposed
    8 / 80 (10.00%)
    3 / 41 (7.32%)
    4 / 79 (5.06%)
    1 / 79 (1.27%)
    5 / 79 (6.33%)
    8 / 80 (10.00%)
    4 / 45 (8.89%)
    3 / 45 (6.67%)
    3 / 43 (6.98%)
         occurrences all number
    8
    3
    4
    1
    5
    8
    4
    3
    4
    Dyspnoea exertional
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 41 (0.00%)
    3 / 79 (3.80%)
    0 / 79 (0.00%)
    4 / 79 (5.06%)
    9 / 80 (11.25%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    2
    0
    3
    0
    4
    11
    0
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    3 / 80 (3.75%)
    0 / 41 (0.00%)
    4 / 79 (5.06%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    4 / 80 (5.00%)
    2 / 45 (4.44%)
    4 / 45 (8.89%)
    2 / 43 (4.65%)
         occurrences all number
    3
    0
    4
    0
    1
    4
    3
    4
    2
    Sinus congestion
         subjects affected / exposed
    4 / 80 (5.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    1 / 79 (1.27%)
    2 / 80 (2.50%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    4
    0
    0
    1
    1
    2
    1
    0
    0
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    2 / 80 (2.50%)
    1 / 41 (2.44%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    2 / 79 (2.53%)
    9 / 80 (11.25%)
    3 / 45 (6.67%)
    3 / 45 (6.67%)
    3 / 43 (6.98%)
         occurrences all number
    2
    1
    2
    1
    2
    9
    4
    3
    4
    Dizziness
         subjects affected / exposed
    5 / 80 (6.25%)
    7 / 41 (17.07%)
    2 / 79 (2.53%)
    4 / 79 (5.06%)
    3 / 79 (3.80%)
    8 / 80 (10.00%)
    4 / 45 (8.89%)
    1 / 45 (2.22%)
    4 / 43 (9.30%)
         occurrences all number
    5
    8
    2
    4
    3
    8
    4
    1
    5
    Dysgeusia
         subjects affected / exposed
    2 / 80 (2.50%)
    1 / 41 (2.44%)
    3 / 79 (3.80%)
    2 / 79 (2.53%)
    3 / 79 (3.80%)
    4 / 80 (5.00%)
    0 / 45 (0.00%)
    4 / 45 (8.89%)
    4 / 43 (9.30%)
         occurrences all number
    2
    1
    3
    2
    3
    4
    0
    4
    4
    Headache
         subjects affected / exposed
    28 / 80 (35.00%)
    13 / 41 (31.71%)
    23 / 79 (29.11%)
    15 / 79 (18.99%)
    21 / 79 (26.58%)
    28 / 80 (35.00%)
    15 / 45 (33.33%)
    13 / 45 (28.89%)
    14 / 43 (32.56%)
         occurrences all number
    31
    18
    30
    15
    22
    29
    17
    13
    20
    Lethargy
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    1 / 80 (1.25%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    2
    1
    0
    1
    1
    4
    2
    Memory impairment
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
    3 / 79 (3.80%)
    0 / 79 (0.00%)
    5 / 80 (6.25%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    1
    3
    0
    5
    1
    0
    2
    Paraesthesia
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    3 / 79 (3.80%)
    1 / 79 (1.27%)
    1 / 79 (1.27%)
    2 / 80 (2.50%)
    1 / 45 (2.22%)
    0 / 45 (0.00%)
    5 / 43 (11.63%)
         occurrences all number
    0
    0
    3
    1
    1
    2
    1
    0
    5
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 80 (1.25%)
    3 / 41 (7.32%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    3 / 80 (3.75%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    3
    3
    0
    1
    0
    3
    0
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 41 (2.44%)
    1 / 79 (1.27%)
    3 / 79 (3.80%)
    3 / 79 (3.80%)
    5 / 80 (6.25%)
    0 / 45 (0.00%)
    2 / 45 (4.44%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    1
    3
    3
    5
    0
    2
    0
    Abdominal pain
         subjects affected / exposed
    1 / 80 (1.25%)
    3 / 41 (7.32%)
    4 / 79 (5.06%)
    3 / 79 (3.80%)
    3 / 79 (3.80%)
    7 / 80 (8.75%)
    1 / 45 (2.22%)
    6 / 45 (13.33%)
    0 / 43 (0.00%)
         occurrences all number
    1
    3
    4
    4
    4
    8
    1
    7
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 80 (0.00%)
    2 / 41 (4.88%)
    5 / 79 (6.33%)
    3 / 79 (3.80%)
    4 / 79 (5.06%)
    4 / 80 (5.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    2 / 43 (4.65%)
         occurrences all number
    0
    2
    5
    3
    4
    4
    0
    1
    2
    Constipation
         subjects affected / exposed
    3 / 80 (3.75%)
    1 / 41 (2.44%)
    5 / 79 (6.33%)
    5 / 79 (6.33%)
    1 / 79 (1.27%)
    9 / 80 (11.25%)
    2 / 45 (4.44%)
    1 / 45 (2.22%)
    4 / 43 (9.30%)
         occurrences all number
    4
    1
    5
    5
    2
    11
    2
    2
    4
    Diarrhoea
         subjects affected / exposed
    8 / 80 (10.00%)
    10 / 41 (24.39%)
    8 / 79 (10.13%)
    13 / 79 (16.46%)
    10 / 79 (12.66%)
    11 / 80 (13.75%)
    7 / 45 (15.56%)
    8 / 45 (17.78%)
    8 / 43 (18.60%)
         occurrences all number
    8
    12
    8
    15
    11
    13
    9
    10
    12
    Dry mouth
         subjects affected / exposed
    4 / 80 (5.00%)
    0 / 41 (0.00%)
    2 / 79 (2.53%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    2 / 80 (2.50%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
    2 / 43 (4.65%)
         occurrences all number
    4
    0
    3
    2
    1
    2
    1
    2
    2
    Dyspepsia
         subjects affected / exposed
    7 / 80 (8.75%)
    1 / 41 (2.44%)
    9 / 79 (11.39%)
    2 / 79 (2.53%)
    4 / 79 (5.06%)
    6 / 80 (7.50%)
    2 / 45 (4.44%)
    2 / 45 (4.44%)
    2 / 43 (4.65%)
         occurrences all number
    8
    1
    9
    2
    4
    6
    3
    2
    2
    Flatulence
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 41 (2.44%)
    4 / 79 (5.06%)
    4 / 79 (5.06%)
    2 / 79 (2.53%)
    1 / 80 (1.25%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    4
    4
    2
    1
    0
    1
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 41 (0.00%)
    2 / 79 (2.53%)
    3 / 79 (3.80%)
    2 / 79 (2.53%)
    2 / 80 (2.50%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    4 / 43 (9.30%)
         occurrences all number
    1
    0
    2
    3
    2
    2
    1
    1
    4
    Nausea
         subjects affected / exposed
    12 / 80 (15.00%)
    7 / 41 (17.07%)
    16 / 79 (20.25%)
    11 / 79 (13.92%)
    19 / 79 (24.05%)
    20 / 80 (25.00%)
    6 / 45 (13.33%)
    9 / 45 (20.00%)
    8 / 43 (18.60%)
         occurrences all number
    13
    9
    16
    12
    21
    23
    6
    11
    8
    Vomiting
         subjects affected / exposed
    7 / 80 (8.75%)
    4 / 41 (9.76%)
    4 / 79 (5.06%)
    4 / 79 (5.06%)
    4 / 79 (5.06%)
    4 / 80 (5.00%)
    4 / 45 (8.89%)
    4 / 45 (8.89%)
    3 / 43 (6.98%)
         occurrences all number
    8
    4
    4
    4
    5
    5
    4
    4
    3
    Hepatobiliary disorders
    Jaundice
         subjects affected / exposed
    3 / 80 (3.75%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    3 / 79 (3.80%)
    3 / 80 (3.75%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
    1 / 43 (2.33%)
         occurrences all number
    3
    0
    1
    0
    3
    3
    1
    3
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 80 (0.00%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    2 / 79 (2.53%)
    0 / 79 (0.00%)
    6 / 80 (7.50%)
    0 / 45 (0.00%)
    0 / 45 (0.00%)
    4 / 43 (9.30%)
         occurrences all number
    0
    0
    0
    2
    0
    7
    0
    0
    4
    Dry skin
         subjects affected / exposed
    4 / 80 (5.00%)
    3 / 41 (7.32%)
    3 / 79 (3.80%)
    1 / 79 (1.27%)
    4 / 79 (5.06%)
    6 / 80 (7.50%)
    6 / 45 (13.33%)
    4 / 45 (8.89%)
    4 / 43 (9.30%)
         occurrences all number
    4
    4
    3
    1
    4
    7
    6
    4
    4
    Pruritus
         subjects affected / exposed
    12 / 80 (15.00%)
    3 / 41 (7.32%)
    8 / 79 (10.13%)
    3 / 79 (3.80%)
    6 / 79 (7.59%)
    11 / 80 (13.75%)
    6 / 45 (13.33%)
    7 / 45 (15.56%)
    6 / 43 (13.95%)
         occurrences all number
    13
    3
    10
    3
    6
    12
    8
    7
    6
    Pruritus generalised
         subjects affected / exposed
    2 / 80 (2.50%)
    5 / 41 (12.20%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    4 / 79 (5.06%)
    3 / 80 (3.75%)
    5 / 45 (11.11%)
    0 / 45 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    2
    5
    0
    2
    4
    3
    6
    0
    1
    Rash
         subjects affected / exposed
    10 / 80 (12.50%)
    2 / 41 (4.88%)
    6 / 79 (7.59%)
    6 / 79 (7.59%)
    11 / 79 (13.92%)
    15 / 80 (18.75%)
    2 / 45 (4.44%)
    4 / 45 (8.89%)
    6 / 43 (13.95%)
         occurrences all number
    12
    2
    8
    6
    11
    18
    5
    4
    6
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 80 (2.50%)
    2 / 41 (4.88%)
    6 / 79 (7.59%)
    7 / 79 (8.86%)
    5 / 79 (6.33%)
    8 / 80 (10.00%)
    3 / 45 (6.67%)
    5 / 45 (11.11%)
    7 / 43 (16.28%)
         occurrences all number
    2
    3
    6
    8
    6
    9
    3
    5
    7
    Back pain
         subjects affected / exposed
    2 / 80 (2.50%)
    1 / 41 (2.44%)
    3 / 79 (3.80%)
    4 / 79 (5.06%)
    2 / 79 (2.53%)
    5 / 80 (6.25%)
    2 / 45 (4.44%)
    2 / 45 (4.44%)
    4 / 43 (9.30%)
         occurrences all number
    2
    1
    3
    4
    2
    5
    3
    2
    4
    Muscle spasms
         subjects affected / exposed
    2 / 80 (2.50%)
    1 / 41 (2.44%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    5 / 79 (6.33%)
    2 / 80 (2.50%)
    2 / 45 (4.44%)
    0 / 45 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    2
    1
    2
    1
    5
    2
    2
    0
    0
    Myalgia
         subjects affected / exposed
    4 / 80 (5.00%)
    3 / 41 (7.32%)
    5 / 79 (6.33%)
    2 / 79 (2.53%)
    3 / 79 (3.80%)
    9 / 80 (11.25%)
    5 / 45 (11.11%)
    4 / 45 (8.89%)
    6 / 43 (13.95%)
         occurrences all number
    4
    3
    5
    2
    3
    10
    5
    4
    7
    Pain in extremity
         subjects affected / exposed
    2 / 80 (2.50%)
    1 / 41 (2.44%)
    1 / 79 (1.27%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    3 / 80 (3.75%)
    0 / 45 (0.00%)
    3 / 45 (6.67%)
    0 / 43 (0.00%)
         occurrences all number
    2
    1
    1
    1
    0
    3
    0
    3
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    8 / 80 (10.00%)
    1 / 41 (2.44%)
    5 / 79 (6.33%)
    3 / 79 (3.80%)
    3 / 79 (3.80%)
    6 / 80 (7.50%)
    3 / 45 (6.67%)
    1 / 45 (2.22%)
    1 / 43 (2.33%)
         occurrences all number
    8
    1
    5
    3
    3
    7
    3
    1
    2
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 41 (0.00%)
    1 / 79 (1.27%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    1 / 80 (1.25%)
    1 / 45 (2.22%)
    3 / 45 (6.67%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    1
    2
    2
    1
    1
    3
    0
    Nasopharyngitis
         subjects affected / exposed
    4 / 80 (5.00%)
    3 / 41 (7.32%)
    4 / 79 (5.06%)
    8 / 79 (10.13%)
    7 / 79 (8.86%)
    7 / 80 (8.75%)
    2 / 45 (4.44%)
    4 / 45 (8.89%)
    3 / 43 (6.98%)
         occurrences all number
    4
    3
    4
    8
    7
    8
    2
    4
    4
    Oral herpes
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 41 (0.00%)
    2 / 79 (2.53%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    3 / 80 (3.75%)
    3 / 45 (6.67%)
    3 / 45 (6.67%)
    2 / 43 (4.65%)
         occurrences all number
    3
    0
    2
    2
    1
    3
    5
    4
    2
    Rhinitis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 41 (0.00%)
    5 / 79 (6.33%)
    2 / 79 (2.53%)
    0 / 79 (0.00%)
    0 / 80 (0.00%)
    0 / 45 (0.00%)
    1 / 45 (2.22%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    6
    2
    0
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    4 / 80 (5.00%)
    0 / 41 (0.00%)
    7 / 79 (8.86%)
    2 / 79 (2.53%)
    5 / 79 (6.33%)
    3 / 80 (3.75%)
    1 / 45 (2.22%)
    2 / 45 (4.44%)
    3 / 43 (6.98%)
         occurrences all number
    4
    0
    8
    2
    5
    3
    1
    2
    3
    Tooth infection
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 41 (0.00%)
    0 / 79 (0.00%)
    1 / 79 (1.27%)
    4 / 79 (5.06%)
    4 / 80 (5.00%)
    1 / 45 (2.22%)
    1 / 45 (2.22%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    0
    1
    4
    4
    1
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 80 (6.25%)
    1 / 41 (2.44%)
    5 / 79 (6.33%)
    5 / 79 (6.33%)
    4 / 79 (5.06%)
    5 / 80 (6.25%)
    3 / 45 (6.67%)
    4 / 45 (8.89%)
    0 / 43 (0.00%)
         occurrences all number
    5
    2
    5
    5
    4
    5
    3
    4
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 80 (5.00%)
    3 / 41 (7.32%)
    2 / 79 (2.53%)
    1 / 79 (1.27%)
    0 / 79 (0.00%)
    6 / 80 (7.50%)
    2 / 45 (4.44%)
    3 / 45 (6.67%)
    2 / 43 (4.65%)
         occurrences all number
    4
    3
    2
    2
    0
    6
    2
    4
    2

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Oct 2011
    The purpose of this amendment was to: ● modify the post-treatment pregnancy monitoring to be in compliance with local labeling requirements for RBV; ● clarify that the RBV Pregnancy Registry Brochure and RBV Medication Guide were to be distributed where applicable/locally available; ● define the primary and secondary endpoints of SVR24 as HCV RNA < LLOQ 24 weeks after the last dose of study drug; ● incorporate Administrative Change 1; and ● address inconsistencies throughout the protocol

    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.
    None reported
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