Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43870   clinical trials with a EudraCT protocol, of which   7289   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3 Study with Asunaprevir and Daclatasvir (DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant or Ineligible to P/R Subjects and Treatment- Naive Subjects with Chronic Hepatitis C Genotype 1b Infection.

    Summary
    EudraCT number
    		 2011-005446-35
    Trial protocol
    		 IE   AT   GB   NL   ES   DE   IT  
    Global end of trial date
    20 Sep 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Jul 2016
    First version publication date
    01 Jul 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    AI447-028
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01581203
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussee de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, clinical.trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, clinical.trials@bms.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
    20 Sep 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    For the prior null or partial responders to peginterferon alfa and ribavirin (pegIFN alfa/ribavirin) cohort: To estimate efficacy, as determined by the proportion of subjects with sustained virologic response at post-treatment Week 12 (SVR12), defined as hepatitis C virus (HCV) RNA <limit of quantitation at post-treatment Week 12. For the treatment naive cohort: To determine whether the SVR12 rate in subjects treated with daclatasvir/asunaprevir therapy is similar to the historical SVR rate for telaprevir in combination with pegIFN alfa/ribavirin in previously untreated, genotype 1b, HCV subjects.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 May 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 25
    Country: Number of subjects enrolled
    Austria: 37
    Country: Number of subjects enrolled
    Australia: 89
    Country: Number of subjects enrolled
    Canada: 57
    Country: Number of subjects enrolled
    France: 118
    Country: Number of subjects enrolled
    Germany: 76
    Country: Number of subjects enrolled
    Ireland: 9
    Country: Number of subjects enrolled
    Israel: 24
    Country: Number of subjects enrolled
    Italy: 21
    Country: Number of subjects enrolled
    Korea, Republic of: 92
    Country: Number of subjects enrolled
    Netherlands: 19
    Country: Number of subjects enrolled
    New Zealand: 8
    Country: Number of subjects enrolled
    Poland: 7
    Country: Number of subjects enrolled
    Russian Federation: 34
    Country: Number of subjects enrolled
    Spain: 24
    Country: Number of subjects enrolled
    Taiwan: 121
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    United States: 190
    Worldwide total number of subjects
    975
    EEA total number of subjects
    335
    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)
    784
    From 65 to 84 years
    191
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 116 sites in 18 countries.

    Pre-assignment
    Screening details
    		 A total of 975 subjects were enrolled, of which 747 were treated. Remaining 228 subjects did not receive any treatment; Reasons: no longer met the study criteria-192, subject withdrew consent to participate-29; other reasons-7.

    Period 1
    Period 1 title
    Treatment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Randomized treatment assignment in the treatment naive cohort was placebo-controlled and investigator site, subject and sponsor were blinded until the Week 12 visit.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir
    Arm description
    		 Subjects with Hepatitis C virus genotype 1b, null or partial responder to peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Asunaprevir
    Investigational medicinal product code
    BMS-650032
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Asunaprevir 100-mg softgel capsule was administered twice daily.

    Investigational medicinal product name
    Daclatasvir
    Investigational medicinal product code
    BMS-790052
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daclatasvir 60-mg film coated tablet was administered once daily.

    Arm title
    		 Intolerant or Ineligible: Asunaprevir+ Daclatasvir
    Arm description
    		 Subjects with Hepatitis C virus genotype 1b, intolerant to or ineligible for peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daclatasvir
    Investigational medicinal product code
    BMS-790052
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daclatasvir 60-mg film coated tablet was administered once daily.

    Investigational medicinal product name
    Asunaprevir
    Investigational medicinal product code
    BMS-650032
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Asunaprevir 100-mg softgel capsule was administered twice daily.

    Arm title
    		 Treatment-naive: Asunaprevir+ Daclatasvir
    Arm description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received daclatasvir 60 mg orally once daily, asunaprevir 100 mg twice daily for up to 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daclatasvir
    Investigational medicinal product code
    BMS-790052
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daclatasvir 60-mg film coated tablet was administered orally once daily.

    Investigational medicinal product name
    Asunaprevir
    Investigational medicinal product code
    BMS-650032
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Asunaprevir 100-mg softgel capsule was administered orally twice daily.

    Arm title
    		 Treatment-naive: Placebo for Asunaprevir + Daclatasvir
    Arm description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received placebo of daclatasvir once daily and placebo of asunaprevir twice daily for 12 weeks. Subjects were then entered in study NCT01428063 where they receive daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily for 24 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo (for Daclatasvir)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to daclatasvir was administered once daily.

    Investigational medicinal product name
    Placebo (for Asunaprevir)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to asunaprevir was administered twice daily.

    Number of subjects in period 1 [1]
    		Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir Treatment-naive: Placebo for Asunaprevir + Daclatasvir
    Started
    205
    235
    205
    102
    Completed
    177
    208
    190
    102
    Not completed
    28
    27
    15
    0
         Consent withdrawn by subject
    -
    4
    -
    -
         Adverse event, non-fatal
    2
    2
    6
    -
         Subject request to discontinue study treatment
    -
    1
    -
    -
         Lost to follow-up
    -
    -
    1
    -
         Lack of efficacy
    26
    20
    8
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of 975 subjects who were enrolled, only 747 were treated. Remaining 228 subjects did not receive any treatment. 192 subjects no longer met the study criteria, 29 subjects withdrew consent to participate, and 7 due to other reasons.
    Period 2
    Period 2 title
    Follow-up Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir
    Arm description
    		 Subjects with Hepatitis C virus genotype 1b, null or partial responder to peginterferon alfa and ribavirin received daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily for 24 weeks. Subjects were followed for 24 weeks of follow-up after completion of treatment or upon early discontinuation of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daclatasvir
    Investigational medicinal product code
    BMS-790052
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daclatasvir 60-mg film coated tablet was administered once daily.

    Investigational medicinal product name
    Asunaprevir
    Investigational medicinal product code
    BMS-650032
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Asunaprevir 100-mg softgel capsule was administered twice daily.

    Arm title
    		 Intolerant or Ineligible: Asunaprevir+ Daclatasvir
    Arm description
    		 Subjects with Hepatitis C virus genotype 1b, intolerant to or ineligible for peginterferon alfa and ribavirin received daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily for 24 weeks. Subjects were followed for 24 weeks of follow-up after completion of treatment or upon early discontinuation of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Asunaprevir
    Investigational medicinal product code
    BMS-650032
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Asunaprevir 100-mg softgel capsule was administered twice daily.

    Investigational medicinal product name
    Daclatasvir
    Investigational medicinal product code
    BMS-790052
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daclatasvir 60-mg film coated tablet was administered once daily.

    Arm title
    		 Treatment-naive: Asunaprevir+ Daclatasvir
    Arm description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received daclatasvir 60 mg orally once daily, asunaprevir 100 mg twice daily for up to 24 weeks. Subjects were then followed for 24 weeks of follow-up after completion of treatment or upon early discontinuation of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Asunaprevir
    Investigational medicinal product code
    BMS-650032
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Asunaprevir 100-mg softgel capsule was administered orally twice daily.

    Investigational medicinal product name
    Daclatasvir
    Investigational medicinal product code
    BMS-790052
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daclatasvir 60-mg film coated tablet was administered orally once daily.

    Number of subjects in period 2 [2]
    		Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Started
    203
    230
    204
    Completed
    202
    228
    204
    Not completed
    1
    2
    0
         Consent withdrawn by subject
    1
    1
    -
         Lost to follow-up
    -
    1
    -
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The number of subjects starting the follow-up period includes those completing previous period plus those that re-joined for followup.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Prior Null or partial responder: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, null or partial responder to peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.

    Reporting group title
    Intolerant or Ineligible: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, intolerant to or ineligible for peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.

    Reporting group title
    Treatment-naive: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received daclatasvir 60 mg orally once daily, asunaprevir 100 mg twice daily for up to 24 weeks.

    Reporting group title
    Treatment-naive: Placebo for Asunaprevir + Daclatasvir
    Reporting group description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received placebo of daclatasvir once daily and placebo of asunaprevir twice daily for 12 weeks. Subjects were then entered in study NCT01428063 where they receive daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily for 24 weeks.

    Reporting group values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir Treatment-naive: Placebo for Asunaprevir + Daclatasvir Total
    Number of subjects
    		 205 235 205 102 747
    Age categorical
    Units: Subjects
        <65 years
    		 161 175 176 84 596
        >=65 years
    		 44 60 29 18 151
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.1 ( 10.51 ) 58 ( 9.94 ) 53.1 ( 11.69 ) 52.5 ( 12.89 ) -
    Gender categorical
    Units: Subjects
        Female
    		 94 137 104 48 383
        Male
    		 111 98 101 54 364

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Prior Null or partial responder: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, null or partial responder to peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.

    Reporting group title
    Intolerant or Ineligible: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, intolerant to or ineligible for peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.

    Reporting group title
    Treatment-naive: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received daclatasvir 60 mg orally once daily, asunaprevir 100 mg twice daily for up to 24 weeks.

    Reporting group title
    Treatment-naive: Placebo for Asunaprevir + Daclatasvir
    Reporting group description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received placebo of daclatasvir once daily and placebo of asunaprevir twice daily for 12 weeks. Subjects were then entered in study NCT01428063 where they receive daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily for 24 weeks.
    Reporting group title
    Prior Null or partial responder: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, null or partial responder to peginterferon alfa and ribavirin received daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily for 24 weeks. Subjects were followed for 24 weeks of follow-up after completion of treatment or upon early discontinuation of treatment.

    Reporting group title
    Intolerant or Ineligible: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, intolerant to or ineligible for peginterferon alfa and ribavirin received daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily for 24 weeks. Subjects were followed for 24 weeks of follow-up after completion of treatment or upon early discontinuation of treatment.

    Reporting group title
    Treatment-naive: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received daclatasvir 60 mg orally once daily, asunaprevir 100 mg twice daily for up to 24 weeks. Subjects were then followed for 24 weeks of follow-up after completion of treatment or upon early discontinuation of treatment.

    Primary: Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects Who Were Prior Null or Partial Responders to Peginterferon Alfa/Ribavirin or Treatment Naive Achieving Sustained Virologic Response at Follow-Up Week 12 (SVR12)

    		 Close Top of page
    End point title
    		 Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects Who Were Prior Null or Partial Responders to Peginterferon Alfa/Ribavirin or Treatment Naive Achieving Sustained Virologic Response at Follow-Up Week 12 (SVR12) [1] [2]
    End point description
    Sustained Virologic Response at Post-Treatment Week 12 was defined as hepatitis C Virus (HCV) RNA levels to be <lower limit of quantitation i.e., 25 international unit per milliliter, target detected or target not detected, at follow-up Week 12 for subjects who were prior null or partial responders to Peginterferon Alfa/Ribavirin or were treatment-naive. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. The analysis was performed in all genotype 1b subjects who received at least 1 dose of study therapy, active or placebo. For subjects who missed the follow-up Week 12 visit, SVR12 was imputed using the first available HCV RNA measurement after the follow-up Week 12 window.
    End point type
    Primary
    End point timeframe
    Follow-Up Week 12
    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: Only descriptive summary statistics were planned for this outcome measure.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    203
    Units: Percentage of Subjects
        number (confidence interval 95%)
    82.4 (77.2 to 87.6)
    91.1 (87.2 to 95)
    No statistical analyses for this end point

    Secondary: Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects Who Were Intolerant to or Ineligible For Peginterferon Alfa/Ribavirin Achieving Sustained Virologic Response at Follow-Up Week 12 (SVR12)

    		 Close Top of page
    End point title
    		 Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects Who Were Intolerant to or Ineligible For Peginterferon Alfa/Ribavirin Achieving Sustained Virologic Response at Follow-Up Week 12 (SVR12) [3]
    End point description
    SVR12 rate was defined as hepatitis C Virus (HCV) RNA levels to be <lower limit of quantitation i.e., 25 international unit per milliliter target detected or target not detected, at follow-up Week 12 for subjects who were intolerant to or ineligible for Peginterferon Alfa/Ribavirin (pegIFNalfa/RBV). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. All genotype 1b subjects who received at least 1 dose of study therapy, active or placebo. For subjects who missed the follow-up Week 12 visit, SVR12 was imputed using the first available HCV RNA measurement after the follow-up Week 12 window.
    End point type
    Secondary
    End point timeframe
    Follow-Up Week 12
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Intolerant or Ineligible: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    235
    Units: Percentage of subjects
        number (confidence interval 95%)
    82.6 (77.7 to 87.4)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Anaemia

    		 Close Top of page
    End point title
    		 Percentage of Subjects with Anaemia [4]
    End point description
    Anaemia was defined as the decline in hemoglobin levels below 10 gram/deciliter. The analysis was performed on all treated subjects who received at least 1 dose of study therapy. Number of subjects analysed refers to number of subjects that were evaluable for this outcome measure on treatment.
    End point type
    Secondary
    End point timeframe
    From start of study treatment up to 7 days post last dose of study treatment
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    234
    203
    Units: Percentage of Subjects
        number (not applicable)
    1.5
    3
    1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Rash Events

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Rash Events [5]
    End point description
    Rash was defined as occurrence of dermatitis allergic, vasculitic rash, eczema, purpura, petechiae, dermatitis acneiform, ecchymosis, gingival disorder, cheilitis, pemphigoid, acute generalized exanthematous pustulosis, dermatitis, dermatitis bullous/exfoliative/exfoliative generalised, drug eruption, drug rash with eosinophilia and systemic symptoms, erythema multiforme, fixed eruption, haemorrhagic urticaria, idiopathic urticaria, exfoliative/genital/mucocutaneous rash, oral mucosal eruption, urticarial, rash erythematous/follicular/generalized/macular/maculo-papular/ maculovesicular/morbilliform/popular/papulosquamous/pruritic/pustular/vesicular, septic rash, Stevens-Johnson syndrome, tongue eruption, toxic epidermal necrolysis, toxic skin eruption, and urticaria popular. The analysis was performed on all treated subjects who received at least 1 dose of study therapy. Number of subjects analysed signifies subjects evaluable for this outcome measure on treatment.
    End point type
    Secondary
    End point timeframe
    From start of study treatment up to 7 days post last dose of study treatment
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    235
    205
    Units: Percentage of Subjects
        number (not applicable)
    5.4
    8.1
    7.8
    No statistical analyses for this end point

    Secondary: Number of Subjects With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Grade 3 to 4 AEs, and Who Died During Treatment Period

    		 Close Top of page
    End point title
    		 Number of Subjects With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Grade 3 to 4 AEs, and Who Died During Treatment Period [6]
    End point description
    AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not has a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalisation. Grade 3 to 4 AE were also reported. The analysis was performed on all treated subjects who received at least 1 dose of study therapy.
    End point type
    Secondary
    End point timeframe
    From start of study treatment up to 7 days post last dose of study treatment
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    235
    205
    Units: Subjects
    number (not applicable)
        SAEs
    11
    16
    12
        AEs Leading to Discontinuation
    2
    2
    6
        Grade 3/4 AEs
    15
    21
    14
        Death
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Genotype 1b Chronic Hepatitis C Infected Treatment-naive Subjects With Selected Grade 3-4 Laboratory Abnormalities During the First 12 Weeks of Treatment

    		 Close Top of page
    End point title
    		 Percentage of Genotype 1b Chronic Hepatitis C Infected Treatment-naive Subjects With Selected Grade 3-4 Laboratory Abnormalities During the First 12 Weeks of Treatment [7]
    End point description
    Clinically significant changes in laboratory abnormalities were defined as Hemoglobin as 6.50–7.4 g/dL for grade 3 and/or <6.5 g/dL for grade 4, absolute neutrophil count for Grade 3 <1.0 to 0.5*10^9/L, Grade 4 <0.5*10^9/L. Alanine aminotransferase as 5.1–10.0* ULN for grade 3 and/or > 10.0* (upper limit of normal) ULN for grade 4, Aspartate aminotransferase as 5.1–10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Bilirubin (Total) as 2.6–5.0*ULN for grade 3 and/or > 5.0*ULN for grade 4. The analysis was performed on all treated subjects who received at least 1 dose of study therapy. Here, ‘Number of subjects analysed’ signifies the subjects evaluable for this outcome at week 12.
    End point type
    Secondary
    End point timeframe
    Through Week 12
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Treatment-naive: Asunaprevir+ Daclatasvir Treatment-naive: Placebo for Asunaprevir + Daclatasvir
    Number of subjects analysed
    203
    102
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Hemoglobin
    0 (0 to 0)
    1 (0 to 2.9)
        Neutrophils + Bands
    1 (0 to 2.3)
    1 (0 to 2.9)
        Alanine Aminotransferase
    2 (0.1 to 3.9)
    2 (0 to 4.7)
        Aspartate Aminotransferase
    1.5 (0 to 3.1)
    1 (0 to 2.9)
        Bilirubin Total
    0 (0 to 0)
    1 (0 to 2.9)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL28B Gene

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL28B Gene [8]
    End point description
    SVR12 rate was defined as HCV RNA levels to be < lower limit of quantitation i.e., 25 international unit per milliliter, target detected or target not detected at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. SNP included wild type (common homozygous), mixed (heterozygous), mutant (minor homozygous). Here ‘n’ specify the number of subjects analysed for specified time point in each group, respectively. The analysis was performed on all treated subjects who received at least 1 dose of study therapy.
    End point type
    Secondary
    End point timeframe
    Post-treatment Week 12
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    235
    203
    Units: Percentage of Subjects
    number (confidence interval 80%)
        CC wild type (n= 29, 82, 76)
    75.9 (65.7 to 86)
    80.5 (74.9 to 86.1)
    89.5 (85 to 94)
        CT heterozygous (n= 123, 102, 99)
    81.3 (76.8 to 85.8)
    81.4 (76.4 to 86.3)
    87.9 (83.7 to 92.1)
        TT minor homozygous (n= 50, 41, 28)
    86 (79.7 to 92.3)
    87.8 (81.3 to 94.4)
    96.4 (91.9 to 100)
        Not reported (n=3, 10, 0)
    100 (100 to 100)
    70 (51.4 to 88.6)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects With Hepatitis C Virus (HCV) RNA <Lower Limit of Quantitation (LLOQ), Target not Detected

    		 Close Top of page
    End point title
    		 Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects With Hepatitis C Virus (HCV) RNA <Lower Limit of Quantitation (LLOQ), Target not Detected [9]
    End point description
    HCV RNA levels to be <LLOQ i.e. 25 international unit per milliliter, target not detected. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. The analysis was performed on all treated subjects who received at least 1 dose of study therapy. Here, ‘99999’ represents not estimable data for specified categories in respective arms. .
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24, follow-up week 12, and follow-up week 24
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    235
    203
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Baseline
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
        Week 2
    16.1 (11.1 to 21.1)
    19.1 (14.1 to 24.2)
    27.6 (21.4 to 33.7)
        Week 4
    73.2 (67.1 to 79.2)
    67.7 (61.7 to 73.6)
    82.8 (77.6 to 88)
        Week 6
    90.2 (86.2 to 94.3)
    84.7 (80.1 to 89.3)
    89.7 (85.5 to 93.8)
        Week 8
    88.8 (84.5 to 93.1)
    88.9 (84.9 to 92.9)
    96.6 (94 to 99.1)
        Week 10
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    88.2 (83.7 to 92.6)
        Week 12
    88.8 (84.5 to 93.1)
    87.2 (83 to 91.5)
    94.1 (90.8 to 97.3)
        Week 16
    87.8 (83.3 to 92.3)
    86.8 (82.5 to 91.1)
    92.6 (89 to 96.2)
        Week 20
    83.9 (78.9 to 88.9)
    86.8 (82.5 to 91.1)
    90.1 (86 to 94.2)
        Week 24
    83.4 (78.3 to 88.5)
    83.8 (79.1 to 88.5)
    88.7 (84.3 to 93)
        Follow-up Week 12
    81.5 (76.1 to 86.8)
    78.7 (73.5 to 84)
    88.7 (84.3 to 93)
        Follow-up Week 24
    80.5 (75.1 to 85.9)
    80.9 (75.8 to 85.9)
    90.1 (86 to 94.2)
    No statistical analyses for this end point

    Secondary: Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects with Hepatitis C Virus (HCV) RNA <Lower Limit of Quantitation (LLOQ), Target Detected or Target not Detected

    		 Close Top of page
    End point title
    		 Percentage of Genotype 1b Chronic Hepatitis C Infected Subjects with Hepatitis C Virus (HCV) RNA <Lower Limit of Quantitation (LLOQ), Target Detected or Target not Detected [10]
    End point description
    HCV RNA levels to be <LLOQ i.e., 25 international unit per milliliter, target detected or target not detected. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. The analysis was performed on all treated subjects who received at least 1 dose of study therapy. Here, ‘99999’ represents not estimable data for specified categories in respective arms.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24 and follow-up Week 24
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    235
    203
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Baseline
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
        Week 2
    64.9 (58.3 to 71.4)
    68.1 (62.1 to 74)
    81.3 (75.9 to 86.6)
        Week 4
    96.6 (94.1 to 99.1)
    91.9 (88.4 to 95.4)
    97 (94.7 to 99.4)
        Week 6
    94.1 (90.9 to 97.4)
    92.3 (88.9 to 95.7)
    94.6 (91.5 to 97.7)
        Week 8
    92.7 (89.1 to 96.2)
    91.9 (88.4 to 95.4)
    97.5 (95.4 to 99.7)
        Week 10
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    89.2 (84.9 to 93.4)
        Week 12
    91.2 (87.3 to 95.1)
    91.1 (87.4 to 94.7)
    96.6 (94 to 99.1)
        Week 16
    90.2 (86.2 to 94.3)
    89.8 (85.9 to 93.7)
    94.6 (91.5 to 97.7)
        Week 20
    86.3 (81.6 to 91)
    88.9 (84.9 to 92.9)
    92.1 (88.4 to 95.8)
        Week 24
    84.9 (80 to 89.8)
    84.7 (80.1 to 89.3)
    90.1 (86 to 94.2)
        Follow-up Week 24
    81.5 (76.1 to 86.8)
    81.3 (76.3 to 86.3)
    90.6 (86.6 to 94.6)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Extended Rapid Virologic Response (eRVR)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Extended Rapid Virologic Response (eRVR) [11]
    End point description
    eRVR was defined as hepatitis C virus RNA levels to be <lower limit of quantitation i.e., 25 IU/mL target not detected at both Week 4 and Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. The analysis was performed on all treated subjects who received at least 1 dose of study therapy.
    End point type
    Secondary
    End point timeframe
    Week 4 and Week 12
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to evaluate for the specified arm only.
    End point values
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Number of subjects analysed
    205
    235
    203
    Units: Percentage of Subjects
        number (confidence interval 95%)
    68.3 (61.9 to 74.7)
    63.4 (57.2 to 69.6)
    80.3 (74.8 to 85.8)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From start of study treatment up to 7 days post last dose of study treatment
    Adverse event reporting additional description
    On-treatment
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Prior Null or partial responder: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, null or partial responder to peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.

    Reporting group title
    Intolerant or Ineligible: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Subjects with Hepatitis C virus genotype 1b, intolerant to or ineligible for peginterferon alfa and ribavirin received daclatasvir 60 mg orally once daily and asunaprevir 100 mg orally twice daily for up to 24 weeks.

    Reporting group title
    Treatment-naive: Asunaprevir+ Daclatasvir
    Reporting group description
    		 Treatment-naive subjects with Hepatitis C virus genotype 1b received daclatasvir 60 mg orally once daily, and asunaprevir 100 mg twice daily for up to 24 weeks.

    Serious adverse events
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 205 (5.37%)
    16 / 235 (6.81%)
    12 / 205 (5.85%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatocellular carcinoma
         subjects affected / exposed
    3 / 205 (1.46%)
    3 / 235 (1.28%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic neoplasm
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Liver Transplant
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Colitis
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac Chest pain
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchiectasis
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial Fibrillation
         subjects affected / exposed
    0 / 205 (0.00%)
    2 / 235 (0.85%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Glaucoma
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess intestinal
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 235 (0.00%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute tonsillitis
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 235 (0.43%)
    0 / 205 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 205 (0.00%)
    0 / 235 (0.00%)
    1 / 205 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Prior Null or partial responder: Asunaprevir+ Daclatasvir Intolerant or Ineligible: Asunaprevir+ Daclatasvir Treatment-naive: Asunaprevir+ Daclatasvir
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    167 / 205 (81.46%)
    203 / 235 (86.38%)
    172 / 205 (83.90%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    12 / 205 (5.85%)
    9 / 235 (3.83%)
    7 / 205 (3.41%)
         occurrences all number
    14
    11
    7
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    19 / 205 (9.27%)
    19 / 235 (8.09%)
    14 / 205 (6.83%)
         occurrences all number
    21
    20
    15
    Headache
         subjects affected / exposed
    50 / 205 (24.39%)
    59 / 235 (25.11%)
    50 / 205 (24.39%)
         occurrences all number
    76
    74
    62
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    12 / 205 (5.85%)
    26 / 235 (11.06%)
    4 / 205 (1.95%)
         occurrences all number
    12
    27
    4
    Fatigue
         subjects affected / exposed
    45 / 205 (21.95%)
    52 / 235 (22.13%)
    43 / 205 (20.98%)
         occurrences all number
    46
    59
    46
    Influenza like illness
         subjects affected / exposed
    7 / 205 (3.41%)
    5 / 235 (2.13%)
    11 / 205 (5.37%)
         occurrences all number
    8
    5
    12
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    8 / 205 (3.90%)
    18 / 235 (7.66%)
    8 / 205 (3.90%)
         occurrences all number
    8
    23
    8
    Abdominal pain upper
         subjects affected / exposed
    10 / 205 (4.88%)
    18 / 235 (7.66%)
    16 / 205 (7.80%)
         occurrences all number
    10
    20
    16
    Constipation
         subjects affected / exposed
    20 / 205 (9.76%)
    17 / 235 (7.23%)
    10 / 205 (4.88%)
         occurrences all number
    23
    17
    11
    Diarrhoea
         subjects affected / exposed
    27 / 205 (13.17%)
    47 / 235 (20.00%)
    24 / 205 (11.71%)
         occurrences all number
    34
    56
    30
    Dyspepsia
         subjects affected / exposed
    8 / 205 (3.90%)
    14 / 235 (5.96%)
    8 / 205 (3.90%)
         occurrences all number
    9
    14
    10
    Nausea
         subjects affected / exposed
    22 / 205 (10.73%)
    28 / 235 (11.91%)
    25 / 205 (12.20%)
         occurrences all number
    27
    29
    30
    Vomiting
         subjects affected / exposed
    8 / 205 (3.90%)
    7 / 235 (2.98%)
    11 / 205 (5.37%)
         occurrences all number
    9
    7
    12
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    18 / 205 (8.78%)
    21 / 235 (8.94%)
    14 / 205 (6.83%)
         occurrences all number
    18
    21
    14
    Oropharyngeal pain
         subjects affected / exposed
    7 / 205 (3.41%)
    2 / 235 (0.85%)
    12 / 205 (5.85%)
         occurrences all number
    8
    3
    12
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    8 / 205 (3.90%)
    12 / 235 (5.11%)
    11 / 205 (5.37%)
         occurrences all number
    8
    12
    11
    Pruritus
         subjects affected / exposed
    14 / 205 (6.83%)
    18 / 235 (7.66%)
    8 / 205 (3.90%)
         occurrences all number
    15
    18
    8
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    20 / 205 (9.76%)
    9 / 235 (3.83%)
    16 / 205 (7.80%)
         occurrences all number
    20
    10
    19
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    17 / 205 (8.29%)
    15 / 235 (6.38%)
    10 / 205 (4.88%)
         occurrences all number
    17
    15
    10
    Myalgia
         subjects affected / exposed
    7 / 205 (3.41%)
    22 / 235 (9.36%)
    13 / 205 (6.34%)
         occurrences all number
    7
    23
    14
    Back pain
         subjects affected / exposed
    8 / 205 (3.90%)
    11 / 235 (4.68%)
    11 / 205 (5.37%)
         occurrences all number
    8
    11
    11
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    16 / 205 (7.80%)
    13 / 235 (5.53%)
    18 / 205 (8.78%)
         occurrences all number
    19
    14
    18
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 205 (6.34%)
    17 / 235 (7.23%)
    16 / 205 (7.80%)
         occurrences all number
    14
    19
    16

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Jun 2012
    Updated the protocol with new safety information and added guidance regarding the management of subjects treated with daclatasvir/asunaprevir with unexplained pyrexia. Hemophilia was added as an exclusion criteria.
    21 Aug 2012
    Added the collection of cortisol in urine at Day 1, Week 12, and Week 24. Modified the research hypothesis by adding a well-defined criterion for the success of daclatasvir/asunaprevir therapy in the treatment-naive cohort. Separated the primary objective into 1 objective for prior null or partial responders to pegylated-interferon and a second for treatment-naive subjects, in accordance with the modification to the research hypothesis.
    14 Jun 2013
    Added description of available data for subjects who have received rescue therapy with QUAD (ASV/DCV/pegIFN-alpha/RBV) rescue therapy. Added option for subjects to continue rescue therapy with QUAD for 48 weeks. Revised contraception guidance for women of childbearing potential (WOCBP) and male subjects sexually active with WOCBP.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 01 13:16:14 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA