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    Clinical Trial Results:
    A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects with Chronic HCV GT1, GT4, and GT6 Infection.

    Summary
    EudraCT number
    2014-000137-22
    Trial protocol
    CZ   SE   DE  
    Global end of trial date
    06 Sep 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    11 Sep 2016
    First version publication date
    11 Sep 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MK-5172-060
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02105467
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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
    06 Sep 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Sep 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This was an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) in treatment-naïve participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection. Participants were randomly assigned (3:1 ratio) to immediate treatment or deferred treatment (placebo control).
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    05 Jun 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 17
    Country: Number of subjects enrolled
    Czech Republic: 28
    Country: Number of subjects enrolled
    France: 35
    Country: Number of subjects enrolled
    Germany: 34
    Country: Number of subjects enrolled
    Korea, Republic of: 31
    Country: Number of subjects enrolled
    Sweden: 24
    Country: Number of subjects enrolled
    Taiwan: 25
    Country: Number of subjects enrolled
    United States: 205
    Country: Number of subjects enrolled
    Israel: 22
    Worldwide total number of subjects
    421
    EEA total number of subjects
    121
    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)
    374
    From 65 to 84 years
    47
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    For Subject Disposition, Period 1 covers Day 1 through Week 12 for both treatment groups. Period 2 covers Week 12 through Week 36 for the Immediate Treatment Group (ITG) and Week 12 through Week 28 for the Deferred Treatment Group (DTG). Period 3 covers Week 28 through Week 52 for the DTG; the ITG completed the study with Period 2.

    Pre-assignment
    Screening details
    A total of 469 participants were screened and 421 were randomized.

    Period 1
    Period 1 title
    Period 1
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Immediate Treatment Group
    Arm description
    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks (Period 1), followed by a 24-week follow-up period (Period 2)
    Arm type
    Experimental

    Investigational medicinal product name
    grazoprevir 100 mg / elbasvir 50 mg FDC
    Investigational medicinal product code
    Other name
    MK-5172A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet once daily by mouth for 12 weeks beginning on Day 1 (Period 1)

    Arm title
    Deferred Treatment Group
    Arm description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Blinded placebo tablet once daily by mouth for 12 weeks beginning on Day 1 (Period 1)

    Number of subjects in period 1
    Immediate Treatment Group Deferred Treatment Group
    Started
    316
    105
    Completed
    314
    105
    Not completed
    2
    0
         Death
    1
    -
         Lost to follow-up
    1
    -
    Period 2
    Period 2 title
    Period 2
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Immediate Treatment Group
    Arm description
    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks (Period 1) followed by a 24-week follow-up period (Period 2).
    Arm type
    Experimental

    Investigational medicinal product name
    grazoprevir 100 mg / elbasvir 50 mg FDC
    Investigational medicinal product code
    Other name
    MK-5172A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet once daily by mouth for 12 weeks beginning on Day 1 (Period 1). No study drug was administered during Period 2.

    Arm title
    Deferred Treatment Group
    Arm description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Blinded placebo tablet once daily by mouth for 12 weeks beginning on Day 1 (Period 1)

    Investigational medicinal product name
    grazoprevir 100 mg / elbasvir 50 mg FDC
    Investigational medicinal product code
    Other name
    MK-5172A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Open-label grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet once daily by mouth for 12 weeks beginning at Week 16 (Period 2)

    Number of subjects in period 2 [1]
    Immediate Treatment Group Deferred Treatment Group
    Started
    314
    104
    Completed
    312
    102
    Not completed
    2
    2
         Death
    1
    -
         Consent withdrawn by subject
    -
    2
         Lost to follow-up
    1
    -
    Notes
    [1] - 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: One participant proceeded directly to Period 3
    Period 3
    Period 3 title
    Period 3
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Deferred Treatment Group
    Arm description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Blinded placebo tablet once daily by mouth for 12 weeks beginning on Day 1 (Period 1)

    Investigational medicinal product name
    grazoprevir 100 mg / elbasvir 50 mg FDC
    Investigational medicinal product code
    Other name
    MK-5172A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Open-label grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet once daily by mouth for 12 weeks beginning at Week 16 (Period 2). No study drug was administered during Period 3.

    Number of subjects in period 3 [2]
    Deferred Treatment Group
    Started
    103
    Completed
    102
    Not completed
    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: One participant proceeded directly to Period 3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Immediate Treatment Group
    Reporting group description
    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks (Period 1), followed by a 24-week follow-up period (Period 2)

    Reporting group title
    Deferred Treatment Group
    Reporting group description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).

    Reporting group values
    Immediate Treatment Group Deferred Treatment Group Total
    Number of subjects
    316 105 421
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    287 87 374
        From 65-84 years
    29 18 47
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    52.2 ± 11.1 53.8 ± 11.2 -
    Gender Categorical
    Units: Subjects
        Female
    145 49 194
        Male
    171 56 227
    HCV Genotype
    HCV genotype was determined for each participant at Screening
    Units: Subjects
        Genotype 1a
    157 54 211
        Genotype 1b
    131 40 171
        Genotype 4
    18 8 26
        Genotype 6
    10 3 13

    End points

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    End points reporting groups
    Reporting group title
    Immediate Treatment Group
    Reporting group description
    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks (Period 1), followed by a 24-week follow-up period (Period 2)

    Reporting group title
    Deferred Treatment Group
    Reporting group description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).
    Reporting group title
    Immediate Treatment Group
    Reporting group description
    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination (FDC) tablet orally once daily for 12 weeks (Period 1) followed by a 24-week follow-up period (Period 2).

    Reporting group title
    Deferred Treatment Group
    Reporting group description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).
    Reporting group title
    Deferred Treatment Group
    Reporting group description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).

    Subject analysis set title
    Deferred Treatment Group (Blinded Treatment Period 1)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).

    Subject analysis set title
    Deferred Treatment Group (Open-label Treatment Period 2)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received blinded placebo tablet orally once daily for 12 weeks (Period 1), followed by a 4-week unblinding/washout period and 12 weeks of open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily (Period 2), followed by a 24-week follow-up period (Period 3).

    Primary: Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)

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    End point title
    Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12) [1] [2]
    End point description
    Hepatitis C virus ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR12 was defined as HCV RNA <Lower Limit of Quantification (<15 IU/mL) 12 weeks after the end of all study therapy. The Full Analysis Set included randomized participants who received at least one dose of study treatment. This endpoint applied only to the Immediate Treatment group.
    End point type
    Primary
    End point timeframe
    Week 24 (12 weeks after the end of treatment)
    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: No statistical analysis was conducted for this endpoint comparing treatment groups in the study
    [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: This endpoint applied only to the Immediate Treatment group
    End point values
    Immediate Treatment Group
    Number of subjects analysed
    316
    Units: Percentage of participants
        number (confidence interval 95%)
    94.6 (91.5 to 96.8)
    No statistical analyses for this end point

    Primary: Percentage of Participants Experiencing at Least One Adverse Event

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    End point title
    Percentage of Participants Experiencing at Least One Adverse Event
    End point description
    An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign(including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an adverse event. The All Subjects as Treated population included randomized participants who received at least one dose of study treatment. This endpoint applied only to the blinded treatment period.
    End point type
    Primary
    End point timeframe
    Up to Week 14 (14 days after blinded treatment was completed)
    End point values
    Immediate Treatment Group Deferred Treatment Group
    Number of subjects analysed
    316
    105
    Units: Percentage of participants
        number (not applicable)
    67.4
    68.6
    Statistical analysis title
    Difference in Percentage of Participants
    Statistical analysis description
    Between-treatment difference (Immediate Treatment Group - Deferred Treatment Group) was analyzed using the Miettinen and Nurminen method.
    Comparison groups
    Immediate Treatment Group v Deferred Treatment Group
    Number of subjects included in analysis
    421
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Risk difference (RD)
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.8
         upper limit
    9.6

    Primary: Percentage of Participants Discontinued from Study Treatment Because of an Adverse Event

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    End point title
    Percentage of Participants Discontinued from Study Treatment Because of an Adverse Event
    End point description
    An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an adverse event. The All Subjects as Treated population included randomized participants who received at least one dose of study treatment. This endpoint applied only to the blinded treatment period.
    End point type
    Primary
    End point timeframe
    Up to Week 12 (end of blinded treatment)
    End point values
    Immediate Treatment Group Deferred Treatment Group
    Number of subjects analysed
    316
    105
    Units: Percentage of participants
        number (not applicable)
    0.9
    1
    Statistical analysis title
    Difference in Percentage of Participants
    Statistical analysis description
    Between-treatment difference (Immediate Treatment Group - Deferred Treatment Group) was analyzed using the Miettinen and Nurminen method.
    Comparison groups
    Immediate Treatment Group v Deferred Treatment Group
    Number of subjects included in analysis
    421
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Risk difference (RD)
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.4
         upper limit
    2

    Secondary: Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24)

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    End point title
    Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24) [3]
    End point description
    Hepatitis C virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR24 was defined as HCV RNA <Lower Limit of Quantification (<15 IU/mL) 24 weeks after the end of all study therapy. The Full Analysis Set included randomized participants who received at least one dose of study treatment. This endpoint applied only to the Immediate Treatment group.
    End point type
    Secondary
    End point timeframe
    Week 36 (24 weeks after the end of treatment)
    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: This endpoint applied only to the Immediate Treatment group
    End point values
    Immediate Treatment Group
    Number of subjects analysed
    316
    Units: Percentage of participants
        number (confidence interval 95%)
    94.3 (91.1 to 96.6)
    No statistical analyses for this end point

    Other pre-specified: Percentage of Participants Achieving Sustained Virologic Response at 4 Weeks After the End of Treatment (SVR4)

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    End point title
    Percentage of Participants Achieving Sustained Virologic Response at 4 Weeks After the End of Treatment (SVR4) [4]
    End point description
    Hepatitis C virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR4 was defined as HCV RNA <Lower Limit of Quantification (<15 IU/mL) 4 weeks after the end of all study therapy. The Full Analysis Set included randomized participants who received at least one dose of study treatment. This endpoint applied only to the Immediate Treatment group.
    End point type
    Other pre-specified
    End point timeframe
    Week 16 (4 weeks after the end of 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: This endpoint applied only to the Immediate Treatment group
    End point values
    Immediate Treatment Group
    Number of subjects analysed
    316
    Units: Percentage of participants
        number (confidence interval 95%)
    97.2 (94.7 to 98.7)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Immediate Treatment Group: Up to Week 36; Deferred Treatment Group (Blinded Treatment): Up to Week 16; Deferred Treatment Group (Open-label Treatment): Week 16 to Week 52
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.0, 18.0
    Reporting groups
    Reporting group title
    Immediate Treatment Group
    Reporting group description
    Participants received blinded grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks.

    Reporting group title
    Deferred Treatment Group (Blinded Treatment)
    Reporting group description
    Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks. Time frame for AE assessment was up to 36 weeks for one participant who did not receive open-label treatment but remained in follow-up.

    Reporting group title
    Deferred Treatment Group (Open-label Treatment)
    Reporting group description
    Participants received blinded placebo tablet orally once daily for 12 weeks; after a 4-week unblinding/washout period participants received open label grazoprevir 100 mg / elbasvir 50 mg FDC tablet orally once daily for 12 weeks. Follow-up was for an additional 24 weeks.

    Serious adverse events
    Immediate Treatment Group Deferred Treatment Group (Blinded Treatment) Deferred Treatment Group (Open-label Treatment)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    15 / 316 (4.75%)
    4 / 105 (3.81%)
    3 / 103 (2.91%)
         number of deaths (all causes)
    2
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Multiple fractures
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma pancreas
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Bladder cancer
         subjects affected / exposed
    0 / 316 (0.00%)
    0 / 105 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Prostate cancer
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Acute myocardial infarction
         subjects affected / exposed
    0 / 316 (0.00%)
    0 / 105 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 105 (0.95%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Eye disorders
    Retinal haemorrhage
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 105 (0.95%)
    0 / 103 (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
    Asthenia
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Chest pain
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Ear and labyrinth disorders
    Meniere's disease
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Hiatus hernia strangulated
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Osteoarthritis
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 105 (0.95%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 105 (0.95%)
    0 / 103 (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
    Infections and infestations
    Peritoneal abscess
         subjects affected / exposed
    0 / 316 (0.00%)
    0 / 105 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 105 (0.00%)
    0 / 103 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Immediate Treatment Group Deferred Treatment Group (Blinded Treatment) Deferred Treatment Group (Open-label Treatment)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    147 / 316 (46.52%)
    60 / 105 (57.14%)
    42 / 103 (40.78%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    51 / 316 (16.14%)
    18 / 105 (17.14%)
    17 / 103 (16.50%)
         occurrences all number
    61
    19
    19
    Dizziness
         subjects affected / exposed
    9 / 316 (2.85%)
    7 / 105 (6.67%)
    0 / 103 (0.00%)
         occurrences all number
    9
    9
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    49 / 316 (15.51%)
    18 / 105 (17.14%)
    12 / 103 (11.65%)
         occurrences all number
    53
    19
    13
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 316 (1.90%)
    6 / 105 (5.71%)
    3 / 103 (2.91%)
         occurrences all number
    6
    6
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    14 / 316 (4.43%)
    7 / 105 (6.67%)
    5 / 103 (4.85%)
         occurrences all number
    15
    7
    5
    Nausea
         subjects affected / exposed
    29 / 316 (9.18%)
    8 / 105 (7.62%)
    8 / 103 (7.77%)
         occurrences all number
    32
    8
    8
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    7 / 316 (2.22%)
    8 / 105 (7.62%)
    1 / 103 (0.97%)
         occurrences all number
    7
    9
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    20 / 316 (6.33%)
    6 / 105 (5.71%)
    3 / 103 (2.91%)
         occurrences all number
    22
    6
    3
    Back pain
         subjects affected / exposed
    10 / 316 (3.16%)
    3 / 105 (2.86%)
    7 / 103 (6.80%)
         occurrences all number
    10
    3
    7
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    20 / 316 (6.33%)
    7 / 105 (6.67%)
    7 / 103 (6.80%)
         occurrences all number
    23
    8
    8
    Upper respiratory tract infection
         subjects affected / exposed
    17 / 316 (5.38%)
    2 / 105 (1.90%)
    5 / 103 (4.85%)
         occurrences all number
    18
    2
    6

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Jun 2014
    The primary reason for Protocol Amendment 1 was to add urinalysis assessments.
    25 Sep 2014
    The primary reason for Protocol Amendment 2 was to make participants infected with HCV GT5 no longer eligible for enrollment.

    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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