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   43871   clinical trials with a EudraCT protocol, of which   7290   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 multicenter, open-label, randomized, 3-arm, phase II profiling trial of pharmacokinetics, pharmacodynamics and safety of DEB025/Alisporivir in combination with ribavirin therapy in chronic hepatitis C genotype 2 and 3 treatment naïve patients

    Summary
    EudraCT number
    		 2012-004185-17
    Trial protocol
    		 SE   DE   GB   PL  
    Global end of trial date
    24 Mar 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Apr 2016
    First version publication date
    14 Apr 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CDEB025A2222
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01970904
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma GmbH, +41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma GmbH, +41 613241111,
    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
    24 Mar 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Mar 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective was to explore pharmacodynamic (i.e. HCV viral load), pharmacokinetic, and safety profiles between three treatment groups receiving different doses of alisporivir in combination with RBV during the first 12 weeks treatment in chronic hepatitis C GT 2 and 3 treatment naïve patients.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 ribavirin 1000 - 1200 mg/day was given as backbone therapy in all 3 arms together with doses of alisporivir
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Oct 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 61
    Country: Number of subjects enrolled
    United Kingdom: 23
    Country: Number of subjects enrolled
    Poland: 28
    Country: Number of subjects enrolled
    Sweden: 35
    Worldwide total number of subjects
    147
    EEA total number of subjects
    147
    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)
    144
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 147treatment naïve chronic hepatitis C GT2/3 patients randomized into one of the three treatment groups in a 1:1:1 ratio Randomization was stratified by the viral load at screening (≥ 800,000 IU/mL [5.903 log10] or < 800,000 IU/mL [5.903 log10])

    Period 1
    Period 1 title
    Treatment Period (12 or 24 weeks) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Alisporivir (DEB025) 200mg + Ribavirin
    Arm description
    		 Alisporivir (200 mg twice daily, BID): one capsule (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the response at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Alisporivir
    Investigational medicinal product code
    DEB025
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    100 or 200 mg soft gel capsules by mouth

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The daily scheduled dose was 1000 mg/day orally for patients < 75 kg or 1200 mg/day for ≥ 75 kg of body weight at screening.

    Arm title
    		 Alisporivir (DEB025) 300mg + Ribavirin
    Arm description
    		 Alisporivir (300 mg BID): one capsule of 200 mg and one capsule of 100 mg or three capsules (100 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The daily scheduled dose was 1000 mg/day orally for patients < 75 kg or 1200 mg/day for ≥ 75 kg of body weight at screening.

    Investigational medicinal product name
    Alisporivir
    Investigational medicinal product code
    DEB025
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    100 or 200 mg soft gel capsules by mouth

    Arm title
    		 Alisporivir (DEB025) 400mg + Ribavirin
    Arm description
    		 Alisporivir (400 mg BID): two capsules (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Alisporivir
    Investigational medicinal product code
    DEB025
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    100 or 200 mg soft gel capsules by mouth

    Investigational medicinal product name
    Ribavirin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The daily scheduled dose was 1000 mg/day orally for patients < 75 kg or 1200 mg/day for ≥ 75 kg of body weight at screening.

    Number of subjects in period 1
    		Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Started
    48
    50
    49
    Completed at week 12
    4 [1]
    4 [2]
    6 [3]
    Completed at week 24
    19 [4]
    28 [5]
    21 [6]
    Completed
    23
    32
    27
    Not completed
    25
    18
    22
         Adverse event, non-fatal
    4
    2
    6
         Non-compliance with study treatment
    1
    1
    2
         Patient/guardian decision
    -
    2
    3
         Lack of efficacy
    20
    13
    11
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone data are based on week 12 and week 24 where as completed is all patients (week 12 and week 24) who completed the treatment.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone data are based on week 12 and week 24 where as completed is all patients (week 12 and week 24) who completed the treatment.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone data are based on week 12 and week 24 where as completed is all patients (week 12 and week 24) who completed the treatment.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone data are based on week 12 and week 24 where as completed is all patients (week 12 and week 24) who completed the treatment.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone data are based on week 12 and week 24 where as completed is all patients (week 12 and week 24) who completed the treatment.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone data are based on week 12 and week 24 where as completed is all patients (week 12 and week 24) who completed the treatment.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Alisporivir (DEB025) 200mg + Ribavirin
    Reporting group description
    		 Alisporivir (200 mg twice daily, BID): one capsule (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the response at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.

    Reporting group title
    Alisporivir (DEB025) 300mg + Ribavirin
    Reporting group description
    		 Alisporivir (300 mg BID): one capsule of 200 mg and one capsule of 100 mg or three capsules (100 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.

    Reporting group title
    Alisporivir (DEB025) 400mg + Ribavirin
    Reporting group description
    		 Alisporivir (400 mg BID): two capsules (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.

    Reporting group values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin Total
    Number of subjects
    		 48 50 49 147
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 47 50 47 144
        From 65-84 years
    		 1 0 2 3
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 45.3 ± 10.11 41.4 ± 10.86 41.7 ± 11.8 -
    Gender categorical
    Units: Subjects
        Female
    		 17 20 23 60
        Male
    		 31 30 26 87

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Alisporivir (DEB025) 200mg + Ribavirin
    Reporting group description
    		 Alisporivir (200 mg twice daily, BID): one capsule (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the response at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.

    Reporting group title
    Alisporivir (DEB025) 300mg + Ribavirin
    Reporting group description
    		 Alisporivir (300 mg BID): one capsule of 200 mg and one capsule of 100 mg or three capsules (100 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.

    Reporting group title
    Alisporivir (DEB025) 400mg + Ribavirin
    Reporting group description
    		 Alisporivir (400 mg BID): two capsules (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results. There was a 24 week post treatment follow up period during which patients did not receive any study medication.

    Primary: Change in log transformed Hepatitis C virus (HCV) Ribonucleic acid (RNA) from baseline through Week 12

    		 Close Top of page
    End point title
    		 Change in log transformed Hepatitis C virus (HCV) Ribonucleic acid (RNA) from baseline through Week 12 [1]
    End point description
    Viral load was analyzed as continuous variables using data in log10 IU/mL units as reported by the central laboratory. Baseline is defined as the last non-missing value before first administration of study drug. At week 12 only patients with a value at both baseline and week 12 were included.
    End point type
    Primary
    End point timeframe
    Baseline, 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: There was no statistical hypothesis testing planned for this primary endpoint
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    42
    44
    44
    Units: log10 IU/mL
        arithmetic mean (standard deviation)
    -3.586 ± 1.9833
    -4.173 ± 2.0039
    -4.131 ± 1.8248
    No statistical analyses for this end point

    Secondary: Number of patients with Sustained Virologic Response at Week 12 follow up (SVR12)

    		 Close Top of page
    End point title
    		 Number of patients with Sustained Virologic Response at Week 12 follow up (SVR12)
    End point description
    SVR12 is sustained virologic response at week 12 follow up: HCV RNA undetectable (by < LLOQ) 12 weeks after end of treatment. LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL. Definition Non-responder: Failure to achieve undetectable serum HCV RNA during treatment Definition Null non-responder: Failure to achieve a decrease in serum HCV RNA concentration ≥ 2 log10 from baseline to treatment week 12 Definition Partial Non-responder: HCV RNA decrease ≥ 2 log10 from baseline to treatment week 12 but never undetectable during treatment
    End point type
    Secondary
    End point timeframe
    12 weeks after end of treatment ( total 24 weeks or 36 weeks from baseline)
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
        SVR12
    18
    27
    25
        Non-Responder
    23
    12
    7
        Null non-responder
    10
    6
    2
        Partial non-responder
    13
    6
    5
    No statistical analyses for this end point

    Secondary: Number of patients with rapid virologic response (RVR) after 4 weeks of treatment

    		 Close Top of page
    End point title
    		 Number of patients with rapid virologic response (RVR) after 4 weeks of treatment
    End point description
    Rapid Virologic Response by LLOQ is defined as serum HCV RNA < LLOQ after 4 weeks of treatment where LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL.
    End point type
    Secondary
    End point timeframe
    Baseline to week 4
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    8
    11
    16
    No statistical analyses for this end point

    Secondary: Number of patients with extremely rapid virologic response (eRVR) after 2 weeks of treatment

    		 Close Top of page
    End point title
    		 Number of patients with extremely rapid virologic response (eRVR) after 2 weeks of treatment
    End point description
    Extremely Rapid Virologic Response by LLOQ (eRVR) , also known as very Rapid Virologic Response by LLOQ (vRVR) is defined as serum HCV RNA < LLOQ after 2 weeks of treatment where LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL.
    End point type
    Secondary
    End point timeframe
    Baseline to week 2
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    3
    5
    7
    No statistical analyses for this end point

    Secondary: Number of patients with early virologic response (EVR) and complete early virologic response (cEVR) after 12 weeks of treatment

    		 Close Top of page
    End point title
    		 Number of patients with early virologic response (EVR) and complete early virologic response (cEVR) after 12 weeks of treatment
    End point description
    Early virologic response (EVR) is defined as HCV RNA decrease ≥ 2 log10 or HCV RNA < LLOQ after 12 weeks of treatment and complete early viral response (cEVR) is defined as serum HCV RNA < LLOQ after 12 weeks of treatment where LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL.
    End point type
    Secondary
    End point timeframe
    Baseline to week 12
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
        EVR
    33
    37
    38
        cEVR
    22
    30
    33
    No statistical analyses for this end point

    Secondary: Number of patients with end of treatment response

    		 Close Top of page
    End point title
    		 Number of patients with end of treatment response
    End point description
    End of treatment response is defined as HCV RNA undetectable (by < LLOQ) at treatment end (completed or prematurely discontinued) where LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL.
    End point type
    Secondary
    End point timeframe
    Baseline to End of treatment (12 weeks or 24 weeks)
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    22
    35
    34
    No statistical analyses for this end point

    Secondary: NUmber of patients with sustained virologic response 4 weeks after end of treatment

    		 Close Top of page
    End point title
    		 NUmber of patients with sustained virologic response 4 weeks after end of treatment
    End point description
    Sustained virologic response at Week 4 follow up (SVR4) is defined as HCV RNA undetectable (by <LLOQ) 4 weeks after end of treatment where LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL.
    End point type
    Secondary
    End point timeframe
    4 weeks after end of treatment (total 16 weeks or 28 weeks from baseline)
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    19
    32
    29
    No statistical analyses for this end point

    Secondary: Number of patients with sustained virologic response 24 weeks after end of treatment

    		 Close Top of page
    End point title
    		 Number of patients with sustained virologic response 24 weeks after end of treatment
    End point description
    Sustained virologic response at Week 24 follow up (SVR24) is defined as HCV RNA undetectable (by < LLOQ) 24 weeks after end of treatment where LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL.
    End point type
    Secondary
    End point timeframe
    24 weeks after end of treatment (total 36 weeks or 48 weeks from baseline)
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    17
    26
    25
    No statistical analyses for this end point

    Secondary: Number of patients with confirmed viral breakthrough during treatment

    		 Close Top of page
    End point title
    		 Number of patients with confirmed viral breakthrough during treatment
    End point description
    Viral breakthrough is defined as confirmed (by a separate blood draw): increase of HCV RNA by >= 1 log10 above nadir (where nadir is the lowest HCV RNA level during treatment) and HCV RNA >= 100 IU/mL (2 log10) while still on treatment), or HCV RNA >= 100 IU/mL (2 log10) after previously being undetectable while still on treatment.
    End point type
    Secondary
    End point timeframe
    12 weeks or 24 weeks
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    16
    14
    14
    No statistical analyses for this end point

    Secondary: Number of patients with relapse (based on primary and secondary definition)

    		 Close Top of page
    End point title
    		 Number of patients with relapse (based on primary and secondary definition)
    End point description
    Primary definition of relapse : Patients with non-missing and positive follow-up HCV RNA > LLOQ results after imputation are considered as relapsers, if they fully completed assigned treatments and were End of treatment (ETR) responders. Secondary definition odf relapse: patients with any positive follow-up HCV RNA > LLOQ results (after imputation) or no follow-up HCV RNA assessments (at all) are considered as relapsers if they fully completed assigned treatments and were ETR responders. LLOQ (Lower limit of Quantification) is defined as HCV RNA < 15 IU/mL.
    End point type
    Secondary
    End point timeframe
    12 weeks or 24 weeks of treatment
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
        Primary Definition of Relapse
    5
    8
    8
        Secondary Definition of Relapse
    5
    9
    9
    No statistical analyses for this end point

    Secondary: Number of patients with normalized alanine aminotransferase (ALT) at end of treatment

    		 Close Top of page
    End point title
    		 Number of patients with normalized alanine aminotransferase (ALT) at end of treatment
    End point description
    ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of clinical liver recovery. Abnormal ALT is defined as an ALT value ≥ ULN. Patients with abnormal ALT at baseline but normalized at end of treatment were reported in this endpoint.
    End point type
    Secondary
    End point timeframe
    After 12 weeks or 24 weeks of treatment
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    30
    35
    35
    No statistical analyses for this end point

    Secondary: Number of patients with normalized alanine aminotransferase (ALT) at end of study

    		 Close Top of page
    End point title
    		 Number of patients with normalized alanine aminotransferase (ALT) at end of study
    End point description
    ALT levels were assessed as part of clinical chemistry assessments throughout the study as a measure of clinical liver recovery. Abnormal ALT is defined as an ALT value >= ULN. Patients with abnormal ALT at baseline and normalized ALT at end of study are reported in this endpoint.
    End point type
    Secondary
    End point timeframe
    36 to 48 weeks including post treatment follow up
    End point values
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin
    Number of subjects analysed
    48
    50
    49
    Units: Patients
    15
    23
    24
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Alisporivir (DEB025) 200mg + Ribavirin
    Reporting group description
    		 Alisporivir (200 mg twice daily, BID): one capsule (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the response at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results.

    Reporting group title
    Alisporivir (DEB025) 400mg + Ribavirin
    Reporting group description
    		 Alisporivir (400 mg BID): two capsules (200 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results.

    Reporting group title
    Alisporivir (DEB025) 300mg + Ribavirin
    Reporting group description
    		 Alisporivir (300 mg BID): one capsule of 200 mg and one capsule of 100 mg or three capsules (100 mg) BID for 12 or 24 weeks depending on the response at Week 2, and Ribavirin: 1000 mg/day or 1200 mg/day orally (depending on weight) in two divided doses for 12 or 24 weeks depending on the responses at Week 2, respectively. The treatment was for 12 or 24 weeks based on Week 2 Hepatitis C virus (HCV) ribonucleic acid (RNA) results.

    Serious adverse events
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 48 (8.33%)
    4 / 49 (8.16%)
    1 / 49 (2.04%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    CHEMICAL PERITONITIS
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 49 (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
    RADIUS FRACTURE
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 49 (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
    Nervous system disorders
    HYPERAESTHESIA
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 49 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOAESTHESIA
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 49 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 49 (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
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (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
    HAEMATEMESIS
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (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
    Hepatobiliary disorders
    GALLBLADDER PERFORATION
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (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
    INSOMNIA
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 49 (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
    Renal and urinary disorders
    RENAL IMPAIRMENT
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (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
    ARTHRALGIA
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 49 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JOINT SWELLING
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 49 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    SEPSIS
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (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
    UROSEPSIS
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (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
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 49 (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
    		 Alisporivir (DEB025) 200mg + Ribavirin Alisporivir (DEB025) 400mg + Ribavirin Alisporivir (DEB025) 300mg + Ribavirin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    41 / 48 (85.42%)
    41 / 49 (83.67%)
    41 / 49 (83.67%)
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    3 / 48 (6.25%)
    13 / 49 (26.53%)
    8 / 49 (16.33%)
         occurrences all number
    3
    15
    10
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    3 / 48 (6.25%)
    6 / 49 (12.24%)
    3 / 49 (6.12%)
         occurrences all number
    3
    6
    3
    FATIGUE
         subjects affected / exposed
    21 / 48 (43.75%)
    22 / 49 (44.90%)
    18 / 49 (36.73%)
         occurrences all number
    21
    26
    18
    FEELING COLD
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 49 (6.12%)
    0 / 49 (0.00%)
         occurrences all number
    1
    3
    0
    MUCOSAL DRYNESS
         subjects affected / exposed
    0 / 48 (0.00%)
    3 / 49 (6.12%)
    1 / 49 (2.04%)
         occurrences all number
    0
    3
    1
    PYREXIA
         subjects affected / exposed
    3 / 48 (6.25%)
    3 / 49 (6.12%)
    5 / 49 (10.20%)
         occurrences all number
    4
    3
    5
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    3 / 48 (6.25%)
    7 / 49 (14.29%)
    5 / 49 (10.20%)
         occurrences all number
    3
    7
    6
    DYSPNOEA
         subjects affected / exposed
    2 / 48 (4.17%)
    9 / 49 (18.37%)
    3 / 49 (6.12%)
         occurrences all number
    2
    9
    3
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    1 / 48 (2.08%)
    1 / 49 (2.04%)
    4 / 49 (8.16%)
         occurrences all number
    1
    1
    5
    Psychiatric disorders
    DEPRESSED MOOD
         subjects affected / exposed
    1 / 48 (2.08%)
    5 / 49 (10.20%)
    3 / 49 (6.12%)
         occurrences all number
    1
    5
    3
    DEPRESSION
         subjects affected / exposed
    4 / 48 (8.33%)
    3 / 49 (6.12%)
    4 / 49 (8.16%)
         occurrences all number
    4
    3
    4
    INSOMNIA
         subjects affected / exposed
    7 / 48 (14.58%)
    7 / 49 (14.29%)
    6 / 49 (12.24%)
         occurrences all number
    8
    7
    6
    SLEEP DISORDER
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 49 (4.08%)
    3 / 49 (6.12%)
         occurrences all number
    3
    2
    3
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    4 / 48 (8.33%)
    5 / 49 (10.20%)
    1 / 49 (2.04%)
         occurrences all number
    4
    5
    1
    DYSGEUSIA
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 49 (6.12%)
    2 / 49 (4.08%)
         occurrences all number
    2
    3
    2
    HEADACHE
         subjects affected / exposed
    22 / 48 (45.83%)
    22 / 49 (44.90%)
    22 / 49 (44.90%)
         occurrences all number
    27
    27
    24
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    5 / 48 (10.42%)
    7 / 49 (14.29%)
    4 / 49 (8.16%)
         occurrences all number
    5
    9
    4
    Ear and labyrinth disorders
    VERTIGO
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 49 (6.12%)
    1 / 49 (2.04%)
         occurrences all number
    2
    3
    1
    Eye disorders
    OCULAR ICTERUS
         subjects affected / exposed
    0 / 48 (0.00%)
    4 / 49 (8.16%)
    1 / 49 (2.04%)
         occurrences all number
    0
    4
    1
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    5 / 48 (10.42%)
    2 / 49 (4.08%)
    4 / 49 (8.16%)
         occurrences all number
    5
    2
    4
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    2 / 48 (4.17%)
    6 / 49 (12.24%)
    6 / 49 (12.24%)
         occurrences all number
    2
    7
    7
    DIARRHOEA
         subjects affected / exposed
    6 / 48 (12.50%)
    4 / 49 (8.16%)
    9 / 49 (18.37%)
         occurrences all number
    6
    4
    9
    DYSPEPSIA
         subjects affected / exposed
    4 / 48 (8.33%)
    3 / 49 (6.12%)
    3 / 49 (6.12%)
         occurrences all number
    4
    3
    3
    MOUTH ULCERATION
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 49 (6.12%)
    0 / 49 (0.00%)
         occurrences all number
    2
    3
    0
    NAUSEA
         subjects affected / exposed
    13 / 48 (27.08%)
    16 / 49 (32.65%)
    10 / 49 (20.41%)
         occurrences all number
    16
    20
    12
    VOMITING
         subjects affected / exposed
    7 / 48 (14.58%)
    2 / 49 (4.08%)
    3 / 49 (6.12%)
         occurrences all number
    9
    3
    5
    Hepatobiliary disorders
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 49 (6.12%)
    2 / 49 (4.08%)
         occurrences all number
    2
    4
    3
    JAUNDICE
         subjects affected / exposed
    4 / 48 (8.33%)
    3 / 49 (6.12%)
    1 / 49 (2.04%)
         occurrences all number
    5
    3
    1
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 49 (6.12%)
    1 / 49 (2.04%)
         occurrences all number
    2
    3
    1
    PRURITUS
         subjects affected / exposed
    7 / 48 (14.58%)
    4 / 49 (8.16%)
    7 / 49 (14.29%)
         occurrences all number
    8
    4
    7
    DRY SKIN
         subjects affected / exposed
    5 / 48 (10.42%)
    5 / 49 (10.20%)
    9 / 49 (18.37%)
         occurrences all number
    5
    5
    10
    RASH
         subjects affected / exposed
    2 / 48 (4.17%)
    6 / 49 (12.24%)
    3 / 49 (6.12%)
         occurrences all number
    2
    6
    3
    Endocrine disorders
    HYPOTHYROIDISM
         subjects affected / exposed
    3 / 48 (6.25%)
    1 / 49 (2.04%)
    0 / 49 (0.00%)
         occurrences all number
    3
    1
    0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    4 / 48 (8.33%)
    2 / 49 (4.08%)
    4 / 49 (8.16%)
         occurrences all number
    4
    2
    4
    ARTHRALGIA
         subjects affected / exposed
    2 / 48 (4.17%)
    2 / 49 (4.08%)
    5 / 49 (10.20%)
         occurrences all number
    2
    2
    5
    MUSCLE SPASMS
         subjects affected / exposed
    1 / 48 (2.08%)
    1 / 49 (2.04%)
    3 / 49 (6.12%)
         occurrences all number
    1
    1
    3
    Infections and infestations
    NASOPHARYNGITIS
         subjects affected / exposed
    6 / 48 (12.50%)
    6 / 49 (12.24%)
    9 / 49 (18.37%)
         occurrences all number
    6
    7
    9
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    3 / 48 (6.25%)
    4 / 49 (8.16%)
    2 / 49 (4.08%)
         occurrences all number
    3
    4
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Oct 2013
    - The definition of “Partial Early Virologic Response” was removed from “ Definition of Virologic Response Parameters” table, and definition of viral breakthrough was amended for clarity. A typographical error in the definition of eRVR was corrected throughout the protocol - One Inclusion , 2 Exclusion criterion were amended for clarification. An abdominal ultrasound assessment was added to the screening visit table and eligibility assessment - The hypertensive criteria was clarified in the “hypertension management” and vital sign assessment for consistency. - The significant ALT elevation criterion was amended for consistency.

    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.
    After a portfolio review, and in light of the advancement of several successful oral anti-HCV agents, Novartis decided to no longer focus on HCV development. This decision was not in any way affected or influenced by new safety data for alisporivir.
    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-Sun May 05 09:55:14 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA