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 double-blind, placebo-controlled, randomised trial to prove the therapeutic concept and to determine the safety, tolerability and pharmacokinetic profile of EMA401 (angiotensin II type 2 receptor antagonist) administered orally in patients with postherpetic neuralgia

    Summary
    EudraCT number
    		 2011-000977-29
    Trial protocol
    		 CZ   BG  
    Global end of trial date
    11 Jul 2012

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Jun 2016
    First version publication date
    12 Jun 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EMA401-003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    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 AG, +41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, +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
    11 Jul 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Jul 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the efficacy of EMA401 when administered orally, twice daily (100 mg b.i.d.), in patients with postherpetic neuralgia, as assessed by difference in mean pain intensity score compared to placebo.
    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
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Aug 2011
    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
    Bulgaria: 41
    Country: Number of subjects enrolled
    Czech Republic: 9
    Country: Number of subjects enrolled
    Georgia: 14
    Country: Number of subjects enrolled
    Serbia: 7
    Country: Number of subjects enrolled
    Ukraine: 68
    Country: Number of subjects enrolled
    South Africa: 44
    Worldwide total number of subjects
    183
    EEA total number of subjects
    50
    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)
    81
    From 65 to 84 years
    97
    85 years and over
    5

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Eligibility for the study was determined by Screening tests and fulfilment of eligibility criteria including assessment of pain. Seven consecutive days of pain assessment was required during the 14 day Screening Period.

    Period 1
    Period 1 title
    Treatment plus Follow-up Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 EMA401 100 mg BID
    Arm description
    		 Two EMA401 50 mg capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of 100 mg on the morning of Day 29. Followed by a follow-up period until day 42.
    Arm type
    		 Experimental

    Investigational medicinal product name
    EMA401
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Two EMA401 50 mg capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of 100 mg on the morning of Day 29.

    Arm title
    		 Placebo BID
    Arm description
    		 Two placebo capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of placebo on the morning of Day 29. Followed by a follow-up period until day 42.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Two placebo capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of placebo on the morning of Day 29.

    Number of subjects in period 1
    		EMA401 100 mg BID Placebo BID
    Started
    92
    91
    Completed
    86
    83
    Not completed
    6
    8
         Consent withdrawn during follow-up
    1
    1
         Adverse event, non-fatal
    1
    3
         Consent withdrawn during treatment period
    4
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    EMA401 100 mg BID
    Reporting group description
    		 Two EMA401 50 mg capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of 100 mg on the morning of Day 29. Followed by a follow-up period until day 42.

    Reporting group title
    Placebo BID
    Reporting group description
    		 Two placebo capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of placebo on the morning of Day 29. Followed by a follow-up period until day 42.

    Reporting group values
    		 EMA401 100 mg BID Placebo BID Total
    Number of subjects
    		 92 91 183
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 40 41 81
        From 65-84 years
    		 50 47 97
        85 years and over
    		 2 3 5
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.5 ( 14.9 ) 63.4 ( 14.4 ) -
    Gender categorical
    Units: Subjects
        Female
    		 49 51 100
        Male
    		 43 40 83

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    EMA401 100 mg BID
    Reporting group description
    		 Two EMA401 50 mg capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of 100 mg on the morning of Day 29. Followed by a follow-up period until day 42.

    Reporting group title
    Placebo BID
    Reporting group description
    		 Two placebo capsules twice daily (morning and evening), at least 1 hour before a meal, for 28 days, and a single dose of placebo on the morning of Day 29. Followed by a follow-up period until day 42.

    Primary: Change from Baseline in Mean Pain Intensity Score at Week 4

    		 Close Top of page
    End point title
    		 Change from Baseline in Mean Pain Intensity Score at Week 4
    End point description
    The daily pain intensity score was assessed using the 11-Point Numerical Rating Scale/Likert Scale (NRS). Every evening, patients evaluated their average pain during the past 24 hours by circling the appropriate corresponding number between 0 (“no pain”) and 10 (“pain as bad as you can imagine”). LOCF= last observation carried forward
    End point type
    Primary
    End point timeframe
    Baseline and Week 4
    End point values
    		 EMA401 100 mg BID Placebo BID
    Number of subjects analysed
    92 [1]
    91 [2]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Baseline
    6.306 ( 1.024 )
    6.325 ( 1.086 )
        Week 4
    4.017 ( 2.054 )
    4.724 ( 1.896 )
        Change from Baseline at Week 4
    -2.289 ( 1.753 )
    -1.601 ( 1.661 )
    Notes
    [1] - Change from Baseline at Week 4 N's are based on LOCF imputation method for missing data.
    [2] - Change from Baseline at Week 4 N's are based on LOCF imputation method for missing data.
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    EMA401 100 mg BID v Placebo BID
    Number of subjects included in analysis
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0066 [3]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.6922
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1888
         upper limit
    		 -0.1957
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2516
    Notes
    [3] - p-value for treatment group comparison was based on ANCOVA with baseline mean of pain intensity score, treatment, age and gender as covariates.

    Secondary: Change from Baseline in Mean Pain Intesity Score at Weeks 1, 2 and 3

    		 Close Top of page
    End point title
    		 Change from Baseline in Mean Pain Intesity Score at Weeks 1, 2 and 3
    End point description
    The daily pain intensity score was assessed using the 11-Point Numerical Rating Scale/Likert Scale (NRS). Every evening, patients evaluated their average pain during the past 24 hours by circling the appropriate corresponding number between 0 (“no pain”) and 10 (“pain as bad as you can imagine”).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 2 and 3
    End point values
    		 EMA401 100 mg BID Placebo BID
    Number of subjects analysed
    92 [4]
    91 [5]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Change from Baseline at Week 1
    -0.675 ( 0.927 )
    -0.546 ( 1.096 )
        Change from Baseline at Week 2
    -1.272 ( 1.165 )
    -1.037 ( 1.398 )
        Change from Baseline at Week 3
    -1.786 ( 1.461 )
    -1.254 ( 1.553 )
    Notes
    [4] - Based on LOCF imputation method for missing data.
    [5] - Based on LOCF imputation method for missing data.
    Statistical analysis title
    		 Statistical Analysis - Week 1
    Comparison groups
    EMA401 100 mg BID v Placebo BID
    Number of subjects included in analysis
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4153 [6]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.1228
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4197
         upper limit
    		 0.174
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1504
    Notes
    [6] - p-value for treatment group comparison was based on ANCOVA with baseline mean of pain intensity score, treatment, age and gender as covariates.
    Statistical analysis title
    		 Statistical Analysis - Week 2
    Comparison groups
    EMA401 100 mg BID v Placebo BID
    Number of subjects included in analysis
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2217 [7]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.234
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6105
         upper limit
    		 0.1425
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1908
    Notes
    [7] - p-value for treatment group comparison was based on ANCOVA with baseline mean of pain intensity score, treatment, age and gender as covariates.
    Statistical analysis title
    		 Statistical Analysis - Week 3
    Comparison groups
    EMA401 100 mg BID v Placebo BID
    Number of subjects included in analysis
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0188 [8]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.5264
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9645
         upper limit
    		 -0.0883
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.222
    Notes
    [8] - p-value for treatment group comparison was based on ANCOVA with baseline mean of pain intensity score, treatment, age and gender as covariates.

    Secondary: Percentage of Participants Achieving a ≥ 30% Decrease in Mean Pain Intensity Score from Baseline to Week 4

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving a ≥ 30% Decrease in Mean Pain Intensity Score from Baseline to Week 4
    End point description
    The daily pain intensity score was assessed using the 11-Point Numerical Rating Scale/Likert Scale (NRS). Every evening, patients evaluated their average pain during the past 24 hours by circling the appropriate corresponding number between 0 (“no pain”) and 10 (“pain as bad as you can imagine”). Participants with available Week 4 data were classified as responders when the mean pain intensity score was at least 30% lower than it was at Baseline.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 EMA401 100 mg BID Placebo BID
    Number of subjects analysed
    92
    91
    Units: percentage of participants
        number (not applicable)
    56.5
    34.1
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    EMA401 100 mg BID v Placebo BID
    Number of subjects included in analysis
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0024 [9]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.392
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.214
         upper limit
    		 0.719
    Notes
    [9] - p-value for treatment group comparison was based on logistic regression model including baseline mean pain intensity score, treatment, age and gender as covariates.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Serious Adverse Events are monitored from date of First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All other adverse events are monitored from First Patient First Treatment until Last Patient Last Visit.
    Adverse event reporting additional description
    Treatment Emergent Serious Adverse Events (SAEs) for the Safety Set.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    EMA401 100 mg BID
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 EMA401 100 mg BID Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 92 (1.09%)
    2 / 91 (2.20%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Polyuria
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 EMA401 100 mg BID Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 92 (17.39%)
    9 / 91 (9.89%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 92 (6.52%)
    2 / 91 (2.20%)
         occurrences all number
    6
    2
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 92 (1.09%)
    3 / 91 (3.30%)
         occurrences all number
    1
    3
    Nausea
         subjects affected / exposed
    3 / 92 (3.26%)
    3 / 91 (3.30%)
         occurrences all number
    3
    3
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    3 / 92 (3.26%)
    1 / 91 (1.10%)
         occurrences all number
    3
    1
    Infections and infestations
    Pharyngitis
         subjects affected / exposed
    3 / 92 (3.26%)
    0 / 91 (0.00%)
         occurrences all number
    3
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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-Sat May 04 18:27:27 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA