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   43845   clinical trials with a EudraCT protocol, of which   7282   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Symptomatic Ulcerative Colitis Patients with Moderate to Severe Disease Activity

    Summary
    EudraCT number
    		 2016-000390-20
    Trial protocol
    		 GB   HU   LV   PL   LT   BG   CZ  
    Global end of trial date
    31 Oct 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Aug 2018
    First version publication date
    10 Aug 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    TOP1288-TV-02
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02888379
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Topivert Pharma Limited
    Sponsor organisation address
    52 Princes Gate, London, United Kingdom, SW7 2PG
    Public contact
    Head of Clinical Development , TOPIVERT Pharma Limited, +44 203763 9469, Mike.Taylor@topivert.com
    Scientific contact
    Head of Clinical Development , TOPIVERT Pharma Limited, +44 203763 9469, Mike.Taylor@topivert.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
    31 Oct 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Oct 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to assess the effect of TOP1288 200 mg Rectal Solution on endoscopic remission, as indicated by the Mayo Clinic modified endoscopic subscore, after 4 consecutive weeks of once daily bedtime treatment
    Protection of trial subjects
    Safety assessments were performed during the screening period (after informed consent was obtained) and the double-blind treatment period (at Day 1 [prior to and following dosing], Day 7 [±2 days], and Week 4 [±2 days]). Following Week 4, there was a 1-week follow-up period for collection of AE information, including outcome of previously reported unresolved AEs. The safety of the IMP was assessed via collection of AEs (including any clinically significant untoward histological findings), vital signs measurements, and clinical laboratory test results (hematology, clinical chemistry, and urinalysis). The investigator was to elicit information regarding the occurrence of AEs through open-ended questioning of the subject, a physical examination, and by review of laboratory test results. Any clinically significant untoward histological finding from a colon biopsy (compared to the baseline findings) was to be recorded as an AE. Progression of disease was recorded as an AE. Significant medication errors/misuse was captured as an AE. Each reported AE was evaluated for seriousness, severity, causal relationship to the IMP, duration, action taken, and outcome, all of which were recorded in the eCRF.
    Background therapy
    		 The majority of subjects (and all subjects in the Czech Republic) received standard of care background treatment with a stable dose of oral 5-ASA (at doses ≤4.8 g/day). Oral corticosteroids were also permitted (prednisolone, at doses ≤30 mg/day or budesonide ≤9 mg/day).
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Sep 2016
    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
    Poland: 14
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Czech Republic: 4
    Country: Number of subjects enrolled
    Hungary: 8
    Country: Number of subjects enrolled
    Latvia: 12
    Country: Number of subjects enrolled
    Lithuania: 4
    Country: Number of subjects enrolled
    Ukraine: 32
    Worldwide total number of subjects
    77
    EEA total number of subjects
    45
    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)
    71
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Study Period was 08 September 2016 (first subject screened) – 28 June 2017 (last subject completed). A total of 31 sites in 7 countries (Czech Republic, Hungary, Latvia, Lithuania, Poland, Ukraine and United Kingdom) screened at least 1 subject in the study.

    Pre-assignment
    Screening details
    		 A total of 60 to 80 subjects were planned to be enrolled/randomized to TOP1288 200 mg Rectal Solution or matching Placebo Rectal Solution in a 2:1 ratio: 138 subjects were screened, and 77 subjects were randomized.

    Period 1
    Period 1 title
    Intent-to-treat (ITT)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The bottles containing TOP1288 200 mg Rectal Solution and matching Placebo Rectal Solution were yellow and identical in appearance, with the IMP masked. Both treatments were identical with respect to packaging, volume administered, viscosity, and the applicator used. The process for breaking the blind was handled through the IWRS. Investigators were not to break the blind unless there was a subject safety issue that required immediate unblinding for proper management of the subject.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ITT Experimental
    Arm description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    TOP1288
    Investigational medicinal product code
    TOP1288
    Other name
    Pharmaceutical forms
    Rectal solution
    Routes of administration
    Rectal use
    Dosage and administration details
    A dose of 200 mg TOP1288 was given once daily in 100ml of the Rectal Solution.

    Arm title
    		 ITT Placebo
    Arm description
    		 Placebo Rectal Solution Once Daily for 4 Weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Rectal solution
    Routes of administration
    Rectal use
    Dosage and administration details
    A 100 ml dose of the rectal solution was given once daily.

    Number of subjects in period 1
    		ITT Experimental ITT Placebo
    Started
    51
    26
    Completed
    45
    21
    Not completed
    6
    5
         Consent withdrawn by subject
    3
    -
         Adverse event, non-fatal
    3
    2
         Lack of efficacy
    -
    3
    Period 2
    Period 2 title
    modified intent-to-treat (mITT)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The bottles containing TOP1288 200 mg Rectal Solution and matching Placebo Rectal Solution were yellow and identical in appearance, with the IMP masked. Both treatments were identical with respect to packaging, volume administered, viscosity, and the applicator used. The process for breaking the blind was handled through the IWRS. Investigators were not to break the blind unless there was a subject safety issue that required immediate unblinding for proper management of the subject.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 mITT Experimental
    Arm description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    TOP1288
    Investigational medicinal product code
    TOP1288
    Other name
    Pharmaceutical forms
    Rectal solution
    Routes of administration
    Rectal use
    Dosage and administration details
    A dose of 200 mg TOP1288 was given once daily in 100ml of the Rectal Solution.

    Arm title
    		 mITT Placebo
    Arm description
    		 Placebo Rectal Solution Once Daily for 4 Weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Rectal solution
    Routes of administration
    Rectal use
    Dosage and administration details
    A 100 ml dose of the rectal solution was given once daily.

    Number of subjects in period 2
    		mITT Experimental mITT Placebo
    Started
    45
    21
    Completed
    41
    20
    Not completed
    4
    1
         No Week 4 Endoscopy
    4
    1
    Period 3
    Period 3 title
    Per Protocol (PP)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The bottles containing TOP1288 200 mg Rectal Solution and matching Placebo Rectal Solution were yellow and identical in appearance, with the IMP masked. Both treatments were identical with respect to packaging, volume administered, viscosity, and the applicator used. The process for breaking the blind was handled through the IWRS. Investigators were not to break the blind unless there was a subject safety issue that required immediate unblinding for proper management of the subject.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PP Experimental
    Arm description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    TOP1288
    Investigational medicinal product code
    TOP1288
    Other name
    Pharmaceutical forms
    Rectal solution
    Routes of administration
    Rectal use
    Dosage and administration details
    A dose of 200 mg TOP1288 was given once daily in 100ml of the Rectal Solution.

    Arm title
    		 PP Placebo
    Arm description
    		 Placebo Rectal Solution Once Daily for 4 Weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Rectal solution
    Routes of administration
    Rectal use
    Dosage and administration details
    A 100 ml dose of the rectal solution was given once daily.

    Number of subjects in period 3
    		PP Experimental PP Placebo
    Started
    41
    20
    Completed
    37
    17
    Not completed
    4
    3
         Protocol deviation
    4
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ITT Experimental
    Reporting group description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks

    Reporting group title
    ITT Placebo
    Reporting group description
    		 Placebo Rectal Solution Once Daily for 4 Weeks

    Reporting group values
    		 ITT Experimental ITT Placebo Total
    Number of subjects
    		 51 26 77
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 48 23 71
        From 65-84 years
    		 3 3 6
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 42.6 ± 13.12 42.3 ± 14.16 -
    Gender categorical
    Units: Subjects
        Female
    		 22 12 34
        Male
    		 29 14 43
    Concomitant Steroid use
    ‘Concomitant’ medications are medications which start at any time prior to randomization, and ongoing at the time of randomization, or which start at any time after randomization up until the subject’s post treatment follow up visit.
    Units: Subjects
        Yes
    		 13 6 19
        No
    		 38 20 58
    Concomitant immunomodulator use
    ‘Concomitant’ medications are medications which start at any time prior to randomization, and ongoing at the time of randomization, or which start at any time after randomization up until the subject’s post treatment follow up visit.
    Units: Subjects
        Yes
    		 6 3 9
        No
    		 45 23 68
    Concomitant 5-ASA use
    ‘Concomitant’ medications are medications which start at any time prior to randomization, and ongoing at the time of randomization, or which start at any time after randomization up until the subject’s post treatment follow up visit.
    Units: Subjects
        Yes
    		 51 24 75
        No
    		 0 2 2
    Prior biologic use
    ‘Prior’ medications are medications which started and stopped prior to randomization.
    Units: Subjects
        Yes
    		 1 1 2
        No
    		 50 25 75
    Smoking Status
    Units: Subjects
        Current
    		 3 0 3
        Former
    		 7 4 11
        Never
    		 41 22 63
    MES
    Mayo Clinic modified endoscopic subscore
    Units: arbitrary
        arithmetic mean (standard deviation)
    		 2.3 ± 0.48 2.4 ± 0.50 -
    Partial Mayo Clinic Score
    Partial Mayo Clinic Score is the sum of endoscopic, rectal bleeding, and stool frequency subscores
    Units: arbitrary
        arithmetic mean (standard deviation)
    		 6.1 ± 1.17 6.3 ± 1.28 -
    Duration of UC
    Units: Years
        arithmetic mean (standard deviation)
    		 7.3 ± 6.80 5.3 ± 4.55 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ITT Experimental
    Reporting group description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks

    Reporting group title
    ITT Placebo
    Reporting group description
    		 Placebo Rectal Solution Once Daily for 4 Weeks
    Reporting group title
    mITT Experimental
    Reporting group description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks

    Reporting group title
    mITT Placebo
    Reporting group description
    		 Placebo Rectal Solution Once Daily for 4 Weeks
    Reporting group title
    PP Experimental
    Reporting group description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks

    Reporting group title
    PP Placebo
    Reporting group description
    		 Placebo Rectal Solution Once Daily for 4 Weeks

    Primary: Endoscopic remission

    		 Close Top of page
    End point title
    		 Endoscopic remission
    End point description
    Proportion of Subjects Achieving Endoscopic Remission (MES of 0 or 1) at Week 4 (Day 29±2). Endoscopic remission is defined as a Mayo Clinic modified endoscopy subscore of 0 (indicating normal or inactive disease) or 1 (mild disease).
    End point type
    Primary
    End point timeframe
    The primary efficacy endpoint is proportion of subjects achieving endoscopic remission at Visit 3 (Week 4 [Day 29±2])
    End point values
    		 ITT Experimental ITT Placebo mITT Experimental mITT Placebo PP Experimental PP Placebo
    Number of subjects analysed
    51
    26
    41
    20
    37
    17
    Units: Number of subjects achieving remission
    14
    13
    14
    13
    14
    11
    Statistical analysis title
    		 Percentage difference between TOP1288 and Placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    ITT Experimental v ITT Placebo
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [1]
    P-value
    		 = 0.986 [2]
    Method
    		 Fisher exact
    Parameter type
    		 Difference of means
    Point estimate
    -23
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -41.68
         upper limit
    		 -3.42
    Notes
    [1] - Difference in percentage responder rate between experimental and placebo groups.
    [2] - 1-sided p-value, testing TOP1288 remission proportion greater than placebo remission proportion, was calculated from Fisher’s exact test
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    mITT Experimental v mITT Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [3]
    P-value
    		 = 0.995 [4]
    Method
    		 Fisher exact
    Parameter type
    		 Difference of means
    Point estimate
    -31
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -52.21
         upper limit
    		 -9.49
    Notes
    [3] - Difference in percentage responder rate between experimental and placebo groups.
    [4] - 1-sided p-value, testing TOP1288 remission proportion greater than placebo remission proportion, was calculated from Fisher’s exact test
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    PP Experimental v PP Placebo
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [5]
    P-value
    		 = 0.984 [6]
    Method
    		 Fisher exact
    Parameter type
    		 Difference of means
    Point estimate
    -27
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -50.01
         upper limit
    		 -3.73
    Notes
    [5] - Difference in percentage responder rate between experimental and placebo groups.
    [6] - 1-sided p-value, testing TOP1288 remission proportion greater than placebo remission proportion, was calculated from Fisher’s exact test

    Secondary: Change from baseline to Week 4 in UCEIS Score

    		 Close Top of page
    End point title
    		 Change from baseline to Week 4 in UCEIS Score
    End point description
    Following sigmoidoscopy, the central reader also graded the endoscopic findings using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scale, which provided a composite score for vascular pattern, bleeding, and erosions and ulcers for the most severe lesions observed during endoscopic examination. The assessment was completed at screening visit (baseline) and visit 3 (Week 4). For quantitative measurements, change from baseline to week 4 was calculated as [Value at Week 4 Visit – Baseline Value].
    End point type
    Secondary
    End point timeframe
    The secondary efficacy objectives assessed the effect of 4 weeks of treatment with TOP1288 200 mg Rectal Solution compared with Placebo Rectal Solution on the change from baseline to Week 4
    End point values
    		 ITT Experimental ITT Placebo mITT Experimental mITT Placebo PP Experimental PP Placebo
    Number of subjects analysed
    51
    26
    41
    20
    37
    17
    Units: UCEIS Score
        arithmetic mean (standard deviation)
    -0.67 ± 1.681
    -1.35 ± 1.810
    -0.83 ± 1.843
    -1.75 ± 1.888
    -1.00 ± 1.841
    -1.82 ± 2.007
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 4 in Partial Mayo Clinic Score

    		 Close Top of page
    End point title
    		 Change from baseline to Week 4 in Partial Mayo Clinic Score
    End point description
    The Partial Mayo Clinic Score is the sum of the endoscopic, rectal bleeding, and stool frequency subscores of the Mayo Clinic Score scale. The Physician’s Global Assessment subscale was not included in the Partial Mayo Clinic Score. Scoring ranged between 0 and 3 for each of the parameters. The assessment was completed at screening visit (baseline) and visit 3 (Week 4). For quantitative measurements, change from baseline to week 4 was calculated as [Value at Week 4 visit – Baseline Value].
    End point type
    Secondary
    End point timeframe
    The secondary efficacy objectives assessed the effect of 4 weeks of treatment with TOP1288 200 mg Rectal Solution compared with Placebo Rectal Solution on the change from baseline to Week 4
    End point values
    		 ITT Experimental ITT Placebo mITT Experimental mITT Placebo PP Experimental PP Placebo
    Number of subjects analysed
    51
    26
    41
    20
    37
    17
    Units: Change Partial Mayo Clinic Score
        arithmetic mean (standard deviation)
    -1.78 ± 2.194
    -2.54 ± 2.284
    -2.22 ± 2.242
    -3.30 ± 2.055
    -2.43 ± 2.167
    -3.35 ± 2.149
    No statistical analyses for this end point

    Secondary: Endoscopic healing

    		 Close Top of page
    End point title
    		 Endoscopic healing
    End point description
    Endoscopic healing is defined as Mayo Clinic modified endoscopic (MES) subscore of 0. Mayo Clinic modified endoscopic subscore were assessed at visit 3 (Week 4).
    End point type
    Secondary
    End point timeframe
    Number of subjects achieving endoscopic remission at Visit 3 (Week 4 [Day 29±2])
    End point values
    		 ITT Experimental ITT Placebo mITT Experimental mITT Placebo PP Experimental PP Placebo
    Number of subjects analysed
    51
    26
    41
    20
    37
    17
    Units: Number of subjects
    7
    6
    7
    6
    7
    6
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    ITT Experimental v ITT Placebo
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.344
    Method
    		 Fisher exact
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.06
         upper limit
    		 9.36
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    mITT Experimental v mITT Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.321
    Method
    		 Fisher exact
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.03
         upper limit
    		 10.18
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    PP Experimental v PP Placebo
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.303
    Method
    		 Fisher exact
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.31
         upper limit
    		 9.56

    Secondary: Rectal Bleeding

    		 Close Top of page
    End point title
    		 Rectal Bleeding
    End point description
    Proportion of subject with an improvement (reduction) in Mayo Clinic rectal bleeding, change from baseline to visit 3 (Week 4) in mayo clinic rectal bleeding subscore was calculated. Subjects observed with ≥1 improvement (reduction) in change from baseline to visit 3 (Week 4) in mayo clinical rectal bleeding was considered as a responder (i.e. proportion of subjects with an improvement in Mayo Clinic rectal bleeding). Screening visit was considered as baseline for this endpoint.
    End point type
    Secondary
    End point timeframe
    Number of subjects achieving improvement in Mayo Clinic Rectal Bleeding Subscore of ≥1 at Visit 3 (Week 4 [Day 29±2])
    End point values
    		 ITT Experimental ITT Placebo mITT Experimental mITT Placebo PP Experimental PP Placebo
    Number of subjects analysed
    51
    26
    41
    20
    37
    17
    Units: Number of subjects
    31
    15
    28
    15
    26
    13
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    ITT Experimental v ITT Placebo
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.794
    Method
    		 Chi-squared
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.1
         upper limit
    		 26.29
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    mITT Experimental v mITT Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.59
    Method
    		 Chi-squared
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.39
         upper limit
    		 16.97
    Statistical analysis title
    		 Percentage difference between TOP1288 and placebo
    Statistical analysis description
    Difference in percentage responder rate between experimental (TOP1288) and placebo groups.
    Comparison groups
    PP Experimental v PP Placebo
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.751
    Method
    		 Chi-squared
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.12
         upper limit
    		 18.72

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Safety assessments were performed during the screening period and the double-blind treatment period. Following Week 4, there was a 1-week follow-up period for collection of AE information, including outcome of previously reported unresolved AEs.
    Adverse event reporting additional description
    Each reported AE was evaluated for seriousness, severity, causal relationship to the IMP, duration, action taken, and outcome, all of which were recorded in the eCRF.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Safety Experimental
    Reporting group description
    		 TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks

    Reporting group title
    Safety Placebo
    Reporting group description
    		 Placebo Rectal Solution Once Daily for 4 Weeks

    Serious adverse events
    		 Safety Experimental Safety Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 26 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Safety Experimental Safety Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 51 (54.90%)
    12 / 26 (46.15%)
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    2 / 51 (3.92%)
    1 / 26 (3.85%)
         occurrences all number
    2
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Faecal calprotectin increased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Lymphocyte count increased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Monocyte count decreased
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Procedural pain
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Thermal burn
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Burning sensation
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Dysgeusia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Frequent bowel movements
         subjects affected / exposed
    7 / 51 (13.73%)
    5 / 26 (19.23%)
         occurrences all number
    7
    6
    Colitis ulcerative
         subjects affected / exposed
    6 / 51 (11.76%)
    3 / 26 (11.54%)
         occurrences all number
    6
    3
    Abdominal pain
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    Nausea
         subjects affected / exposed
    2 / 51 (3.92%)
    1 / 26 (3.85%)
         occurrences all number
    2
    1
    Colitis
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Flatulence
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal sounds abnormal
         subjects affected / exposed
    0 / 51 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Abdominal discomfort
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Abdominal distension
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Gastrointestinal motility disorder
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Nervousness
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Hypophosphataemia
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hypernatraemia
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Nov 2016
    - New QuintilesIMS Medical Monitor was assigned to the study, and a second study drug manufacturer and supplier is being used for the study. - Number of subjects to be randomised was increased from 60 to a range of approximately 60 to 80. - Following Sponsor approval, the intensive PK blood sampling at Visit 1 may be an optional assessment if the Investigator considers it to be a significant barrier to an individual subject’s participation in the study. - Requirement that all patients in the Czech Republic must be receiving a stable oral dose of 5-aminosalicylic acid therapy (up to 4.8 g/day) for at least 2 weeks before Screening, and they must be willing to continue on the regimen for the duration of the study. - Subjects will be advised to remain supine for approximately (not “at least”) 1 hour after receiving their first dose of study medication on Day 1. - Patients who test positive for Blastocystis hominis may be eligible for the study based on the judgement of the Investigator. - Haemoglobin range lowered from <10.5 to <8.5 g/dL. Absolute neutrophil count lowered from <1.5 x 109/L to <1.0 x 109/L. - The phrase “or 5 half-lives, whichever is longer” was added in regard to prohibition of the use of the biologic agents, including vedolizumab, for 3 months prior to Screening. - Rescreening allowed once in subjects with a single isolated test result outside the specific range considered clinically significant. - The instructions to subjects to limit their mobility for at least 1 hour following administration and to remain supine, if possible, was removed. - Week 1 assessment of TOP1288 plasma concentrations was added. - Follow-up on unresolved AEs will continue until resolution or until the end of the study (last patient last visit), whichever occurs first.
    27 Mar 2017
    - Correction of the 24-hour medical contact to be consistent with all other clinical trial documentation. - Data obtained from subjects enrolled in this study was classified and analysed using four analysis populations (ITT, mITT, PP and Safety). The primary analysis will be based on the Intent-to-Treat (ITT) population. The analysis will be repeated using the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. Descriptive statistics will be used to summarise all secondary efficacy endpoints, including individual item scores by visit and treatment group, based on the ITT, mITT and PP populations. Clarification that subject demographic characteristics will be summarised for all of the analysis populations. - Clarification that ‘no imputation’ refers to the primary efficacy endpoint and that other imputation techniques for missing efficacy data will be described in the Statistical Analysis Plan as several key secondary endpoints are not responder-based.

    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.
    The high response rate seen for all endpoints in the placebo arm confounds assessment for efficacy and hinders the drawing of any firm conclusions. Statistical analysis was conducted for all endpoints, where the system allows input, data is included.
    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-Fri Apr 19 05:57:17 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA