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   43873   clinical trials with a EudraCT protocol, of which   7293   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:
    Double-blind, randomised, placebo-controlled, multi-centre phase III clinical study on the efficacy and tolerability of budesonide capsules versus placebo for maintenance of remission in patients with collagenous colitis

    Summary
    EudraCT number
    		 2007-001315-31
    Trial protocol
    		 SE   DE   HU   DK   CZ   BE  
    Global end of trial date
    16 Sep 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Aug 2016
    First version publication date
    12 Aug 2016
    Other versions
    Summary report(s)
    		 Gut - Open access paper

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BUC-63/COC
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01278082
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Dr Falk Pharma GmbH
    Sponsor organisation address
    Leinenweberstrasse 5, Freiburg, Germany, 79108
    Public contact
    Department of Medical Science, Dr Falk Pharma GmbH, +49 761-1514-0,
    Scientific contact
    Department of Medical Science, Dr Falk Pharma GmbH, +49 761-1514-0,
    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
    15 Oct 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Mar 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Sep 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To prove the superiority of budesonide compared to placebo as maintenance therapy in keeping patients with collagenous colitis in remission over a one-year period.
    Protection of trial subjects
    Prior to recruitment of patients, all relevant documents of the clinical study were submitted and approved by the Independent Ethics Committees (IECs) responsible for the participating investigators. Written consent documents embodied the elements of informed consent as described in the Declaration of Helsinki, the ICH Guidelines for Good Clinical Practice (GCP) and were in accordance with all applicable laws and regulations. The informed consent form and patient information sheet described the planned and permitted uses, transfers and disclosures of the patient’s personal data and personal health information for purposes of conducting the study. The informed consent form and the patient information sheet further explained the nature of the study, its objectives and potential risks and benefits as well as the date informed consent was given. Before being enrolled in the clinical trial, every patient was informed that participation in this trial was voluntary and that he/she could withdraw from the study at any time without giving a reason and without having to fear any loss in his/her medical care. The patient’s consent was obtained in writing before the start of the study. By signing the informed consent, the patient declared that he/she was participating voluntarily and intended to follow the study protocol instructions and the instructions of the investigator and to answer the questions asked during the course of the trial. For colonoscopy and biopsy sampling to be performed for confirmation of diagnosis of collagenous colitis by the central pathologist, the patients received the standard preparation for bowel cleansing and sedation during the colonoscopy as routinely performed at the study sites.
    Background therapy
    		 No concomitant background therapy was allowed during the trial.
    Evidence for comparator
    		 Using a placebo arm in this clinical trial as reference was ethically justified and in accordance with Article 29 of the Declaration of Helsinki (2008), as there were compelling and scientifically sound methodological reasons for the use of a placebo control in this trial, since there were no comparator products with a marketing authorization for the maintenance treatment of collagenous colitis available.
    Actual start date of recruitment
    18 Apr 2008
    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
    Sweden: 73
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Czech Republic: 4
    Country: Number of subjects enrolled
    Denmark: 4
    Country: Number of subjects enrolled
    Germany: 10
    Worldwide total number of subjects
    92
    EEA total number of subjects
    92
    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)
    64
    From 65 to 84 years
    28
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This clinical trial was conducted in 22 sites in 5 countries: 1 centre in Belgium, 3 centres in the Czech Republic, 2 centres in Denmark, 4 centres in Germany, and 12 centres in Sweden. First patient was screened (entered) at the 18 Apr 2008. Last patient completed his last visit at 16 Sept 2013.

    Pre-assignment
    Screening details
    		 110 patients with active collagenous colitis were enrolled for open-labeled (OL) induction of clinical remission treatment with budesonide. 92 Patients in clinical remission at the end of OL treatment were randomized to a 1-year double-blind maintenance of remission treatment with budesonide or placebo.

    Pre-assignment period milestones
    Number of subjects started
    		 110 [1]
    Number of subjects completed
    		 92

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Protocol deviation: 9
    Reason: Number of subjects
    		 Not matching InC/ExC: 9
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 110 patients were enrolled into the open-label induction period; of these 92 fulfill the inclusion criteria for period 1 (double-blind maintenance phase).
    Period 1
    Period 1 title
    Double-blind maintenance of remission (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
    Blinding implementation details
    The appearance and size of the placebo capsules was indistinguishable from the budesonide capsules.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Budesonide DB Maintenance
    Arm description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with 3 mg budesonide as active ingredient, every other morning for 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Budenofalk 3mg capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with 3 mg budesonide as active ingredient, every other morning for 52 weeks.

    Arm title
    		 Placebo DB Maintenance
    Arm description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with placebo, every other morning for 52 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Budenofalk placebo capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with placebo, every other morning for 52 weeks.

    Number of subjects in period 1
    		Budesonide DB Maintenance Placebo DB Maintenance
    Started
    44
    48
    Completed
    32
    11
    Not completed
    12
    37
         Adverse event, non-fatal
    3
    2
         Lack of efficacy
    8
    33
         Protocol deviation
    1
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Budesonide DB Maintenance
    Reporting group description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with 3 mg budesonide as active ingredient, every other morning for 52 weeks.

    Reporting group title
    Placebo DB Maintenance
    Reporting group description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with placebo, every other morning for 52 weeks.

    Reporting group values
    		 Budesonide DB Maintenance Placebo DB Maintenance Total
    Number of subjects
    		 44 48 92
    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)
    		 34 30 64
        From 65-84 years
    		 10 18 28
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.7 ± 9.9 60.8 ± 11.7 -
    Gender categorical
    Units: Subjects
        Female
    		 40 38 78
        Male
    		 4 10 14
    Ethnic Group
    Units: Subjects
        White
    		 44 48 92
    Body Mass Index (BMI)
    Units: kg/m2
        arithmetic mean (standard deviation)
    		 26 ± 4.5 24.6 ± 3.8 -
    Mean number of stools/day
    Units: number of stools/day
        arithmetic mean (standard deviation)
    		 1.7 ± 0.6 1.8 ± 0.9 -
    Mean number of watery stools/day
    Units: Number of watery stools/day
        arithmetic mean (standard deviation)
    		 0.1 ± 0.2 0.2 ± 1 -
    Quality of life - Symptom burden
    Assessed by using the visual analogue scale (0-100) for Symptom burden of the SHS (Short Health Scale), with higher scores presenting lower quality of life
    Units: Score
        median (inter-quartile range (Q1-Q3))
    		 6 (2 to 14) 6 (2 to 21) -
    Qualit yof life - Social function
    Assessed by using the visual analogue scale for Social function (0-100) of the SHS (Short Health Scale), with higher scores presenting lower quality of life
    Units: Score
        median (inter-quartile range (Q1-Q3))
    		 3 (2 to 11.5) 3 (1 to 8) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Budesonide DB Maintenance
    Reporting group description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with 3 mg budesonide as active ingredient, every other morning for 52 weeks.

    Reporting group title
    Placebo DB Maintenance
    Reporting group description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with placebo, every other morning for 52 weeks.

    Primary: Number (%) of patients with clinical remission over 52 weeks

    		 Close Top of page
    End point title
    		 Number (%) of patients with clinical remission over 52 weeks
    End point description
    Proportion of patients being in clinical remission over 52 weeks, with clinical remission defined as a mean of < 3 stools/day, thereof a mean of < 1 watery stool/day during the week prior to the final visit (and with no relapses during the 1-year course). Stool consistency was described by patients according to the Bristol Stool Chart.
    End point type
    Primary
    End point timeframe
    52 weeks
    End point values
    		 Budesonide DB Maintenance Placebo DB Maintenance
    Number of subjects analysed
    44
    48
    Units: Number of patients
    27
    8
    Attachments
    		 Primary efficacy endpoint
    Statistical analysis title
    		 Final Analysis (FAS)
    Comparison groups
    Budesonide DB Maintenance v Placebo DB Maintenance
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.0001 [2]
    Method
    		 Normal approximation test
    Parameter type
    		 Risk difference (RD)
    Point estimate
    44.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 26.9
         upper limit
    		 62.7
    Notes
    [1] - The null hypothesis given below will be tested against the alternative hypothesis (α = 0.025, one-sided): Null hypothesis: H0: πA – πB ≤ 0 Alternative hypothesis: H1: πA – πB > 0 Group A (Verum) vs. Group B (Placebo): πA and πB denote the proportion of patients with clinical remission For confirmatory hypothesis testing the inverse normal method of combining the p-values of the normal approximation-test for comparing two rates will be used.
    [2] - The hypothesis test for treatment difference yielded to a one-sided overall p-value of <0.0001 with a corresponding inverse test statistic of 4.415. This was above the pre-defined critical value of 1.967.

    Secondary: Time to treatment failure

    		 Close Top of page
    End point title
    		 Time to treatment failure
    End point description
    The time to treatment failure has been defined as the number of days between randomisation for the DB phase and seven days before the date of the visit where the remission criteria were not fulfilled anymore. Respective Kaplan-Meier analyses have been performed including Kaplan-Meier curves and the calculation of the mean and median time to treatment failure. Patients withdrawing from the study due to any other reasons than treatment failure and patients with maintaining clinical remission have been considered as censored up from their final visit.
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    		 Budesonide DB Maintenance Placebo DB Maintenance
    Number of subjects analysed
    44
    48
    Units: Days
        arithmetic mean (standard error)
    268.1 ± 19.5
    111.4 ± 17.3
    Attachments
    		 Timt to treatment failure
    Statistical analysis title
    		 Kaplan-Meier Analysis - Time to treatment failure
    Comparison groups
    Budesonide DB Maintenance v Placebo DB Maintenance
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Confidence interval

    Secondary: Quality of life - Symptom burden

    		 Close Top of page
    End point title
    		 Quality of life - Symptom burden
    End point description
    Assessed by using the visual analogue scale (0-100) for Symptom burden of the SHS (Short Health Scale), with higher scores presenting lower quality of life.
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    		 Budesonide DB Maintenance Placebo DB Maintenance
    Number of subjects analysed
    44
    48
    Units: Score
        median (inter-quartile range (Q1-Q3))
    5.5 (2 to 30.5)
    75 (19 to 91)
    Attachments
    		 Quality of life
    No statistical analyses for this end point

    Secondary: Quality of life - Social function

    		 Close Top of page
    End point title
    		 Quality of life - Social function
    End point description
    Assessed by using the visual analogue scale (0-100) for Social Function of the SHS (Short Health Scale), with higher scores presenting lower quality of life.
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    		 Budesonide DB Maintenance Placebo DB Maintenance
    Number of subjects analysed
    44
    48
    Units: Score
        median (inter-quartile range (Q1-Q3))
    5.5 (2 to 28.5)
    63 (11 to 85)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    52 weeks
    Adverse event reporting additional description
    It is noteworthy to mention that DB treatment with budesonide was more than twice as long as treatment with placebo (291.2 [125.1] days versus 138.1 [141.51] days; mean [SD]).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Budesonide DB Maintenance
    Reporting group description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with 3 mg budesonide as active ingredient, every other morning for 52 weeks.

    Reporting group title
    Placebo DB Maintenance
    Reporting group description
    		 Patients randomized to this treatment arm received alternating administration of 2 and 1 capsule(s), each containing gastro-resistant pellets with placebo, every other morning for 52 weeks.

    Serious adverse events
    		 Budesonide DB Maintenance Placebo DB Maintenance
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 44 (11.36%)
    2 / 48 (4.17%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Spinal nerve stimulator implantation
    Additional description: Implantation of neurostimulator on dorsal column of spinal record
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transurethral prostatectomy
    Additional description: Transurethral resection of the prostate gland (elective)
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Gallbladder polyp
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Foot deformity
    Additional description: Hospitalisation because of planned Hallux valgus surgery
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Budesonide DB Maintenance Placebo DB Maintenance
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 44 (22.73%)
    5 / 48 (10.42%)
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 44 (4.55%)
    3 / 48 (6.25%)
         occurrences all number
    2
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 44 (9.09%)
    2 / 48 (4.17%)
         occurrences all number
    4
    2
    Urinary tract infection
         subjects affected / exposed
    4 / 44 (9.09%)
    0 / 48 (0.00%)
         occurrences all number
    4
    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/25425655
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 08 08:52:04 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA