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   43865   clinical trials with a EudraCT protocol, of which   7286   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:
    Phase II, open, adaptive, dose escalating, multicentre titration study to assess the efficacy and safety of repeated subcutaneous administration of different doses of BIM 23A760 in patients with carcinoid syndrome

    Summary
    EudraCT number
    		 2009-013222-16
    Trial protocol
    		 SE   NL   LV   CZ   FI   IE   ES   BE   AT   FR   DE   IT   SK   GB  
    Global end of trial date
    15 Dec 2010

    Results information
    Results version number
    		 v2(current)
    This version publication date
    27 Feb 2016
    First version publication date
    12 Aug 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Review and correction.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    8-55-52060-004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ipsen Pharma
    Sponsor organisation address
    65 quai Georges Gorse, Boulogne-Billancourt, France, 92100
    Public contact
    Ipsen Pharma, Ipsen Pharma, 33.(0).1 1.58.33.50.00, clinical.trials@ipsen.com
    Scientific contact
    Ipsen Pharma, Ipsen Pharma, 33.(0).1 1.58.33.50.00, clinical.trials@ipsen.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 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Dec 2010
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Dec 2010
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the efficacy of repeated s.c. injections at different doses of BIM 23A760 on patient’s overall satisfaction in terms of symptom relief (diarrhoea and/or flushes) in patients with carcinoid syndrome after 24 weeks of treatment.
    Protection of trial subjects
    This clinical study was designed and implemented and reported in accordance with the International Conference on Harmonisation (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Feb 2010
    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
    Russian Federation: 1
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Finland: 1
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Ireland: 1
    Worldwide total number of subjects
    8
    EEA total number of subjects
    7
    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)
    8
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was terminated prematurely. Only 8 patients were treated in part A and no patients participated in part B.

    Pre-assignment
    Screening details
    		 Patients screened were 15 and not treated were 7 (2 subjects were not included due to early termination of study by sponsor and 5 subjects failed to meet inclusion criteria).

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 BIM 23A760
    Arm description
    		 This dose adaptive study is planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed are 1, 2, 4, 6 and 8 mg, however, the maximum starting dose will be 4 mg. The starting dose of the first cohort will be 1 mg; the first cohort will include at least five patients. After the first fifteen patients have been treated for 4 weeks, the results will be reviewed by a Data Review Committee. An extension phase (Part B) is planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760: BIM 23A760 is a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 dose of 1, 2, 4, 6 and 8 mg can be given to the patient according to a dose escalation and titration process. Patients will receive 24 weekly injections of BIM 23A760 during the treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BIM 23A760
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 mg, 2 mg, 4 mg

    Number of subjects in period 1
    		BIM 23A760
    Started
    8
    BIM 23A760 1 mg
    3
    BIM 23A760 2 mg
    2
    BIM 23A760 4 mg
    3
    Completed
    0
    Not completed
    8
         Consent withdrawn by subject
    1
         Adverse event, non-fatal
    2
         Study termination by sponsor
    5

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    		 This dose adaptive study is planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed are 1, 2, 4, 6 and 8 mg, however, the maximum starting dose will be 4 mg. The starting dose of the first cohort will be 1 mg; the first cohort will include at least five patients. After the first fifteen patients have been treated for 4 weeks, the results will be reviewed by a Data Review Committee. An extension phase (Part B) is planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760: BIM 23A760 is a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 dose of 1, 2, 4, 6 and 8 mg can be given to the patient according to a dose escalation and titration process. Patients will receive 24 weekly injections of BIM 23A760 during the treatment period.

    Reporting group values
    		 Overall Trial Total
    Number of subjects
    		 8 8
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 8 8
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.1 ( 6.88 ) -
    Gender categorical
    Units: Subjects
        Female
    		 6 6
        Male
    		 2 2
    Race/Ethnicity
    Units: Subjects
        Caucasian/ White
    		 8 8
    Diabetic status
    Units: Subjects
        Diabetic
    		 0 0
        Nondiabetic
    		 8 8
    Post-menopausal status
    Units: Subjects
        Yes
    		 6 6
        No
    		 0 0
        N/A - Not applicable
    		 2 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    BIM 23A760
    Reporting group description
    		 This dose adaptive study is planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed are 1, 2, 4, 6 and 8 mg, however, the maximum starting dose will be 4 mg. The starting dose of the first cohort will be 1 mg; the first cohort will include at least five patients. After the first fifteen patients have been treated for 4 weeks, the results will be reviewed by a Data Review Committee. An extension phase (Part B) is planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760: BIM 23A760 is a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 dose of 1, 2, 4, 6 and 8 mg can be given to the patient according to a dose escalation and titration process. Patients will receive 24 weekly injections of BIM 23A760 during the treatment period.

    Primary: Percentage of Patients With a Positive Overall Satisfactory Relief of Symptoms (Diarrhoea and/or Flushes) on the Likert Scale

    		 Close Top of page
    End point title
    		 Percentage of Patients With a Positive Overall Satisfactory Relief of Symptoms (Diarrhoea and/or Flushes) on the Likert Scale [1]
    End point description
    Patient satisfaction based on a Likert scale from 0-5 (0 being not satisfied and 5 being completely satisfied) Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    End point type
    Primary
    End point timeframe
    Week 24
    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: Due to premature termination of the study, no data was collected/analyzed and no patient participated in Part B.
    End point values
    		 BIM 23A760
    Number of subjects analysed
    0 [2]
    Units: Perceentage of participants
    Notes
    [2] - Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    No statistical analyses for this end point

    Secondary: Percentage of Patients With Improvement in Symptoms (Diarrhoea and/or Flushes)

    		 Close Top of page
    End point title
    		 Percentage of Patients With Improvement in Symptoms (Diarrhoea and/or Flushes)
    End point description
    Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Up to week 24
    End point values
    		 BIM 23A760
    Number of subjects analysed
    0 [3]
    Units: Percentage of participants
    Notes
    [3] - Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    No statistical analyses for this end point

    Secondary: Change in the Quality of Life (QoL) Assessment

    		 Close Top of page
    End point title
    		 Change in the Quality of Life (QoL) Assessment
    End point description
    Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 BIM 23A760
    Number of subjects analysed
    0 [4]
    Units: Percentage of participants
    Notes
    [4] - Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    No statistical analyses for this end point

    Secondary: Change in 5 Hydroxyindoleacetic Acid (5 HIAA) and Chromogranin A

    		 Close Top of page
    End point title
    		 Change in 5 Hydroxyindoleacetic Acid (5 HIAA) and Chromogranin A
    End point description
    Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 BIM 23A760
    Number of subjects analysed
    0 [5]
    Units: Percentage of participants
    Notes
    [5] - Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    No statistical analyses for this end point

    Secondary: Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s)

    		 Close Top of page
    End point title
    		 Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s)
    End point description
    Analysis Population Description: Both ITT (Intent-To-Treat) and safety populations were the same analysis group. Treatment emergent adverse events (TEAE) reported by 2 or more patients (safety population) by primary system organ class.
    End point type
    Secondary
    End point timeframe
    Up to week 26
    End point values
    		 BIM 23A760
    Number of subjects analysed
    8
    Units: Participants
        General Disorders & Administration Site Condition
    5
        Gastrointestinal Disorder
    4
        Nervous System Disorders
    3
        Infections and Infestations
    2
        Metabolism and Nutritional Disorders
    2
        Neoplasms Benign, Malignant and unspecified
    2
        Reproductive System and Breast Disorders
    2
    No statistical analyses for this end point

    Secondary: Minimum Concentration (Cmin) BIM 23A760 Plasma Levels

    		 Close Top of page
    End point title
    		 Minimum Concentration (Cmin) BIM 23A760 Plasma Levels
    End point description
    Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At 9 timepoints up to 1 week after 24th administration in week 24
    End point values
    		 BIM 23A760
    Number of subjects analysed
    0 [6]
    Units: Percentage of participants
    Notes
    [6] - Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    No statistical analyses for this end point

    Secondary: Concentration at 2 Hours Postdose (C2 Hours) BIM 23A760 Plasma LevelsStudy was prematurely terminated and no data was collected/analyzed for this outcome measure.

    		 Close Top of page
    End point title
    		 Concentration at 2 Hours Postdose (C2 Hours) BIM 23A760 Plasma LevelsStudy was prematurely terminated and no data was collected/analyzed for this outcome measure.
    End point description
    Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    At 8 timepoints up to week 24
    End point values
    		 BIM 23A760
    Number of subjects analysed
    0 [7]
    Units: Percentage of participants
    Notes
    [7] - Study was prematurely terminated and no data was collected/analyzed for this outcome measure.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to week 26
    Adverse event reporting additional description
    Dose received prior to to AE onset Two SAEs 'Confusional State' and 'Nausea' were not included as they occurred during screening phase, before starting study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.0
    Reporting groups
    Reporting group title
    BIM 23A760
    Reporting group description
    		 This dose adaptive study was planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed were 1, 2, 4, 6 and 8 mg; however, the maximum starting dose was 4 mg. The starting dose of the first cohort was 1 mg and the first cohort would include at least five patients. After the first 15 patients were treated for 4 weeks, the results were to be reviewed by a Data Review Committee. An extension phase (Part B) was planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760 was a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 doses of 1, 2, 4, 6 and 8 mg were to be given to the patient according to a dose escalation and titration process. Patients would have received 24 weekly injections of BIM 23A760 during the treatment period.

    Serious adverse events
    		 BIM 23A760
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 8 (12.50%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 BIM 23A760
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 8 (75.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to liver
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Metastases to peripheral vascular system
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Fatigue
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Injection site inflammation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Injection site pain
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    3
    Injection site pruritus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Injection site reaction
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Oedema
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Pelvic floor muscle weakness
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Vulvovaginal dryness
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Headache
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Lethargy
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 8 (37.50%)
         occurrences all number
    3
    Abdominal pain
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Constipation
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Vomiting
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    3
    Abdominal distension
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Dyspepsia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Mucous stools
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Erythema
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Night sweats
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Groin pain
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Systemic lupus erythematosus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Sinusitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    3
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Jan 2010
    Amendment 1 • The initial cohort to be treated at 1 mg was expanded to include a minimum of 15 patients and a maximum of 40 patients. • The scope of the DRC review was expanded to include pharmacokinetic data. • The exclusion criteria were amended so that patients who had received a radiolabelled SRL for reasons other than carcinoid syndrome treatment could be included in the study. • The exclusion criteria were reworded in line with the Phase II BIM 23A760 study in patients with acromegaly (Study 2-55-52060-003), to exclude patients with a known hypersensitivity to any compounds related to the test materials and/or any known contraindications to MRI/CT. • Changes relating to the withdrawal criteria which were requested by the German Competent Authorities for Study 2-55-52060-003 were also implemented for this study, to provide more comprehensive guidance on when and how to withdraw patients. • Two exclusion criteria, one regarding impaired creatinine clearance and one regarding fibrosis, were added at the request of the Competent Authority in Ireland. • For clarification of the tumour localisation, the exclusion criteria were reworded to specifically exclude patients with tumours of foregut or hindgut origin; only patients with tumours of midgut origin were eligible for the study. • Visit 1 hospitalisation was made optional because no study drug was administered at this visit and all assessments could be conducted without hospitalisation. • Other minor corrections and amendments were made to clarify certain procedures and to remove inconsistencies.
    30 Apr 2010
    Protocol amendment 2 • An extension phase was added to allow patients to continue treatment with BIM 23A760 in the study after completing 6 months of treatment, and to assess long term safety and efficacy of BIM 23A760 in patients with carcinoid syndrome. • The inclusion criterion regarding contraception was reworded to meet regulatory guidance for clinical trials where the potential interactions between the IMP and hormonal contraceptives were not yet known (CPMP/ICH/286/95). • The procedure to be followed in the event of a pregnancy was clarified; i.e. the IMP was to be discontinued and the patient had to be withdrawn from the study.

    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.
    Due to premature termination of the study, no data was collected/analyzed and no patient participated in Part B.
    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 Apr 27 05:37:46 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA