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    Clinical Trial Results:
    PHASE II, OPEN, RANDOMISED, PARALLEL GROUP, NONCOMPARATIVE MULTICENTRE STUDY TO ASSESS THE EFFICACY AND SAFETY OF REPEATED SUBCUTANEOUS (S.C.) ADMINISTRATION OF DIFFERENT DOSES OF BIM 23A760 IN ACROMEGALIC PATIENTS

    Summary
    EudraCT number
    		 2009-010787-42
    Trial protocol
    		 SE   BE   NL   GB   LV   DE   FR   LT   CZ   IT   PL  
    Global end of trial date
    11 Feb 2011

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Mar 2016
    First version publication date
    16 Mar 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    2-55-52060-003
    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, 331 58335000, clinical.trials@ipsen.com
    Scientific contact
    Ipsen Pharma, Ipsen Pharma, 331 58335000, 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
    28 Nov 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Feb 2011
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Feb 2011
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Part A: To assess the efficacy of repeated s.c. injections at different doses of BIM 23A760 on growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in acromegalic patients after 6 months of treatment. Part B: To assess the long term safety of weekly injections of BIM 23A760 in patients with acromegaly.
    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
    09 Nov 2009
    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
    Brazil: 10
    Country: Number of subjects enrolled
    Mexico: 11
    Country: Number of subjects enrolled
    Ukraine: 20
    Country: Number of subjects enrolled
    United States: 3
    Country: Number of subjects enrolled
    Poland: 2
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Romania: 12
    Country: Number of subjects enrolled
    Sweden: 1
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Czech Republic: 3
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Latvia: 1
    Country: Number of subjects enrolled
    Lithuania: 6
    Worldwide total number of subjects
    76
    EEA total number of subjects
    32
    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)
    74
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a multicentre study conducted at 36 investigational sites in 16 countries: Czech Republic, Lithuania, Poland, Romania, Ukraine, Latvia, USA, United Kingdom (UK), Italy, Mexico, Brazil, France, Belgium, Netherlands, Germany and Sweden.

    Pre-assignment
    Screening details
    		 Screened subjects were 109 and screen failures were 33. Subjects randomised and treated in part A were 76. Subjects completed part A were 21 and subjects entered Part B were 12, excluding 9 subjects, who chose not to continue in part B. No subjects completed the study.

    Period 1
    Period 1 title
    ITT (Intention-to-Treat) - Part A
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part A-Arm A: BIM 23A760 1 mg
    Arm description
    		 BIM 23A760 1 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

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

    Arm title
    		 Part A-Arm B: BIM 23A760 2 mg
    Arm description
    		 BIM 23A760 2 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

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

    Arm title
    		 Part A-Arm C: BIM 23A760 4 mg
    Arm description
    		 BIM 23A760 4 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

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

    Arm title
    		 Part A-Arm D: BIM 23A760 6 mg
    Arm description
    		 BIM 23A760 6 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BIM 23A760 6 mg
    Investigational medicinal product code
    BIM 23A760 6 mg
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    6 mg

    Number of subjects in period 1
    		Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg
    Started
    19
    19
    18
    20
    Completed
    5
    6
    5
    5
    Not completed
    14
    13
    13
    15
         Withdrawn - Study termination by sponsor
    13
    12
    13
    14
         Consent withdrawn by subject
    -
    -
    -
    1
         Adverse event, non-fatal
    -
    1
    -
    -
         Lost to follow-up
    1
    -
    -
    -
    Period 2
    Period 2 title
    ITT (Intention-to-Treat) - Part B
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part B-Arm A: BIM 23A760 1 mg
    Arm description
    		 BIM 23A760 1 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

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

    Arm title
    		 Part B-Arm B: BIM 23A760 2 mg
    Arm description
    		 BIM 23A760 2 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

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

    Arm title
    		 Part B-Arm C: BIM 23A760 4 mg
    Arm description
    		 BIM 23A760 4 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

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

    Arm title
    		 Part B-Arm D: BIM 23A760 6 mg
    Arm description
    		 BIM 23A760 6 mg subcutaneous 24 weekly injections.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BIM 23A760 6 mg
    Investigational medicinal product code
    BIM 23A760 6 mg
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    6 mg

    Number of subjects in period 2 [1]
    		Part B-Arm A: BIM 23A760 1 mg Part B-Arm B: BIM 23A760 2 mg Part B-Arm C: BIM 23A760 4 mg Part B-Arm D: BIM 23A760 6 mg
    Started
    4
    3
    2
    3
    Received maximum dose of 1 mg
    0
    0
    0
    0
    Received maximum dose of 2 mg
    3
    0
    0
    0
    Received maximum dose of 4 mg
    1
    3
    0
    0
    Received maximum dose of 6 mg
    0
    0
    2
    3
    Completed
    0
    0
    0
    0
    Not completed
    4
    3
    2
    3
         Withdrawn - Study termination by sponsor
    4
    3
    2
    2
         Consent withdrawn by subject
    -
    -
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 1 subject did not enter Part B Arm A 3 subjects did not enter Part B Arm B 3 subjects did not enter Part B Arm C 2 subjects did not enter Part B Arm D

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part A-Arm A: BIM 23A760 1 mg
    Reporting group description
    		 BIM 23A760 1 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A-Arm B: BIM 23A760 2 mg
    Reporting group description
    		 BIM 23A760 2 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A-Arm C: BIM 23A760 4 mg
    Reporting group description
    		 BIM 23A760 4 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A-Arm D: BIM 23A760 6 mg
    Reporting group description
    		 BIM 23A760 6 mg subcutaneous 24 weekly injections.

    Reporting group values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg Total
    Number of subjects
    		 19 19 18 20 76
    Age categorical
    Units: Subjects
        Adults (20-74 Years)
    		 19 19 18 20 76
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 42.8 ± 11.3 48.7 ± 11.2 40.3 ± 11.3 43.4 ± 12.9 -
    Gender categorical
    Units: Subjects
        Female
    		 10 13 6 13 42
        Male
    		 9 6 12 7 34
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian/White
    		 17 14 13 18 62
        Multiple race
    		 2 5 5 2 14
    Region of Enrollment
    ITT
    Units: Subjects
        Belgium
    		 1 1 0 0 2
        Brazil
    		 1 1 3 5 10
        Czech Republic
    		 1 1 0 1 3
        Lithuania
    		 1 1 3 1 6
        Mexico
    		 2 4 4 1 11
        Netherlands
    		 2 0 0 1 3
        Poland
    		 1 1 0 0 2
        Romania
    		 4 3 1 4 12
        Ukraine
    		 6 4 4 6 20
        France
    		 0 1 0 1 2
        United States
    		 0 2 1 0 3
        Latvia
    		 0 0 1 0 1
        Sweden
    		 0 0 1 0 1
    Diabetic status at entry
    Units: Subjects
        Diabetic
    		 2 1 2 2 7
        Non-diabetic
    		 17 18 16 18 69
    Height
    Units: Cm
        arithmetic mean (standard deviation)
    		 170.1 ± 8.1 170.3 ± 13.2 175 ± 10.1 166.4 ± 8.6 -
    Insulin-like growth factor 1 (IGF-1)
    Units: Percentage of ULN
        median (full range (min-max))
    		 307 (146 to 690) 315 (176 to 508) 382 (168 to 549) 335 (157 to 539) -
    Growth Hormone
    Units: ng/mL
        arithmetic mean (standard deviation)
    		 16.79 ± 24.56 20.99 ± 59.28 28.6 ± 64.83 26.59 ± 63.47 -
    Baseline Prolactin (Males)
    Units: μg/L
        arithmetic mean (standard deviation)
    		 11.506 ± 14.233 34.113 ± 49.588 41.657 ± 60.965 83.036 ± 131.024 -
    Baseline Prolactin (Pre-menopausal females)
    Units: μg/L
        arithmetic mean (standard deviation)
    		 19.838 ± 15.247 26.158 ± 19.798 35.608 ± 25.536 23.634 ± 23.778 -
    Baseline Prolactin (Post-menopausal females)
    Units: μg/L
        arithmetic mean (standard deviation)
    		 8.42 ± 3.167 16.409 ± 24.232 7.87 ± 0.693 25.118 ± 39.986 -
    Ring Finger Circumference
    Number of Patients Analysed at Baseline: Arm A: 4 Arm B: 4 Arm C: 3 Arm D: 4
    Units: mm
        arithmetic mean (standard deviation)
    		 70.2 ± 5.6 68.5 ± 6.2 71.2 ± 4.7 68.4 ± 6.3 -

    End points

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    End points reporting groups
    Reporting group title
    Part A-Arm A: BIM 23A760 1 mg
    Reporting group description
    		 BIM 23A760 1 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A-Arm B: BIM 23A760 2 mg
    Reporting group description
    		 BIM 23A760 2 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A-Arm C: BIM 23A760 4 mg
    Reporting group description
    		 BIM 23A760 4 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A-Arm D: BIM 23A760 6 mg
    Reporting group description
    		 BIM 23A760 6 mg subcutaneous 24 weekly injections.
    Reporting group title
    Part B-Arm A: BIM 23A760 1 mg
    Reporting group description
    		 BIM 23A760 1 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part B-Arm B: BIM 23A760 2 mg
    Reporting group description
    		 BIM 23A760 2 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part B-Arm C: BIM 23A760 4 mg
    Reporting group description
    		 BIM 23A760 4 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part B-Arm D: BIM 23A760 6 mg
    Reporting group description
    		 BIM 23A760 6 mg subcutaneous 24 weekly injections.

    Subject analysis set title
    Overall - Part A
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Overall subjects in Part A (BIM 23A760 1 mg, 2 mg, 4 mg and 6 mg)

    Subject analysis set title
    Overall - Part B
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Overall subjects in Part B (BIM 23A760 2 mg, 4 mg and 6 mg)

    Primary: Percentage of subjects with mean GH ≤2.5 ng/mL and normalised IGF-1

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    End point title
    		 Percentage of subjects with mean GH ≤2.5 ng/mL and normalised IGF-1 [1]
    End point description
    Intention-to-Treat (ITT) population: All randomized subjects who received at least one dose of study medication. N=Number of subjects attended Month 6 (visit 9).
    End point type
    Primary
    End point timeframe
    At Month 6
    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: No statistical analysis performed.
    End point values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg
    Number of subjects analysed
    6
    7
    5
    5
    Units: Percentage of subjects
    number (not applicable)
        Yes
    0
    0
    0
    0
        No
    8.3
    100
    100
    100
        Missing
    16.7
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Mean GH≤2.5 ng/mL and Normalised IGF-1

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    End point title
    		 Percentage of Subjects With Mean GH≤2.5 ng/mL and Normalised IGF-1
    End point description
    ITT population. N=Number of subjects attended Month 3 (visit 7).
    End point type
    Secondary
    End point timeframe
    At Month 3
    End point values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg
    Number of subjects analysed
    12
    13
    12
    13
    Units: Percentage of subjects
    number (not applicable)
        Yes
    0
    0
    0
    7.7
        No
    100
    100
    100
    92.3
        Missing
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Mean GH≤2.5 ng/mL and Normalised IGF-1

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    End point title
    		 Percentage of Subjects With Mean GH≤2.5 ng/mL and Normalised IGF-1
    End point description
    ITT population. N=Number of subjects attended Month 1 (visit 5).
    End point type
    Secondary
    End point timeframe
    At Month 1
    End point values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg
    Number of subjects analysed
    19
    18
    18
    20
    Units: Percentage of subjects
    number (not applicable)
        Yes
    5.3
    0
    0
    5
        No
    94.7
    100
    100
    95
        Missing
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in the Mean GH From 0-3 Hours at Months 1, 3 and 6

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    End point title
    		 Percent Change From Baseline in the Mean GH From 0-3 Hours at Months 1, 3 and 6
    End point description
    Percentage change from Baseline at month X = (Mean GH at month X - Mean GH at baseline) x 100 / Mean GH at baseline N=Number of patients randomized to treatment in IGF-1 <2.5 x upper limit of normal (ULN) stratum and IGF-1 ≥2.5 x ULN stratum.
    End point type
    Secondary
    End point timeframe
    0-3 hr on Baseline (Day 1) and Months 1, 3 and 6
    End point values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg
    Number of subjects analysed
    15
    15
    15
    16
    Units: Percentage of change in mean GH
    arithmetic mean (standard deviation)
        At Month 1: IGF-1<2.5xULN
    4.1 ± 53.03
    -0.55 ± 23.98
    -9.92 ± 71.51
    -17.59 ± 41.82
        At Month 3: IGF-1<2.5xULN
    29.26 ± 45.97
    -18.99 ± 21.36
    17.48 ± 127.97
    -28.84 ± 43.25
        At Month 6: IGF-1<2.5xULN
    71.44 ± 35.97
    3.32 ± 9.09
    82.45 ± 0
    -38.21 ± 27.27
        At Month 1: IGF-1≥2.5xUL
    -39.2 ± 30.33
    -22.24 ± 34.72
    -10.64 ± 51.18
    -23.63 ± 39.57
        At Month 3: IGF-1≥2.5xUL
    -26.14 ± 39.6
    -22.35 ± 31.71
    -7.64 ± 30.11
    -20.53 ± 42.23
        At Month 6: IGF-1≥2.5xUL
    -36.15 ± 45.63
    15.28 ± 82.56
    -10.43 ± 28.9
    -19.47 ± 68.9
    No statistical analyses for this end point

    Secondary: Changes in IGF-1

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    End point title
    		 Changes in IGF-1
    End point description
    ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Month 6
    End point values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg
    Number of subjects analysed
    19
    19
    18
    20
    Units: Percentage of change in IGF-1
        arithmetic mean (standard deviation)
    -51.3 ± 136.66
    -53.31 ± 80.57
    -40.53 ± 56.65
    -85.91 ± 95.34
    No statistical analyses for this end point

    Secondary: Percentage Change in Ring Finger Circumference

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    End point title
    		 Percentage Change in Ring Finger Circumference
    End point description
    Percentage change from Baseline at month X = (Ring finger circumference at month X - ring finger circumference at baseline) x 100 / ring finger circumference at baseline. ITT population. N=Number of subjects attended Month 6 (visit 9). Circ = Circumference
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Month 6
    End point values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg
    Number of subjects analysed
    6
    7
    5
    5
    Units: percentage of Change in Ring Finger circ
        arithmetic mean (standard deviation)
    -3.518 ± 3.688
    -1.469 ± 2.12
    -0.678 ± 2.409
    -4.003 ± 3.367
    No statistical analyses for this end point

    Secondary: Number of Subjects Reported Adverse Events During the Study

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    End point title
    		 Number of Subjects Reported Adverse Events During the Study
    End point description
    For summaries of intensity and causality, individual patients may be reported in more than one category. In the event of multiple episodes of AEs being reported by the same patient during the study, the maximum intensity (severe > moderate > mild) and the most serious causality (related > not related) have been chosen. TEAE (Treatment emergent adverse event) are reported by Maximum Dose Received in Each Part of the Study. Analysis Population Description: Safety Population Number of subjects analysed: Arm: Part B-Arm C: BIM 23A760 4 mg=4 Arm: Part B-Arm D: BIM 23A760 6 mg=5
    End point type
    Secondary
    End point timeframe
    Up to Visit 10 (An average of 6.5 Months)
    End point values
    		 Part A-Arm A: BIM 23A760 1 mg Part A-Arm B: BIM 23A760 2 mg Part A-Arm C: BIM 23A760 4 mg Part A-Arm D: BIM 23A760 6 mg Part B-Arm B: BIM 23A760 2 mg Part B-Arm C: BIM 23A760 4 mg Part B-Arm D: BIM 23A760 6 mg Overall - Part A Overall - Part B
    Number of subjects analysed
    19
    19
    18
    20
    3
    2
    3
    76
    12
    Units: Number of subjects
        Severe
    0
    1
    1
    2
    0
    0
    0
    4
    0
        Moderate
    3
    8
    4
    7
    0
    0
    3
    22
    3
        Mild
    11
    9
    12
    15
    0
    1
    1
    47
    2
        Related
    7
    8
    10
    11
    0
    0
    1
    36
    1
        Not Related
    8
    9
    6
    11
    0
    1
    3
    34
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Visit 10 (An average of 6.5 Months)
    Adverse event reporting additional description
    Included Serious Adverse Events (SAEs) and Adverse Events (AEs) during treatment phase for Safety Population TEAE are reported by Maximum Dose Received in Each Part of the Study. 4 subjects from part B, Arm A were considered under other arms of part B based on the maximum dose received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.1
    Reporting groups
    Reporting group title
    Part A: Arm A: BIM 23A760 1 mg
    Reporting group description
    		 BIM 23A760 1 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A: Arm B: BIM 23A760 2 mg
    Reporting group description
    		 BIM 23A760 2 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A: Arm C: BIM 23A760 4 mg
    Reporting group description
    		 BIM 23A760 4 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part A: Arm D: BIM 23A760 6 mg
    Reporting group description
    		 BIM 23A760 6 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part B: Arm B: BIM 23A760 2 mg
    Reporting group description
    		 -

    Reporting group title
    Part B: Arm C: BIM 23A760 4 mg
    Reporting group description
    		 BIM 23A760 4 mg subcutaneous 24 weekly injections.

    Reporting group title
    Part B: Arm D: BIM 23A760 6 mg
    Reporting group description
    		 BIM 23A760 6 mg subcutaneous 24 weekly injections.

    Reporting group title
    Overall - Part A
    Reporting group description
    		 -

    Reporting group title
    Overall - Part B
    Reporting group description
    		 -

    Serious adverse events
    		 Part A: Arm A: BIM 23A760 1 mg Part A: Arm B: BIM 23A760 2 mg Part A: Arm C: BIM 23A760 4 mg Part A: Arm D: BIM 23A760 6 mg Part B: Arm B: BIM 23A760 2 mg Part B: Arm C: BIM 23A760 4 mg Part B: Arm D: BIM 23A760 6 mg Overall - Part A Overall - Part B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 19 (10.53%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 5 (40.00%)
    3 / 76 (3.95%)
    2 / 12 (16.67%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 76 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Sinusitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 76 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Part A: Arm A: BIM 23A760 1 mg Part A: Arm B: BIM 23A760 2 mg Part A: Arm C: BIM 23A760 4 mg Part A: Arm D: BIM 23A760 6 mg Part B: Arm B: BIM 23A760 2 mg Part B: Arm C: BIM 23A760 4 mg Part B: Arm D: BIM 23A760 6 mg Overall - Part A Overall - Part B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 19 (57.89%)
    12 / 19 (63.16%)
    12 / 18 (66.67%)
    15 / 20 (75.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    4 / 5 (80.00%)
    50 / 76 (65.79%)
    5 / 12 (41.67%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    3 / 18 (16.67%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    4 / 76 (5.26%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    4
    0
    0
    0
    0
    5
    0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Peripheral coldness
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Phlebitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Administration site reaction
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    7
    0
    0
    0
    7
    0
    Application site erythema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Application site induration
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    2
    0
    Asthenia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    2
    0
    Fatigue
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Hyperthermia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Injection site erythema
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    1 / 18 (5.56%)
    3 / 20 (15.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    6 / 76 (7.89%)
    0 / 12 (0.00%)
         occurrences all number
    0
    4
    15
    10
    0
    0
    0
    29
    0
    Injection site induration
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 19 (10.53%)
    4 / 18 (22.22%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    9 / 76 (11.84%)
    0 / 12 (0.00%)
         occurrences all number
    2
    4
    5
    2
    0
    0
    0
    13
    0
    Injection site inflammation
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Injection site nodule
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    2 / 18 (11.11%)
    2 / 20 (10.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    6 / 76 (7.89%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    4
    6
    0
    0
    0
    12
    0
    Injection site pain
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    2 / 18 (11.11%)
    2 / 20 (10.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    4 / 76 (5.26%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    6
    5
    0
    0
    0
    11
    0
    Injection site pruritis
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    3 / 18 (16.67%)
    3 / 20 (15.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    8 / 76 (10.53%)
    0 / 12 (0.00%)
         occurrences all number
    0
    4
    16
    7
    0
    0
    0
    27
    0
    Injection site rash
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Injection site reaction
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    0 / 18 (0.00%)
    2 / 20 (10.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    4 / 76 (5.26%)
    0 / 12 (0.00%)
         occurrences all number
    0
    4
    0
    9
    0
    0
    0
    13
    0
    Injection site swelling
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    2
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Menstruation delayed
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory disorder
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Pollakiuria
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    2
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    2
    0
    Blood amylase increased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Blood glucose increased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Blood pressure decreased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    2 / 18 (11.11%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    3
    0
    Blood pressure diastolic decreased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    2
    0
    Red blood cells urine positive
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Tri-iodothyronine free increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    White blood cells urine positive
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 76 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Wound
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    2
    0
    Nervous system disorders
    Acoustic neuritis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Headache
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    3 / 20 (15.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    4 / 76 (5.26%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    2
    4
    0
    0
    0
    6
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    2 / 20 (10.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    3 / 76 (3.95%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    0
    3
    0
    Pancytopenia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Hyperthyroidism
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Eye disorders
    Eye irritation
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    1 / 18 (5.56%)
    3 / 20 (15.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    6 / 76 (7.89%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    1
    5
    0
    0
    0
    9
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    4 / 76 (5.26%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    0
    0
    4
    0
    Diarrhoea
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 19 (5.26%)
    1 / 18 (5.56%)
    2 / 20 (10.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    6 / 76 (7.89%)
    0 / 12 (0.00%)
         occurrences all number
    3
    1
    10
    7
    0
    0
    0
    21
    0
    Flatulence
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    2 / 18 (11.11%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    5 / 76 (6.58%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    2
    1
    0
    0
    0
    5
    0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 19 (10.53%)
    2 / 18 (11.11%)
    2 / 20 (10.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    8 / 76 (10.53%)
    0 / 12 (0.00%)
         occurrences all number
    2
    3
    3
    5
    0
    0
    0
    13
    0
    Proctalgia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    3 / 76 (3.95%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    0
    3
    0
    Gastritis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 76 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    0 / 76 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Cytolytic hepatitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 5 (0.00%)
    0 / 76 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    2
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    3
    0
    Hyperkeratosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    0
    3
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    2
    0
    Back pain
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 18 (5.56%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Synovitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 19 (5.26%)
    1 / 18 (5.56%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    5 / 76 (6.58%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    1
    2
    0
    0
    0
    6
    0
    Infections and infestations
    Cystitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    3 / 76 (3.95%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    0
    0
    3
    0
    Sinusitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 5 (20.00%)
    2 / 76 (2.63%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    2
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Hyperglycaema
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 18 (0.00%)
    0 / 20 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    1 / 76 (1.32%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Impacted fasting glucose
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 18 (0.00%)
    1 / 20 (5.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 5 (0.00%)
    2 / 76 (2.63%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    3
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Sep 2009
    Amendment 1 The following change was implemented to comply with French regulations: - The eligibility criteria were amended to exclude patients deprived of their freedom/rights and those unable to give consent.
    09 Oct 2009
    Amendment 2 The following changes were implemented: - The exclusion criterion regarding patients deprived of their freedom/rights and those unable to give consent was extended to apply to all countries to ensure homogeneity of the population. - More comprehensive guidance on when and how to withdraw patients was added, following a request by the German Competent Authorities to provide more information.
    09 Dec 2009
    Amendment 3 A dose titration schedule was added for patients in the 2, 4 and 6 mg groups, so that all patients in the study began treatment at 1 mg and then those in the 2, 4 and 6 mg groups had their dose titrated up to the randomised dose. This change was implemented as a result of new PK data in monkeys which showed a 2x higher first peak concentration for the solution formulation compared to the lyophilisate formulation used in previous studies.
    28 Apr 2010
    Amendment 4 An extension phase (Part B) was added.
    09 Sep 2010
    Amendment 5 An administrative change to the fax number for the US PV contact was implemented.

    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 study was terminated prematurely due to lack of efficacy.
    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.

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