Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    EFFICACY AND SAFETY OF ORAL OCTREOLIN™ IN PATIENTS WITH ACROMEGALY WHO ARE CURRENTLY RECEIVING PARENTERAL SOMATOSTATIN ANALOGS

    Summary
    EudraCT number
    		 2011-002912-10
    Trial protocol
    		 HU   NL   GB   DE   SK   PL   IT   SI   LT  
    Global end of trial date
    30 May 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jul 2017
    First version publication date
    30 Jul 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CH-ACM-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01412424
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Chiasma, Inc.
    Sponsor organisation address
    831 Beacon Street, Suite no. 313, Newton Centre, Massachusetts, United States, 02459
    Public contact
    William H. Ludlam, Sr. VP Clinical Development and Medical Affairs, Chiasma, Inc., +1 617 928 5294, william.ludlam@chiasmapharma.com
    Scientific contact
    Asi Haviv, VP Clinical Development, Chiasma, Inc., +972 8 939 3888, Asi@chiasmapharma.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
    30 May 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 May 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    30 May 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the effect of Octreolin therapy on Insulin-like Growth Factor 1 (IGF-1) levels and Growth Hormone (GH) levels as measures of response
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Mar 2012
    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
    Netherlands: 17
    Country: Number of subjects enrolled
    Poland: 14
    Country: Number of subjects enrolled
    Slovakia: 4
    Country: Number of subjects enrolled
    Slovenia: 4
    Country: Number of subjects enrolled
    United Kingdom: 12
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    Hungary: 21
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Lithuania: 7
    Country: Number of subjects enrolled
    Israel: 17
    Country: Number of subjects enrolled
    Mexico: 16
    Country: Number of subjects enrolled
    Romania: 12
    Country: Number of subjects enrolled
    Serbia: 13
    Worldwide total number of subjects
    155
    EEA total number of subjects
    109
    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)
    127
    From 65 to 84 years
    28
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study comprised a Core Treatment Period (consisting of a Dose Escalation Phase and a Fixed Dose Phase) followed by a voluntary Extension Period. The optimum dose identified for each patient during the Dose Escalation Phase was maintained in the Fixed Dose Phase and the Extension Period.

    Pre-assignment
    Screening details
    		 At least 150 adult patients who were diagnosed with acromegaly and who, at screening, were receiving regular parenteral therapy at a stable dose of an SRL for at least 3 months, and who were responders, were to be enrolled.

    Period 1
    Period 1 title
    Core Treatment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Octreotide capsules
    Arm description
    		 All patients
    Arm type
    		 Experimental

    Investigational medicinal product name
    Octreotide 20 mg capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Oral octreotide treatment was started at a dose of 40 mg/day (20 mg bid). Dose escalation was based on measurement of the patient’s IGF-1 levels and acromegaly-related symptoms. The dose was titrated on an individual basis, stepwise from 40 mg/day to 60 mg/day (40 mg in the morning, 20 mg in the evening) to a maximum of 80 mg/day (40 mg bid) until maximum hormonal suppression was achieved.

    Number of subjects in period 1
    		Octreotide capsules
    Started
    155
    Completed
    102
    Not completed
    53
         Consent withdrawn by subject
    5
         Treatment failure
    24
         Sponsor request
    1
         Adverse event
    21
         Lost to follow-up
    2
    Period 2
    Period 2 title
    Extension Treatment Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Octreotide capsules
    Arm description
    		 All patients
    Arm type
    		 Experimental

    Investigational medicinal product name
    Octreotide 20 mg capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Oral octreotide treatment was started at a dose of 40 mg/day (20 mg bid). Dose escalation was based on measurement of the patient’s IGF-1 levels and acromegaly-related symptoms. The dose was titrated on an individual basis, stepwise from 40 mg/day to 60 mg/day (40 mg in the morning, 20 mg in the evening) to a maximum of 80 mg/day (40 mg bid) until maximum hormonal suppression was achieved.

    Number of subjects in period 2 [1]
    		Octreotide capsules
    Started
    88
    Completed
    82
    Not completed
    6
         Consent withdrawn by subject
    2
         Treatment failure
    2
         Adverse event
    2
    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: ontinuation of treatment in the 6-month extension period was voluntary. Patients completing the Core Treatment Period might have chosen to not continue treatment in the extension period and might have discontinued the study. Therefore, the number of patients completing the Core Treatment Period is higher than the number of patients starting the Extension Treatment Period.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Core Treatment Period
    Reporting group description
    		 -

    Reporting group values
    		 Core Treatment Period Total
    Number of subjects
    		 155 155
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 127 127
        From 65-84 years
    		 28 28
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 54.2 ± 11.5 -
    Gender categorical
    Units: Subjects
        Female
    		 67 67
        Male
    		 88 88
    Subject analysis sets

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All patients enrolled who had received any amount of study drug and had at least one post-baseline assessment

    Subject analysis set title
    Modified intention-to-treat population
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All enrolled patients who received any amount of study drug and had at least one post-baseline assessment of insulin-like growth factor 1 (IGF-1) or growth hormone (GH)

    Subject analysis set title
    Extension intention-to-treat population
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All patients enrolled in the Extension Treatment Period

    Subject analysis set title
    Fixed dose population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Enrolled patients who received any amount of study drug, had at least one post-baseline IGF-1 or GH assessment, and had entered the Fixed Dose Phase of the Core Treatment Period

    Subject analysis sets values
    		 Safety population Modified intention-to-treat population Extension intention-to-treat population Fixed dose population
    Number of subjects
    155
    151
    88
    110
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    127
        From 65-84 years
    28
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    54.2 ± 11.5
    ±
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    67
        Male
    88

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Octreotide capsules
    Reporting group description
    		 All patients
    Reporting group title
    Octreotide capsules
    Reporting group description
    		 All patients

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All patients enrolled who had received any amount of study drug and had at least one post-baseline assessment

    Subject analysis set title
    Modified intention-to-treat population
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All enrolled patients who received any amount of study drug and had at least one post-baseline assessment of insulin-like growth factor 1 (IGF-1) or growth hormone (GH)

    Subject analysis set title
    Extension intention-to-treat population
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All patients enrolled in the Extension Treatment Period

    Subject analysis set title
    Fixed dose population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Enrolled patients who received any amount of study drug, had at least one post-baseline IGF-1 or GH assessment, and had entered the Fixed Dose Phase of the Core Treatment Period

    Primary: Percentage of responders at the end of the Core Treatment Period

    		 Close Top of page
    End point title
    		 Percentage of responders at the end of the Core Treatment Period [1]
    End point description
    A responder was defined as patient with a serum IGF-1 concentration of <1.3 times the upper limit of normal (ULN) (adjusted for age and gender) and a GH concentration <2.5 ng/mL. The GH concentration was the mean of 5 fasted GH serum concentrations collected at 30-minute intervals for 2 h, 2 to 4 h after octreotide administration. The IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.
    End point type
    Primary
    End point timeframe
    End of the Core Treatment Period (up to 7 months)
    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: This primary endpoint was analysed using descriptive statistics only. No inferential testing was applied. A p-value was not defined.
    End point values
    		 Octreotide capsules Modified intention-to-treat population
    Number of subjects analysed
    151
    151
    Units: percent
        number (confidence interval 95%)
    64.9 (58.4 to 74.2)
    64.9 (58.4 to 74.2)
    No statistical analyses for this end point

    Primary: Percentage of responders at the end of the Extension Treatment Period

    		 Close Top of page
    End point title
    		 Percentage of responders at the end of the Extension Treatment Period [2]
    End point description
    A responder was defined as patient with a serum IGF-1 concentration of <1.3 times the ULN (adjusted for age and gender) and a GH concentration <2.5 ng/mL. The GH concentration was the mean of 5 fasted GH serum concentrations collected at 30-minute intervals for 2 h, 2 to 4 h after octreotide administration. The IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.
    End point type
    Primary
    End point timeframe
    End of the Extension Treatment Period (up to 13 months)
    Notes
    [2] - 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: This primary endpoint was analysed using descriptive statistics only. No inferential testing was applied. A p-value was not defined.
    End point values
    		 Octreotide capsules Extension intention-to-treat population
    Number of subjects analysed
    88
    88
    Units: percent
        arithmetic mean (confidence interval 98%)
    78.4 (68.4 to 86.5)
    78.4 (68.4 to 86.5)
    No statistical analyses for this end point

    Secondary: Percentage of patients with specified IGF-1 and GH concentrations at baseline and at the end of the Core Treatment Period

    		 Close Top of page
    End point title
    		 Percentage of patients with specified IGF-1 and GH concentrations at baseline and at the end of the Core Treatment Period
    End point description
    Percentage of patients with the following serum IGF-1 and GH concentrations at baseline (BL) and at the end of the Core Treatment Period (CTP): IGF-1 <1.3 x ULN and GH <5.0 ng/mL; IGF-1 <1.3 x ULN and GH <1.0 ng/mL, IGF-1 ≤1 x ULN and GH < 5.0 ng/mL, IGF-1 ≤1 x ULN and GH <2.5 ng/mL, IGF-1 ≤1 x ULN and GH <1.0 ng/mL, IGF-1 <1.3 x ULN, IGF-1 ≤1 x ULN, GH <5.0 ng/mL, GH <2.5 ng/mL, GH <1.0 ng/mL, IGF-1 ≥1.3 x ULN and GH <2.5 ng/mL, IGF-1 <1.3 x ULN and GH ≥2.5 ng/mL, and IGF-1 ≥1.3 x ULN and GH ≥2.5 ng/mL. The GH concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 h, 2 to 4 h after octreotide administration. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.
    End point type
    Secondary
    End point timeframe
    Baseline (BL) and end of the Core Treatment Period (CTP): up to 7 months
    End point values
    		 Octreotide capsules
    Number of subjects analysed
    151
    Units: percent
    number (not applicable)
        IGF-1 <1.3 x ULN and GH <5 ng/mL: BL
    91.4
        IGF-1 <1.3 x ULN and GH <5 ng/mL: CTP
    65.6
        IGF-1 <1.3 x ULN and GH <1 ng/mL: BL
    62.9
        IGF-1 <1.3 x ULN and GH <1 ng/mL: CTP
    53
        IGF-1 ≤1 x ULN and GH <5 ng/mL: BL
    63.6
        IGF-1 ≤1 x ULN and GH <5 ng/mL: CTP
    35.8
        IGF-1 ≤1 x ULN and GH <2.5 ng/mL: BL
    61.6
        IGF-1 ≤1 x ULN and GH <2.5 ng/mL: CTP
    35.8
        IGF-1 ≤1 x ULN and GH <1 ng/mL: BL
    43
        IGF-1 ≤1 x ULN and GH <1 ng/mL: CTP
    31.8
        IGF-1 <1.3 x ULN: BL
    91.4
        IGF-1 <1.3 x ULN: CTP
    66.9
        IGF-1 ≤1 x ULN: BL
    63.6
        IGF-1 ≤1 x ULN: CTP
    37.1
        GH <5 ng/mL: BL
    100
        GH <5 ng/mL: CTP
    97.4
        GH <2.5 ng/mL: BL
    96
        GH <2.5 ng/mL: CTP
    94.7
        GH <1 ng/mL: BL
    66.2
        GH <1 ng/mL: CTP
    77.5
        IGF-1 ≥1.3 x ULN and GH <2.5 ng/mL: BL
    7.3
        IGF-1 ≥1.3 x ULN and GH <2.5 ng/mL: CTP
    29.8
        IGF-1 <1.3 x ULN and GH ≥2.5 ng/mL: BL
    2.6
        IGF-1 <1.3 x ULN and GH ≥2.5 ng/mL: CTP
    0.7
        IGF-1 ≥1.3 x ULN and GH ≥2.5 ng/mL: BL
    1.3
        IGF-1 ≥1.3 x ULN and GH ≥2.5 ng/mL: CTP
    2
    No statistical analyses for this end point

    Secondary: Maintenance of response during the Fixed Dose Phase of the Core Treatment Period

    		 Close Top of page
    End point title
    		 Maintenance of response during the Fixed Dose Phase of the Core Treatment Period
    End point description
    Maintenance of response during the Fixed Dose Phase (FDP) of the Core Treatment Period (CTP) was defined as the percentage of patients with an IGF-1 concentration <1.3 x ULN at the beginning of the Fixed Dose Phase of the Core Treatment Period and at the end of the Core Treatment Period. IGF-1 concentration was determined in serum samples taken at the same visits the GH concentration was assessed.
    End point type
    Secondary
    End point timeframe
    Beginning of the Fixed Dose Phase (FDP) of the Core Treatment Period (CTP) and end of the Core Treatment Period (CTP): up to 7 months
    End point values
    		 Octreotide capsules
    Number of subjects analysed
    110
    Units: percent
    number (not applicable)
        Beginning of the FDP of the CTP
    82.7
        End of the CTP
    80
    No statistical analyses for this end point

    Secondary: Percentage of patients with specified IGF-1 and GH concentrations at baseline and at the end of the Extension Treatment Period

    		 Close Top of page
    End point title
    		 Percentage of patients with specified IGF-1 and GH concentrations at baseline and at the end of the Extension Treatment Period
    End point description
    Percentage of patients with the following serum IGF-1 and GH concentrations at beginning (BETP) and at the end of the Extension Treatment Period (EETP): IGF-1 <1.3 x ULN and GH <5.0 ng/mL; IGF-1 <1.3 x ULN and GH <1.0 ng/mL, IGF-1 ≤1 x ULN and GH < 5.0 ng/mL, IGF-1 ≤1 x ULN and GH <2.5 ng/mL, IGF-1 ≤1 x ULN and GH <1.0 ng/mL, IGF-1 <1.3 x ULN, IGF-1 ≤1 x ULN, GH <5.0 ng/mL, GH <2.5 ng/mL, GH <1.0 ng/mL, IGF-1 ≥1.3 x ULN and GH <2.5 ng/mL, IGF-1 <1.3 x ULN and GH ≥2.5 ng/mL, and IGF-1 ≥1.3 x ULN and GH ≥2.5 ng/mL. The GH concentration was the mean of 5 fasted GH serum concentrations collected at 30 minute intervals for 2 h, 2 to 4 h after octreotide administration. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.
    End point type
    Secondary
    End point timeframe
    Baseline and end of the Extension Treatment Period (up to 6 months)
    End point values
    		 Octreotide capsules
    Number of subjects analysed
    88
    Units: percent
    number (not applicable)
        IGF-1 <1.3 x ULN and GH <5 ng/mL: BETP
    84.1
        IGF-1 <1.3 x ULN and GH <5 ng/mL: EETP
    79.5
        IGF-1 <1.3 x ULN and GH <1 ng/mL: BETP
    69.3
        IGF-1 <1.3 x ULN and GH <1 ng/mL: EETP
    68.2
        IGF-1 ≤1 x ULN and GH <5 ng/mL: BETP
    48.9
        IGF-1 ≤1 x ULN and GH <5 ng/mL: EETP
    50
        IGF-1 ≤1 x ULN and GH <2.5 ng/mL: BETP
    48.9
        IGF-1 ≤1 x ULN and GH <2.5 ng/mL: EETP
    50
        IGF-1 ≤1 x ULN and GH <1 ng/mL: BETP
    42
        IGF-1 ≤1 x ULN and GH <1 ng/mL: EETP
    44.3
        IGF-1 <1.3 x ULN: BETP
    84.1
        IGF-1 <1.3 x ULN: EETP
    79.5
        IGF-1 ≤1 x ULN: BETP
    48.9
        IGF-1 ≤1 x ULN: EETP
    50
        GH <5 ng/mL: BETP
    100
        GH <5 ng/mL: EETP
    97.7
        GH <2.5 ng/mL: BETP
    98.9
        GH <2.5 ng/mL: EETP
    95.5
        GH <1 ng/mL: BETP
    83
        GH <1 ng/mL: EETP
    83
        IGF-1 ≥1.3 x ULN and GH <2.5 ng/mL: BETP
    14.8
        IGF-1 ≥1.3 x ULN and GH <2.5 ng/mL: EETP
    17
        IGF-1 <1.3 x ULN and GH ≥2.5 ng/mL: BETP
    0
        IGF-1 <1.3 x ULN and GH ≥2.5 ng/mL: EETP
    1.1
        IGF-1 ≥1.3 x ULN and GH ≥2.5 ng/mL: BETP
    1.1
        IGF-1 ≥1.3 x ULN and GH ≥2.5 ng/mL: EETP
    3.4
    No statistical analyses for this end point

    Secondary: Maintenance of response during the Extension Treatment Period

    		 Close Top of page
    End point title
    		 Maintenance of response during the Extension Treatment Period
    End point description
    Maintenance of an IGF-1 response during the Extension Treatment Period was defined as the percentage of patients with IGF-1 concentration <1.3 x ULN at the beginning of the Extension Treatment Period and at the end of the Extension Treatment Period. IGF-1 concentration was determined in serum samples taken at the same visits GH concentration was assessed.
    End point type
    Secondary
    End point timeframe
    Beginning of the Extension Treatment Period and end of the Extension Treatment Period (up to 13 months)
    End point values
    		 Octreotide capsules
    Number of subjects analysed
    88
    Units: percent
    arithmetic mean (confidence interval 95%)
        Beginning of the FDP of the CTP
    87.8 (78.2 to 94.3)
    No statistical analyses for this end point

    Secondary: Percentage of patients with improved or maintained acromegaly symptoms at the end of the Extension Treatment Period

    		 Close Top of page
    End point title
    		 Percentage of patients with improved or maintained acromegaly symptoms at the end of the Extension Treatment Period
    End point description
    The severity (absent, mild, moderate, severe) of the 5 acromegaly symptoms headache, perspiration, asthenia, swelling of extremities, and joint pain was assessed at baseline and at the end of the Extension Treatment Period. The percentage of patients with improved or maintained (no change) acromegaly symptoms from baseline to the end of the Extension Treatment Period is reported.
    End point type
    Secondary
    End point timeframe
    Baseline and end of the Extension Treatment Period (up to 13 months)
    End point values
    		 Octreotide capsules
    Number of subjects analysed
    88
    Units: percent
    arithmetic mean (confidence interval 95%)
        Maintained
    27 (18.3 to 37.8)
        Improved
    57 (45.8 to 67.3)
    No statistical analyses for this end point

    Post-hoc: Percentage of patients with ≥1, 2, or 3 acromegaly symptoms at baseline and at the end of the Extension Treatment Period (EETP)

    		 Close Top of page
    End point title
    		 Percentage of patients with ≥1, 2, or 3 acromegaly symptoms at baseline and at the end of the Extension Treatment Period (EETP)
    End point description
    Percentage of patients who had ≥1, 2, or 3 of the 5 acromegaly symptoms (headaches, perspiration, asthenia, swelling of extremities, joint pain) of any severity (mild, moderate, severe). This was a post hoc analysis.
    End point type
    Post-hoc
    End point timeframe
    Baseline and end of the Extension Treatment Period (up to 13 months)
    End point values
    		 Octreotide capsules
    Number of subjects analysed
    88
    Units: percent
    number (not applicable)
        1 symptom, baseline
    78
        1 symptom, EETP
    65
        2 symptoms, baseline
    61
        2 symptoms, EETP
    43
        3 symptoms, baseline
    43
        3 symptoms, EETP
    25
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Core Treatment Period plus Extension Treatment Period (up to 13 months)
    Adverse event reporting additional description
    The total number of patients with AEs is greater than the 155 patients enrolled in the study because of the study’s dose-escalation design: patients might have experienced AEs at more than one dose level they received during the study
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14
    Reporting groups
    Reporting group title
    Octreotide 40 mg
    Reporting group description
    		 Patients receiving octreotide 40 mg/day (20 mg/bid) for up to 13 months

    Reporting group title
    Octreotide 60 mg
    Reporting group description
    		 Patients receiving octreotide 60 mg/day (40 mg in the morning and 20 mg in the evening) for up to 13 months

    Reporting group title
    Octreotide 80 mg
    Reporting group description
    		 Patients receiving octreotide 80 mg/day (40 mg/bid) for up to 13 months

    Serious adverse events
    		 Octreotide 40 mg Octreotide 60 mg Octreotide 80 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 155 (5.81%)
    7 / 91 (7.69%)
    8 / 58 (13.79%)
         number of deaths (all causes)
    1
    0
    1
         number of deaths resulting from adverse events
    1
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer recurrent
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    General disorders and administration site conditions
    Impaired healing
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Investigations
    Transaminases increased
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Bradycardia
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    2 / 155 (1.29%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Spleen disorder
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Melaena
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bile duct obstruction
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Chronic sinusitis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Corneal abscess
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex ophthalmic
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 155 (0.65%)
    0 / 91 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    0 / 155 (0.00%)
    1 / 91 (1.10%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 155 (0.00%)
    0 / 91 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Octreotide 40 mg Octreotide 60 mg Octreotide 80 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    103 / 155 (66.45%)
    51 / 91 (56.04%)
    31 / 58 (53.45%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 155 (3.87%)
    4 / 91 (4.40%)
    3 / 58 (5.17%)
         occurrences all number
    8
    4
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    44 / 155 (28.39%)
    18 / 91 (19.78%)
    20 / 58 (34.48%)
         occurrences all number
    46
    38
    64
    Dizziness
         subjects affected / exposed
    8 / 155 (5.16%)
    1 / 91 (1.10%)
    2 / 58 (3.45%)
         occurrences all number
    9
    1
    4
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    27 / 155 (17.42%)
    11 / 91 (12.09%)
    8 / 58 (13.79%)
         occurrences all number
    40
    17
    11
    Oedema peripheral
         subjects affected / exposed
    19 / 155 (12.26%)
    8 / 91 (8.79%)
    5 / 58 (8.62%)
         occurrences all number
    31
    10
    5
    Fatigue
         subjects affected / exposed
    6 / 155 (3.87%)
    1 / 91 (1.10%)
    2 / 58 (3.45%)
         occurrences all number
    8
    1
    2
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    30 / 155 (19.35%)
    14 / 91 (15.38%)
    6 / 58 (10.34%)
         occurrences all number
    35
    16
    10
    Diarrhoea
         subjects affected / exposed
    18 / 155 (11.61%)
    11 / 91 (12.09%)
    4 / 58 (6.90%)
         occurrences all number
    22
    15
    5
    Dyspepsia
         subjects affected / exposed
    11 / 155 (7.10%)
    2 / 91 (2.20%)
    1 / 58 (1.72%)
         occurrences all number
    15
    2
    1
    Abdominal pain upper
         subjects affected / exposed
    10 / 155 (6.45%)
    2 / 91 (2.20%)
    3 / 58 (5.17%)
         occurrences all number
    11
    3
    3
    Flatulence
         subjects affected / exposed
    10 / 155 (6.45%)
    1 / 91 (1.10%)
    2 / 58 (3.45%)
         occurrences all number
    10
    2
    3
    Abdominal pain
         subjects affected / exposed
    5 / 155 (3.23%)
    7 / 91 (7.69%)
    1 / 58 (1.72%)
         occurrences all number
    5
    8
    1
    Abdominal distension
         subjects affected / exposed
    7 / 155 (4.52%)
    4 / 91 (4.40%)
    1 / 58 (1.72%)
         occurrences all number
    8
    5
    1
    Vomiting
         subjects affected / exposed
    4 / 155 (2.58%)
    3 / 91 (3.30%)
    4 / 58 (6.90%)
         occurrences all number
    4
    3
    4
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    4 / 155 (2.58%)
    3 / 91 (3.30%)
    3 / 58 (5.17%)
         occurrences all number
    4
    3
    3
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    23 / 155 (14.84%)
    9 / 91 (9.89%)
    6 / 58 (10.34%)
         occurrences all number
    44
    17
    7
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    25 / 155 (16.13%)
    20 / 91 (21.98%)
    11 / 58 (18.97%)
         occurrences all number
    48
    28
    21
    Myalgia
         subjects affected / exposed
    2 / 155 (1.29%)
    2 / 91 (2.20%)
    3 / 58 (5.17%)
         occurrences all number
    2
    2
    3
    Neck pain
         subjects affected / exposed
    3 / 155 (1.94%)
    1 / 91 (1.10%)
    3 / 58 (5.17%)
         occurrences all number
    3
    1
    6
    Back pain
         subjects affected / exposed
    5 / 155 (3.23%)
    3 / 91 (3.30%)
    1 / 58 (1.72%)
         occurrences all number
    7
    3
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    5 / 155 (3.23%)
    4 / 91 (4.40%)
    5 / 58 (8.62%)
         occurrences all number
    10
    4
    6
    Influenza
         subjects affected / exposed
    6 / 155 (3.87%)
    4 / 91 (4.40%)
    3 / 58 (5.17%)
         occurrences all number
    6
    4
    4
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 155 (3.87%)
    2 / 91 (2.20%)
    3 / 58 (5.17%)
         occurrences all number
    6
    2
    4
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    3 / 155 (1.94%)
    2 / 91 (2.20%)
    3 / 58 (5.17%)
         occurrences all number
    3
    2
    5

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Aug 2011
    Amendment 1 specified pituitary MRI versus brain MRI; clarified the patient inclusion age range of 18 to 75 years; added assessments of anti-octreotide antibodies, and safety assessments of insulin, TSH, free T4, vitamin B12, and HbA1c; modified a secondary efficacy endpoint by adding an analysis of the proportion of patients with a mean GH concentration of <1.0 ng/mL; added a new secondary efficacy endpoint of proportion of patients with both normalized IGF-1 levels (adjusted for age) and mean integrated GH over 2 h <2.5 ng/mL; clarified dose escalation; clarified use of prohibited concomitant medications; and clarified the Schedule of Activities table by including more Information.
    22 May 2012
    Amendment 2 added a 6-month Extension Treatment Period as an option to eligible patients and specified eligibility criteria; allowed for rescreening of patients; clarified the timing of study visits so that the Dose Escalation Phase and the Fixed Dose Phase of the Core Treatment Period had a total duration of at least 7 months; specified that the primary efficacy endpoint and analysis pertained to the Core Treatment Period; specified that there were 2 separate analyses for the Core Treatment Period and the Extension Treatment Period; clarified that serum pregnancy tests were performed at all study visits; added microscopic observations to the screening urinalysis; revised the octreotide antibody sampling time points to allow for the evaluation of the effect of octreotide antibodies on the PK profile of MYCAPSSA; added an exploratory efficacy endpoint for MYCAPSSA PK; added an exploratory efficacy endpoint for octreotide antibodies; clarified study visit procedures to be performed in the event of early discontinuation; specified a visit window for the Follow-Up Period and revised study procedures at the Follow-Up visit; added 5 supplemental questions to the TSQM; and revised the Schedule of Activities to include the 6-month Extension Treatment Period and modified the table footnotes accordingly.
    07 Dec 2012
    Amendment 3 permitted the use of serum GH samples that were stored after analysis to complete a full set of visit TA1, TA2, TA4, and TB6/EOT octreotide antibody sample analysis for each patient completing the study; added the inclusion of octreotide antibody analysis at time points TA1, TA2, TA4 and TB6/EOT; allowed stored serum GH samples to be used for octreotide PK analysis for the PK sub-study; and introduced a correction to the timing of diary card completion.
    06 Dec 2013
    Amendment 4 included modifications to study endpoints and response categories to allow more educated and informative data interpretation; added the Food Intake and Oral Octreolin Administration Questionnaire as a study procedure to assess the timing of dose administration and relation to food and beverage consumption; and introduced updates to the contact information for the sponsor and CROs.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 23:49:16 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA