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   43974   clinical trials with a EudraCT protocol, of which   7311   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A 52-week, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Relamorelin in Patients with Diabetic Gastroparesis

    Summary
    EudraCT number
    2017-002144-33
    Trial protocol
    GB   HU   FR   BE   BG   DK   AT   LV   ES   IT  
    Global end of trial date
    05 Nov 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Oct 2021
    First version publication date
    20 Oct 2021
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    RLM-MD-04
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03383146
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Allergan
    Sponsor organisation address
    1st Floor, Marlow International, The Parkway, Marlow Buckinghamshire, United Kingdom, SL7 1YL
    Public contact
    Therapeutic Area, Head, Allergan, 001 714-246-4500, IR-CTRegistration@Allergan.com
    Scientific contact
    Therapeutic Area, Head, Allergan, 001 714-246-4500, IR-CTRegistration@Allergan.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
    05 Nov 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Nov 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of the study was to compare the efficacy of relamorelin with that of placebo in participants with diabetic gastroparesis (DG) with respect to the core signs and symptoms of diabetic gastroparesis.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Feb 2018
    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
    Bulgaria: 1
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Latvia: 6
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Argentina: 19
    Country: Number of subjects enrolled
    Brazil: 16
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    Colombia: 11
    Country: Number of subjects enrolled
    India: 1
    Country: Number of subjects enrolled
    Malaysia: 1
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    Philippines: 1
    Country: Number of subjects enrolled
    Russian Federation: 1
    Country: Number of subjects enrolled
    South Africa: 16
    Country: Number of subjects enrolled
    Korea, Republic of: 1
    Country: Number of subjects enrolled
    Ukraine: 14
    Country: Number of subjects enrolled
    United States: 331
    Worldwide total number of subjects
    450
    EEA total number of subjects
    13
    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)
    316
    From 65 to 84 years
    133
    85 years and over
    1

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Participants who completed the placebo run-in of relamorelin studies: RLM-MD-01 [NCT03285308] and RLM-MD-02 [NCT03426345] were eligible to rollover to this study. De novo (New) participants, who had not participated in the previous studies, were also eligible for enrollment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Placebo injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo-matching relamorelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo injected subcutaneously twice daily.

    Arm title
    Relamorelin 10 μg
    Arm description
    Relamorelin 10 micrograms (μg) injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.
    Arm type
    Experimental

    Investigational medicinal product name
    Relamorelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Relamorelin 10 micrograms (μg) injected subcutaneously twice daily.

    Number of subjects in period 1
    Placebo Relamorelin 10 μg
    Started
    148
    302
    Safety Population
    145
    299
    Run-in Period
    91
    207
    Completed
    63
    118
    Not completed
    85
    184
         Physician decision
    -
    1
         Screen Failure
    1
    -
         Adverse Event
    6
    18
         Protocol Deviation
    1
    8
         Death
    -
    2
         Withdrawal by Subject
    20
    36
         Study Terminated by the Sponsor
    48
    95
         Lost to follow-up
    5
    15
         Reason not Specified
    4
    6
         Lack of efficacy
    -
    3

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.

    Reporting group title
    Relamorelin 10 μg
    Reporting group description
    Relamorelin 10 micrograms (μg) injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.

    Reporting group values
    Placebo Relamorelin 10 μg Total
    Number of subjects
    148 302 450
    Age categorical
    Units: Subjects
        Adults (<65 years)
    107 209 316
        From >= 65 years
    41 93 134
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    57.0 ( 12.37 ) 57.9 ( 11.57 ) -
    Sex: Female, Male
    Units: participants
        Female
    102 224 326
        Male
    46 78 124
    Race
    Units: Subjects
        American Indian or Alaska Native
    7 11 18
        Asian
    0 9 9
        Native Hawaiian or Other Pacific Islander
    1 0 1
        Black or African American
    27 53 80
        White
    109 218 327
        More than one race
    4 11 15
        Unknown or Not Reported
    0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    50 82 132
        Not Hispanic or Latino
    98 220 318
        Unknown or Not Reported
    0 0 0

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.

    Reporting group title
    Relamorelin 10 μg
    Reporting group description
    Relamorelin 10 micrograms (μg) injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.

    Primary: Change from Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS)

    Close Top of page
    End point title
    Change from Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS) [1]
    End point description
    Participants assessed the severity of diabetic gastroparesis symptoms daily using the Diabetic Gastroparesis Symptom Severity Diary (DGSSD), recorded in an electronic diary (e-diary). The DGSSS was derived as the sum of the weekly averages of the 4 DGSSD items: nausea, abdominal pain, postprandial fullness and bloating. Each symptom was scored using an 11-point ordinal scale where: 0=no or not at all uncomfortable to 10=worst possible or most uncomfortable for a total possible DGSSS of 0 (best) to 40 (worst). A negative change from Baseline indicates improvement. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period of the previous study or the run-in period of this study for new participants. Modified-intent-to-treat (mITT) Population included all randomised participants with ≥1 postbaseline assessment of DGSSD. 'n' indicates number analysed is the number of participants with data available at the given time-point.
    End point type
    Primary
    End point timeframe
    Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02 for rollover participants or Day -14 to Day -1 for new participants) to Week 12 of this study
    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 analyses are reported for this endpoint.
    End point values
    Placebo Relamorelin 10 μg
    Number of subjects analysed
    147
    295
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n=147, 295)
    20.3 ( 6.70 )
    19.7 ( 6.39 )
        Change from Baseline to Week 12 (n=133, 247)
    -7.1 ( 8.82 )
    -6.5 ( 7.80 )
    No statistical analyses for this end point

    Primary: Change from Baseline to Week 52 in the Weekly Average DGSSS

    Close Top of page
    End point title
    Change from Baseline to Week 52 in the Weekly Average DGSSS [2]
    End point description
    Participants assessed the severity of diabetic gastroparesis symptoms daily using the DGSSD, recorded in an electronic diary (e-diary). The DGSSS was derived as the sum of the weekly averages of the 4 DGSSD items: nausea, abdominal pain, postprandial fullness and bloating. Each symptom was scored using an 11-point ordinal scale where: 0=no or not at all uncomfortable to 10=worst possible or most uncomfortable for a total possible DGSSS of 0 (best) to 40 (worst). The average weekly scores at Week 52 were the average of the DGSSS scores from Week 49 to Week 52. A negative change from Baseline indicates improvement. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period of the previous study or the run-in period of this study for new participants. mITT Population included all randomised participants with ≥1 postbaseline assessment of DGSSD. 'n' indicates number analysed is the number of participants with data available at the given time-point.
    End point type
    Primary
    End point timeframe
    Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02 for rollover participants or Day -14 to Day -1 for new participants) to Week 52 of this study
    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: No statistical analyses are reported for this endpoint.
    End point values
    Placebo Relamorelin 10 μg
    Number of subjects analysed
    147
    295
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n=147, 295)
    20.3 ( 6.70 )
    19.7 ( 6.39 )
        Change from Baseline to Week 52 (n=65, 129)
    -10.7 ( 8.93 )
    -8.6 ( 8.92 )
    No statistical analyses for this end point

    Primary: Number of Participants who Experienced One or More Treatment-Emergent Adverse Events (TEAE)

    Close Top of page
    End point title
    Number of Participants who Experienced One or More Treatment-Emergent Adverse Events (TEAE) [3]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is an AE that begins or worsens after receiving study drug. Safety Population included all participants who received ≥1 administration of study treatment.
    End point type
    Primary
    End point timeframe
    First dose of study drug to within 30 days of the last dose of study drug (Up to approximately 56 weeks)
    Notes
    [3] - 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 analyses are reported for this endpoint.
    End point values
    Placebo Relamorelin 10 μg
    Number of subjects analysed
    145
    299
    Units: participants
    105
    221
    No statistical analyses for this end point

    Primary: Number of Participants with Potential Clinically Significant (PCS) Clinical Laboratory Results

    Close Top of page
    End point title
    Number of Participants with Potential Clinically Significant (PCS) Clinical Laboratory Results [4]
    End point description
    Clinical Laboratory tests included Hematology, Chemistry and Urinalysis tests. The investigator determined if the results were clinically significant. Only those categories where at least 1 participant had a non-PCS value at Baseline and met the PCS criterion at least once during postbaseline are reported. Safety Population included all participants who received ≥1 administration of study treatment. 'n' indicates number analysed is the number of participants with non-PCS Baseline values and at least one post-baseline assessment. Upper limit of normal value (ULN), lower limit of normal value (LLN), gram (g), liter(L), femtoliter (fL), millimoles(mmol/L), micromoles(μmol/L), absolute cell count (ACC), red blood cell (RBC), white blood cell (WBC), alanine aminotransferase (ALT), serum glutamate-pyruvate transaminase (SGPT), aspartate aminotransferase, serum glutamic-oxaloacetic transaminase (SGOT) unit (U), fasting (F), glycohemoglobin A1C (HbA1c).
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    Notes
    [4] - 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 analyses are reported for this endpoint.
    End point values
    Placebo Relamorelin 10 μg
    Number of subjects analysed
    145
    299
    Units: participants
        Hematocrit (RATIO): >1.1×ULN (n=139, 289)
    0
    1
        Hematocrit (RATIO): <0.9×LLN (n=139, 289)
    5
    14
        Hemoglobin (g)/L): <0.9×LLN (n=137, 288)
    10
    20
        Lymphocytes ACC(10^9/(L): >1.5×ULN (n=141, 287)
    1
    5
        Lymphocytes ACC (10^9/L): <0.8×LLN (n=141, 287)
    2
    9
        Mean Corpuscular Volume (fL):>1.1×ULN (n=140, 284)
    2
    2
        Neutrophils ACC (10^9/L): >1.5×ULN (n=143, 288)
    2
    0
        Neutrophils ACC (10^9/L): <0.8×LLN (n= 143, 288)
    7
    3
        RBC (10^12/L):<0.9×LLN (n=141, 290)
    2
    10
        WBC (10^9/L): <0.7×LLN (n=144, 291)
    2
    0
        ALT (SGPT) (U)/L): ≥3.0×ULN (n=144, 291)
    0
    6
        Albumin (g/L): <0.9×LLN (n=143, 292)
    0
    1
        Alkaline Phosphatase (U/L): ≥3.0×ULN (n=144, 292)
    0
    1
        AST (SGOT) (U/L): ≥3.0×ULN (n=144, 291)
    2
    3
        Bicarbonate (HCO3) (mmol)/L):>1.1×ULN (n=138, 290)
    3
    2
        Bicarbonate (HCO3) (mmol)/L):>1.1×LLN (n=138, 290)
    3
    2
        Bicarbonate (HCO3) (mmol)/L):<0.9×LLN (n=138, 290)
    6
    6
        Bilirubin, Total (umol/L): >1.5×ULN (n=144, 292)
    0
    1
        Blood Urea Nitrogen (mmol/L):>1.2×ULN (n=125, 272)
    14
    27
        Calcium (mmol/L): >1.1×ULN (n=144, 292)
    0
    1
        Chloride (mmol/L): <0.9×LLN (n=144, 292)
    1
    1
        Cholesterol, Total, F(mmol/L):>1.6×ULN(n=142, 284)
    2
    5
        Creatinine (umol/L): >1.3×ULN (n=134, 275)
    15
    20
        Glucose-Chemistry, F(mmol/L):>2.5×ULN (n=132, 269)
    22
    52
        Glucose-Chemistry, F(mmol/L):<0.9×LLN (n=132, 269)
    4
    14
        HbA1C: Increase of ≥0.5% (n=144, 292)
    95
    247
        HbA1C: Increase of ≥1% (n=144, 292)
    94
    246
        Phosphorus (mmol/L): >1.1×ULN (n=142, 287)
    13
    5
        Phosphorus (mmol/L): <0.9×LLN (n=142, 287)
    1
    4
        Potassium (mmol/L): <0.9×LLN (n=144, 292)
    1
    0
        Protein, Total (g)/L): >1.1×ULN (n=143, 291)
    1
    0
        Triglycerides, F (mmol/L): ≥3.0×ULN (n=140, 280)
    8
    9
        Uric Acid (Urate) (umol/L): >1.1×ULN (n=114, 233)
    17
    37
        Uric Acid (Urate) (umol/L): <0.9×LLN (n=114, 233)
    1
    9
    No statistical analyses for this end point

    Primary: Number of Participants with Clinically Meaningful Trends for Vital Signs

    Close Top of page
    End point title
    Number of Participants with Clinically Meaningful Trends for Vital Signs [5]
    End point description
    Vital Signs included assessments of heart rate, respiratory rate, systolic and diastolic blood pressure, and body temperature. The investigator determined if the abnormal results were clinically significant. Safety Population included all participants who received ≥1 administration of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    Notes
    [5] - 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 analyses are reported for this endpoint.
    End point values
    Placebo Relamorelin 10 μg
    Number of subjects analysed
    145
    299
    Units: participants
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants with Clinically Significant Abnormal Electrocardiogram (ECG) Results

    Close Top of page
    End point title
    Number of Participants with Clinically Significant Abnormal Electrocardiogram (ECG) Results [6]
    End point description
    A standard 12-lead ECG was performed. The investigator determined if the abnormal results were clinically significant. Safety Population included all participants who received ≥1 administration of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    Notes
    [6] - 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 analyses are reported for this endpoint.
    End point values
    Placebo Relamorelin 10 μg
    Number of subjects analysed
    145
    299
    Units: participants
    2
    2
    No statistical analyses for this end point

    Primary: Number of Participants with Anti-relamorelin Antibody Testing Results by Visit

    Close Top of page
    End point title
    Number of Participants with Anti-relamorelin Antibody Testing Results by Visit [7] [8]
    End point description
    A blood sample was collected that was sent to a laboratory for an anti-relamorelin antibody screening test. A positive screening test was confirmed by an immunodepletion assay. The number of participants in each of the following categories are reported: Negative Screening Test, Positive Screening Test, Negative Confirmatory Test, and Positive Confirmatory Test at each time point. Safety Population included all participants who received ≥1 administration of double-blind study treatment (N=299 in the Relamorelin 10 μg arm). Anti-relamorelin antibody testing was only done for those participants who received treatment with relamorelin. 'n' indicates number analysed is the number of participants with data available at the given timepoint. Due to a laboratory issue not all positive screening tests were confirmed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), Day 84, Day 364, and End of Treatment (Up to Day 364)
    Notes
    [7] - 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 analyses are reported for this endpoint.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all Baseline arms are applicable to this endpoint.
    End point values
    Relamorelin 10 μg
    Number of subjects analysed
    299
    Units: participants
        Screening Test (Baseline) Negative (n=166)
    127
        Screening Test (Baseline) Positive (n=166)
    39
        Confirmatory Test (Baseline) Negative (n=5)
    5
        Confirmatory Test (Baseline) Positive (n=5)
    0
        Screening Test (Day 84) Negative (n=96)
    73
        Screening Test (Day 84) Positive (n=96)
    23
        Confirmatory Test (Day 84) Negative (n=7)
    6
        Confirmatory Test (Day 84) Positive (n=7)
    1
        Screening Test (Day 364) Negative (n=14)
    10
        Screening Test (Day 364) Positive (n=14)
    4
        Confirmatory Test (Day 364) Negative (n=0)
    0
        Confirmatory Test (Day 364) Positive (n=0)
    0
        Screening Test (End of Treatment) Negative (n=26)
    20
        Screening Test (End of Treatment) Positive (n=26)
    6
        Confirmatory Test (EOT) Negative (n=1)
    1
        Confirmatory Test (EOT) Positive (n=1)
    0
        Screening Test (Unscheduled) Negative (n=3)
    2
        Screening Test (Unscheduled) Positive (n=3)
    1
        Confirmatory Test (Unscheduled) Negative (n=1)
    1
        Confirmatory Test (Unscheduled) Positive (n=1)
    0
    No statistical analyses for this end point

    Primary: Number of Participants with a ≥1% Increase in Glycosylated Hemoglobin A1c (HbA1c)

    Close Top of page
    End point title
    Number of Participants with a ≥1% Increase in Glycosylated Hemoglobin A1c (HbA1c) [9]
    End point description
    HbA1c is also known as glycosylated hemoglobin. It is the concentration of glucose bound to hemoglobin as a percentage of the absolute maximum that can be bound. Safety Population included all participants who received ≥1 administration of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    Notes
    [9] - 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 analyses are reported for this endpoint.
    End point values
    Placebo Relamorelin 10 μg
    Number of subjects analysed
    145
    299
    Units: participants
    94
    246
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    First dose of study drug to within 30 days of the last dose of study drug (Up to approximately 56 weeks)
    Adverse event reporting additional description
    All-Cause Mortality included all randomised participants. Adverse Events: Safety Population included all participants who received ≥1 administration of study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Relamorelin 10 μg
    Reporting group description
    Relamorelin 10 μg injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.

    Reporting group title
    Placebo
    Reporting group description
    Placebo injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in.

    Serious adverse events
    Relamorelin 10 μg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 299 (14.38%)
    21 / 145 (14.48%)
         number of deaths (all causes)
    2
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasmacytoma
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Physical deconditioning
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    3 / 299 (1.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood glucose decreased
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glomerular filtration rate decreased
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 299 (1.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Animal bite
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery occlusion
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gastroparesis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureterolithiasis
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 299 (0.33%)
    2 / 145 (1.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metapneumovirus infection
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 299 (0.33%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    2 / 299 (0.67%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 299 (0.33%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 299 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Relamorelin 10 μg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    82 / 299 (27.42%)
    37 / 145 (25.52%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    15 / 299 (5.02%)
    7 / 145 (4.83%)
         occurrences all number
    16
    7
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    21 / 299 (7.02%)
    14 / 145 (9.66%)
         occurrences all number
    24
    14
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    18 / 299 (6.02%)
    11 / 145 (7.59%)
         occurrences all number
    20
    13
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    28 / 299 (9.36%)
    9 / 145 (6.21%)
         occurrences all number
    29
    9
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    15 / 299 (5.02%)
    8 / 145 (5.52%)
         occurrences all number
    21
    10

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Dec 2017
    The following changes were implemented with Amendment 1: -Added Screening and Run-in Periods to the protocol to allow participants to enter the study as de novo participants -Supplemented and revised the study schematic -Revised and supplemented the objectives and endpoints -Revised the number of participants and the description of the study population -Updated the Schedule of Activities (SoA) to add columns for Screening and Run-in, renumbered visits, and updated the footnotes -Deleted endpoint definitions -Revised the clinical hypotheses to present 2 new hypotheses in place of the original 4 hypotheses -Revised the number of participants -Updated the inclusion and exclusion criteria in to allow for participants who enrolled directly into RLM-MD-04; added 2 additional exclusion criteria -Updated the rational for the inclusion and exclusion criteria -Updated treatments administered -Updated treatment compliance -Updated concomitant therapy to alert the investigator that concomitant therapies should be held stable during the study, and to insert an exception to the prohibition for opioid use -Updated rescue medicine -Updated treatment after the end of the study -Updated temporary discontinuation -Updated study assessments and procedures -Updated primary efficacy assessments -Deleted secondary efficacy assessments -Added 2 new sections to include participants Global Impression of Status (PGIS-DG), and Patient Global Impression of Change (PGIC-DG).
    20 Dec 2017
    -Added treatment continuation -Revised time period and frequency for collecting adverse event (AE) and serious adverse event (SAE) information -Updated major adverse cardiovascular events -Updated treatment of overdose -Updated physical examination -Updated self-monitoring of blood glucose -added resource utilization assessment -Updated analysis populations -Updated statistical analyses -Updated efficacy analyses -Updated key endpoints -Updated missing data -Updated other screening tests -Updated tabular summary.
    29 Mar 2018
    The following changes were implemented with Amendment 2: -Updated SoA footnote (b) to indicate the early termination visit was performed as soon as possible after the decision has been made -Updated SoA (f) footnote to include evaluation of injection sites -Updated SoA footnote (j) to clarify the details of urine drug screen results -Updated SoA footnote (l) to indicate pregnancy testing can be performed if required by local regulations -Updated the SoA to add a new footnote (u) to inspect injection sites for clinically significant reactions -Revised inclusion criterion to remove the treatment requirement “for at least 3 months” for participants being treated with medications for diabetes mellitus type I (T1DM) or diabetes mellitus type II (T2DM) -Revised inclusion criterion to remove the upper limit for body mass index (BMI) -Revised exclusion criterion (History of intestinal malabsorption) for clarification that celiac disease even if well-controlled on gluten-free diet is exclusionary, and to add history of non-celiac gluten sensitivity as exclusionary -Revised exclusion criterion to remove functional dyspepsia -Deleted exclusion criterion which addresses anemia; in its place added exclusion criterion for gastric or duodenal ulcer within 3 months of screening -Revised exclusion criterion to reduce history of malignancy from 5 to 3 years -Revised exclusion criterion to shorten the exclusion period for promotility agents from 2 weeks to 10 days -Revised exclusion criterion which addresses positive drug screen results -Revised exclusion criterion to extend the exclusion for use of glucagon-like peptide-1 (GLP-1) agonists to 6 weeks, and remove pramlintide -Revised exclusion criterion to remove the allowance for gluten-free crackers -Added exclusion criterion for functional dyspepsia diagnosed before the diagnosis of diabetes mellitus.
    29 Mar 2018
    -Revised screen failures to disallow rescreening after greater than 6 months -Shortened the wash-out period for pro-motility agents, anticholinergics, anti-emetics, amylin analogue, and opioids from 2 weeks to 10 days; to extend the exclusion for use of GLP-1 agonists from 2 to 6 weeks prior to the start of the Run-in Period -Revised withdrawal from the study to indicate the early termination visit was performed as soon as possible after the decision to discontinue was made -Amended study assessments and procedures to increase the maximum amount of blood collected from 73.0 mL to 74.5 mL -Revised the time period for AE/SAE Collection to include “until 30 days after” the final visit -Amended the major adverse cardiovascular events (MACE) text for clarity and to describe the planned adjudication process -Amended physical examinations to add text about injection site inspection -Added anti-relamorelin antibodies test to other laboratory assessments -Revised the contraception guidance and added recommendations for acceptable birth control methods.
    29 Apr 2019
    The following changes were implemented with Amendment 3: -Replaced “Potential Hy’s Law” with “Hy’s Law” -Removed responder endpoints from list of key endpoints -Updated key objectives -Addition of other objectives and corresponding “Other Endpoints’’ -Schematic updated to show screening starting at Week -6 instead of Week -4 -Increased number of screening participants from 4000 to 5000 -Added requirements for “de novo” participants to have had a history of nausea and/or at most a single episode of vomiting in 2 weeks prior to screening added at screening Visit (Visit -2) -Deleted requirement for BMI -Increased number of sites from 400 to 700 -Deleted criterion for BMI > 18.5 kg/m2 -Beginning of Screening Period changed from Day -28 to Day -42; changed from “Up to 14 Days” to “Up to 28 Days” -Statement added to footnote (a) that results from assessments done at screening that might result in exclusion from the study are to be obtained prior to the endoscopy if done at the start of the Run-in Period -Added electrocardiogram (ECG) assessment at Visit 2 -Modified footnote (j) referencing to specify certain prescribed drugs (ie, barbiturates, benzodiazepines, amphetamines, but not opioids and cannabinoids) should not be exclusionary -Footnote “k” added for fasting glucose to be serum for all visits except Visits 4 and 6 (plasma) -Modified hypotheses -Changed requirement for delayed gastric emptying breath test (GEBT) from occurring at Screening to occurring during the Run-in Period -Modified inclusion criteria to add option to use upper GI series with contrast to document absence of obstructing lesion; revised time of performance from some time prior to Screening to some time prior to the Run-in Period -Section added for 2 new exclusion criteria applicable to both sets of participants including specific ECG results, allergy/hypersensitivity to study treatment.
    29 Apr 2019
    -Amended exclusion criteria to allow a participant with a positive urine drug screen at Screening to continue in the study while confirmatory testing is done on an aliquot of the original sample -Added reference to screen failures -Added exclusion criteria (hypersensitivity to study treatments and their excipients) and (ECG results obtained at baseline that would exclude a participant) -Added option for the sponsor to permit a participant with a positive urine drug screen at Screening to continue in the Screening Period while confirmatory urine drug screen testing by a more specific method is carried on an aliquot of the original sample -Clarified that the first dose of study treatment is to be administered within approximately 30 minutes before the morning meal and the second daily dose is to be administered approximately 30 minutes before the evening meal -Deleted option for investigator to contact sponsor if the participant could not inject study treatment into abdomen -Unblinding procedures modified; requirement of investigator to notify sponsor prior to unblinding modified to encouraging the investigator to notify the sponsor prior to unblinding, but requiring notification within 24 hours after breaking the blind -Sodium-glucose co-transporter-1 (SLGT-1) added to same rules for sodium-glucose co-transporter-2 (SGLT-2), Addition of details to the requirement of prohibiting SGLT-1 and SGLT-2 inhibitors -Amended information regarding SGLT-2 inhibitors as noted above and by adding SLGT-1 to same drug class/treatment as SGLT-2, rearranged rows by washout period, added tramadol as an example of opioid.
    29 Apr 2019
    -Added washout requirements for de novo participants -pro-motility agents, anticholinergics, anti-emetics, amyline analogue, 5 hydroxy tryptamine 4 (5HT4) agonists, and glucagon-like peptide-1 -Updated description of antiemetics -Added row for 5HT4 agonists -Amended washout period for opioids from “10 days prior to the start of the Run-in Period” to Not applicable since use of opioids is not allowed and referenced exclusion criteria -Specified that the day prior to and day of clinic visits are “during the Treatment Period” -Deleted antihistamines as an example of an anti-emetic drug -Revised to require investigator to contact (i.e., “should contact) sponsor if participant requires anti-emetic more than 1 day/week or once weekly repeatedly instead of making it optional for investigator to contact (i.e., “should consider contacting) -Deleted “non-compliance with study treatment” as a criterion -Additional criteria added for when the investigator should contact the sponsor -Added statement detailing when participants would be reporting their symptoms in the DGSSD -Deleted description on vomiting frequency and how vomiting was calculated -Changed title from “Other Patient-reported Outcomes (PRO) Assessments – Exploratory Endpoints to “Additional Assessments’’ -Added a subsection (i.e., Section 9.1.2.1) for description and calculation of vomiting frequency and renumbered all subsequent subsections accordingly -Specified that medical occurrences that begin before the start of study treatment but after obtaining informed consent was recorded in the AE section of the eCRF and was considered pretreatment AEs (instead of being recorded on the Medical History/Current Medical Conditions section of the eCRF) -Clarified reporting procedures for Hy’s Law cases -Added the phrase “Inadequate Control of Diabetes” to section title -Specified 10 μg twice a day (BID) or 20 μg/day as the maximum recommended dose.
    29 Apr 2019
    -Deleted statement referencing a dose of greater than 150 μg BID to be considered an overdose -Specified that the mITT Population is a subset of all randomised participants -Replaced Responder analysis with Change from Baseline (CFB) mixed model for repeated measures (MMRM) methodology and description -Deleted CFB ANCOVA methodology and description -Updated to only include CFB to Week 12 in weekly DGSSS and CFB to Week 52 in weekly average DGSSS -Deleted original text in section Section 10.3.2.2 Missing Data and replaced with reference to statistical analysis plan (SAP) -Added statement that data analyses for additional endpoints was specified in the SAP -Deleted language that PRO and HEOR measures was presented separately from CSR -Replaced the “Non-applicable” statement with a description of a DSMB process that was used to review interim safety data -Footnote added for fasting blood glucose to be serum at all visits except for Visits 4 & 6 -Headings added for subsections -Statement added that written documentation was obtained in accordance with relevant country and local privacy requirements -Revised from requirement of investigator retaining records for 15 years after study completion to retaining “as stated in the clinical trial agreement” -Added statement that the results of the study may be published or presented at scientific meetings -Updated procedures for reporting adverse events of special interest (AESIs) -Identified specific AESIs -Specified that DG symptoms were captured in the DGSSS and not the CRF -Moved acceptable methods of contraception from text to table -Deleted footnote “b” regarding hormonal contraception’s susceptible interactions with study intervention -Female participants who become pregnant –Deleted text that an elective termination is an AE or SAE; provided examples and details for abnormal pregnancy outcomes, including genetic abnormalities -Removed criteria for noncompliance -Changed trial length from 52 to 54 weeks.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    05 Nov 2020
    The study was prematurely terminated on 05 November 2020 as the sponsor decided not to develop the investigational product further. The study termination was not due to any safety concerns. As a result, only descriptive primary and secondary efficacy analyses and selected key safety analyses were conducted.
    -

    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA