A Safety and Efficacy Study of Relamorelin in Diabetic Ga... | NCT03383146

NCT03383146

ID	Type	Description	Link
2017-002144-33	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	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.	Drug: Placebo
Relamorelin 10 μg	Experimental	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.	Drug: Relamorelin

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo injected subcutaneously twice daily.	Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS)	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.	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
Change From Baseline to Week 52 in the Weekly Average DGSSS	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.	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
Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAE)	An adverse event (AE) is any untoward medical occurrence in a patient 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Two different groups of participants may enter into the study:

Rollover Participants

Participants who were not randomization-eligible at the end of the Run-in Period of lead-in studies RLM-MD-01 (NCT03285308) or RLM-MD-02 (NCT03426345) are eligible to be randomized in the study if all of the following criteria apply:

•In the lead-in studies, participants must have met all screening visit and Run-in Period criteria for randomization into the Treatment Period (including compliance with dosing, entry of diary data into the Diabetic Gastroparesis Symptom Severity Diary (DGSSD)) except that:
- They had zero vomiting episodes and an average daily Diabetic Gastroparesis Symptom Severity Score (DGSSS) of ≥12 at the end of the lead-in study Run-in Period, as reported using the electronic hand-held device; OR
- They had vomiting episodes and an average daily DGSSS of ≥12 but <16 at the end of the lead-in study Run-in Period, as reported using the electronic hand-held device
De Novo Participants
- Type 1 Diabetes Mellitus (T1DM) or Type 2 Diabetes Mellitus (T2DM) of at least 5 years' duration, with controlled and stable blood glucose levels and hemoglobin A1c (HBA1c) ≤11%
- DG defined as at least a 3-month history prior to Screening of symptoms (one of which must be nausea) on an ongoing basis that are suggestive of gastroparesis (GP) (e.g., nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety)
- Compliance with the entry of data into the hand-held electronic device during the Run-in Period
- Compliance with administration of subcutaneous (SC) twice daily injections during the Run-in Period
- The average of the daily DGSSS from the 2-week, Run-in Period must be ≥12

Exclusion Criteria:

Both Rollover and De Novo Participants

•Participants with a known allergy or hypersensitivity to the study treatments and their excipients (i.e., mannitol or phenol)
Rollover Participants

•Participants will be excluded from this study if any of the lead-in study exclusion criteria apply at the Screening Visit and at the end of the Run-in Period for randomization into the Treatment Period of studies RLM-MD-01 and RLM-MD-02, except as specified in the inclusion criteria
De Novo Participants
- History of anorexia nervosa, binge-eating, bulimia, or other eating disorder within 5 years of the Screening Visit
- History of intestinal malabsorption or pancreatic exocrine insufficiency
- History of belching disorders, other nausea and vomiting disorders
- Gastric or duodenal ulcer within 3 months of Screening
- History of malignancy in the 3 years prior to Screening, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
- Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube for feeding or decompression
- Use of metoclopramide, domperidone, prucalopride, macrolide antibiotics (e.g., erythromycin, clarithromycin, azithromycin), or other drugs considered to be GI promotility agents for at least 10 days prior to the start of the Run-in Period
- Currently taking opiates, or expecting to use opiates during the course of the clinical study
- Treatment with glucagon-like peptide-1 (GLP-1) agonist for at least 6 weeks prior to the start of the Run-in Period
- History of pyloric injection of botulinum toxin within 6 months of screening
- History of gastric surgery such as fundoplication, gastrectomy, gastric pacemaker placement, vagotomy, or bariatric procedure (a history of diagnostic endoscopy is not exclusionary)
- Randomization in any previous study in which relamorelin was a treatment
- Allergic to, or intolerant of egg, wheat, milk, or algae, as these are components of the gastric emptying breath test (GEBT) study meal

Name	Affiliation	Role
Harvy Schneier	Allergan	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pinnacle Research Group		Anniston	Alabama	36207	United States
North Alabama Research Center, LLC

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	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.
FG001	Relamorelin 10 μg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 12, 2021	Nov 19, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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 randomized participants with ≥1 postbaseline assessment of DGSSD. Number analyzed is the number of participants with data available for analysis at the given timepoint.

Posted

Mean

Standard Deviation

score on a scale

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

ID	Title	Description
OG000	Placebo	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.
OG001	Relamorelin 10 μg	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.

Units	Counts
Participants	OG000147 OG001295

Title

Denominators

Categories

Baseline

- ParticipantsOG000147
- ParticipantsOG001295

Title	Measurements
	OG00020.3± 6.70

Primary

Change From Baseline to Week 52 in the Weekly Average DGSSS

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 randomized participants with ≥1 postbaseline assessment of DGSSD. Number analyzed is the number of participants with data available for analysis at the given timepoint.

Posted

Mean

Standard Deviation

score on a scale

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

ID	Title	Description
OG000	Placebo	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.
OG001	Relamorelin 10 μg

Primary

Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAE)

An adverse event (AE) is any untoward medical occurrence in a patient 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.

Posted

Count of Participants

Participants

First dose of study drug to within 30 days of the last dose of study drug (Up to approximately 56 weeks)

ID	Title	Description
OG000	Placebo	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.
OG001	Relamorelin 10 μg	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.

Primary

Number of Participants With Potential Clinically Significant (PCS) Clinical Laboratory Results

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. Number analyzed is the number of participants with non-PCS Baseline values and at least one post-baseline assessment.

Posted

Count of Participants

Participants

Up to 52 weeks

ID	Title	Description
OG000	Placebo	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.
OG001	Relamorelin 10 μg	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.

Units	Counts

Primary

Number of Participants With Clinically Meaningful Trends for Vital Signs

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.

Posted

Count of Participants

Participants

Up to 52 weeks

ID	Title	Description
OG000	Placebo	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.
OG001	Relamorelin 10 μg	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.

Units	Counts
Participants

Primary

Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results

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.

Posted

Count of Participants

Participants

Up to 52 weeks

ID	Title	Description
OG000	Placebo	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.
OG001	Relamorelin 10 μg	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.

Units	Counts
Participants	OG000

Primary

Number of Participants With a ≥1% Increase in Glycosylated Hemoglobin A1c (HbA1c)

Safety Population included all participants who received ≥1 administration of study treatment.

Posted

Count of Participants

Participants

Up to 52 weeks

ID	Title	Description
OG000	Placebo	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.
OG001	Relamorelin 10 μg	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.

Units	Counts
Participants	OG000

Primary

Number of Participants With Anti-relamorelin Antibody Testing Results by Visit

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. Number analyzed is the number of participants with data available at the given timepoint. Due to a laboratory issue not all positive screening tests were confirmed.

Posted

Count of Participants

Participants

Baseline (Day 1), Day 84, Day 364, and End of Treatment (Up to Day 364)

ID	Title	Description
OG000	Relamorelin 10 μg	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.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac arrest	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Acute left ventricular failure	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected299 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Angina pectoris	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Angina unstable	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Atrial fibrillation	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Bradycardia	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Myocardial infarction	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Cardiac failure	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Sinus tachycardia	Cardiac disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Atrial septal defect	Congenital, familial and genetic disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Vertigo	Ear and labyrinth disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected299 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Constipation	Gastrointestinal disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Diabetic gastroparesis	Gastrointestinal disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Nausea	Gastrointestinal disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Non-cardiac chest pain	General disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Physical deconditioning	General disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Bronchitis	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Diverticulitis	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Sepsis	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Pneumonia	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0002 affected145 at risk EG0011 affected299 at risk
Bacteraemia	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
COVID-19	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Cellulitis	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Diabetic gangrene	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Herpes zoster	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Metapneumovirus infection	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Otitis media	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Urinary tract infection	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Urosepsis	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Appendicitis	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Diabetic foot infection	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Gastroenteritis	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Pneumonia pneumococcal	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Fall	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0013 affected299 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Blood glucose decreased	Investigations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Blood glucose increased	Investigations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Glomerular filtration rate decreased	Investigations	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0012 affected299 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0011 affected299 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Plasmacytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Cervical radiculopathy	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Headache	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Migraine	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Vertebral artery occlusion	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Presyncope	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Suicide attempt	Psychiatric disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Anxiety disorder	Psychiatric disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Major depression	Psychiatric disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0013 affected299 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk
Aortic stenosis	Vascular disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Hypertension	Vascular disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Hypotension	Vascular disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA: 23.1	Systematic Assessment	EG0000 affected145 at risk EG0011 affected299 at risk
Orthostatic hypotension	Vascular disorders	MedDRA: 23.1	Systematic Assessment	EG0001 affected145 at risk EG0010 affected299 at risk

ID	Term
D013272	Stomach Diseases
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D010243	Paralysis
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D012817	Signs and Symptoms, Digestive

ID	Title	Description
BG000	Placebo	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.
BG001	Relamorelin 10 μg	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	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.	0	148	21	145	37	145
EG001	Relamorelin 10 μg	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.	2	302	43	299	82	299

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA: 23.1	Systematic Assessment	EG00014 affected145 at risk EG00121 affected299 at risk
Urinary tract infection	Infections and infestations	MedDRA: 23.1	Systematic Assessment	EG0009 affected145 at risk EG00128 affected299 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA: 23.1	Systematic Assessment	EG0008 affected145 at risk EG00115 affected299 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA: 23.1	Systematic Assessment	EG00011 affected145 at risk EG00118 affected299 at risk
Headache	Nervous system disorders	MedDRA: 23.1	Systematic Assessment	EG0007 affected145 at risk EG00115 affected299 at risk