Safety and Efficacy of Relamorelin Administered to Participants With Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02357420
• Collaborator: (none)
• Enrollment: 393
• Locations: 98
• Arms: 4
• Actual Duration (Months): 16.3
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of multiple dose regimens of relamorelin on vomiting episodes, gastric emptying and gastroparesis symptoms in participants with Type 1 and Type 2 diabetes mellitus and gastroparesis. Study drug (relamorelin and placebo) will be administered subcutaneously in a blinded fashion.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus; Diabetes Mellitus Complications; Gastroparesis	Drug: Relamorelin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 393 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of RM-131 Administered to Patients With Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis
• Actual Study Start Date: Jan 29, 2015
• Actual Primary Completion Date: Jun 9, 2016
• Actual Study Completion Date: Jun 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relamorelin 10 μg Relamorelin 10 microgram (μg) was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Drug: Relamorelin; Double blind relamorelin was given subcutaneously BID for 12 weeks.; Other Names: RM-131
Experimental: Relamorelin 30 μg Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Drug: Relamorelin; Double blind relamorelin was given subcutaneously BID for 12 weeks.; Other Names: RM-131
Experimental: Relamorelin 100 μg Relamorelin 100 μg was administered SC by injection BID for 12 weeks.	Drug: Relamorelin; Double blind relamorelin was given subcutaneously BID for 12 weeks.; Other Names: RM-131
Placebo Comparator: Placebo Placebo-matching relamorelin was administered SC by injection BID for 12 weeks.	Drug: Placebo; Placebo given subcutaneously for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 12 in Weekly Vomiting Episodes [7 days prior to Day 1 for Baseline to 7 days prior to Week 12]

   Vomiting episodes were assessed via the Diabetic Gastroparesis Symptoms Severity Diary (DGSSD). The DGSSD is a 7-item, participant-reported daily diary designed to assess the severity of 6 core signs and symptoms of Diabetic Gastroparesis (DG) (nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety) and the frequency of vomiting episodes. Each day, the participant recorded the number of vomiting episodes in the past 24 hours in the diary. Higher scores indicate more vomiting episodes. Weekly scores were averaged across the 12 weeks period. A negative change from Baseline indicates improvement.

Secondary Outcome Measures

1. Change From Baseline to Week 12 in Weekly DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal Pain) [7 days prior to Day 1 for Baseline to 7 days prior to Week 12]

   The DGSSD is a 7-item, participant-reported daily diary designed to assess the severity of 6 core signs and symptoms of DG (nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety) and the frequency of vomiting episodes. Severity of nausea, bloating and abdominal pain, were assessed on a numerical rating scale of 0 to 10, with 0 equating to "no" (symptom) and 10 equating to "worst possible" (symptom). Early satiety was assessed on a 5-item scale with 1 being "Only 1 or 2 bites" and 5 being "All of a normal-sized meal"; symptom severity scores for this item were reversed and normalized to a range 0 to 10 for the development of the DGSSD 4-symptom Composite Score. The DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal pain) range is 0 to 40. Higher scores indicate worse condition. Weekly scores were averaged across 12 weeks period. A negative change from Baseline indicates improvement.

2. Change From Baseline to Week 12 for Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-time [Baseline (Day 1) to Week 12]

   GE was measured via the GEBT and was reported as a time to half (t1/2) of the theoretical total GE. GEBT is a non-radioactive stable isotope breath test intended for measurement of GE of solids in participants. A negative change from Baseline indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM) with stable glycemic control and Hemoglobin A1c (HbA1c) ≤11% at screening.

• Diabetic gastroparesis (DG), defined as at least a 3-month history of symptoms suggestive of gastroparesis on an ongoing basis (e.g., vomiting, nausea, early satiety, bloating, or epigastric or abdominal pain).

• Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) score ≥2.6 at least once during the Screening Period (Visits 1-2).

• At least 2 vomiting episodes during the ~2 weeks prior to the first screening visit (Visit 1), as ascertained by patient history.

• Delayed Gastric Emptying (GE) confirmed at screening by abnormal Gastric Emptying Breath Test (GEBT), defined as GE half-time (t1/2) ≥79 minutes (the 80th percentile of normative data). At least 50% of patients enrolled will have a t1/2 ≥97 minutes (i.e., the 95th percentile).

• Stable concomitant medications, defined as no changes in regimen for at least 2 weeks prior to Visit 2 (daily adjustments of insulin doses are permitted).

• No use of metoclopramide, erythromycin, domperidone, or other gastrointestinal (GI) motility agents, or anti-emetics for at least 2 weeks prior to Visit 2, and willingness to remain off these medications (except as used as part of protocol-specific rescue medication) during the course of the clinical trial.

• Body mass index >18 kg/m2.

• If female, has a negative serum or urine pregnancy test and is not lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. Female patients unable to bear children must have this documented in the electronic case report form (eCRF) (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of 1 year since the last menstrual period]). Post-menopausal status will be confirmed by measurement of follicle stimulating hormone (FSH).

• Able to provide written informed consent prior to any study procedures and willing and able to comply with study procedures.

Additional inclusion criteria for randomization after the 2-week single-blind placebo run-in period:

• Compliance with the completion of the Diabetic Gastroparesis Symptom Severity Diary (DGSSD) and study drug injections, defined as approximately 80% diary completions and approximately 80% administration of injections, during the 2-week single-blind placebo run-in period. For those patients whose compliance is measured to be <80%, the final decision to randomize a patient will be made by the Investigator and the Sponsor (or designee).

• At least one vomiting episode at any time during the 2-week single-blind placebo run-in period, as recorded in the DGSSD.

Exclusion Criteria:

• Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube [e.g., Percutaneous Endoscopic Gastrostomy (PEG) tube] for feeding or decompression.

• History of gastric surgery such as fundoplication, gastrectomy, gastric pacemaker placement, vagotomy, or bariatric procedure. (A history of diagnostic endoscopy is not exclusionary.)

• History of pyloric injection of botulinum toxin within 6 months of screening.

• Patients with clinical suspicion of upper GI obstruction (e.g., peptic stricture) must have been evaluated per standard of care and obstruction ruled out before screening.

• Currently taking opiates, or expecting to use opiates during the course of the clinical trial.

• Currently taking Glucagon-like peptide-1 (GLP-1) agonists, Sodium-glucose co-transporter 2 (SGLT2) inhibitors or pramlintide.

• Allergic or intolerant of egg, wheat, milk, or algae, as these are components of the Gastric emptying breath test (GEBT) study meal. (Gluten-free crackers can be provided.)

• History of anorexia nervosa, binge-eating, or bulimia within 5 years of screening.

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN) at Visit 1.

• History of intestinal malabsorption or pancreatic exocrine disease.

• Requires hemodialysis or has end-stage renal disease.

• History of human immunodeficiency virus (HIV) infection.

• Clinically significant neurologic or psychiatric disorders that are likely to impact compliance with protocol requirements.

• Poor venous access or inability to tolerate venipuncture.

• Participation in a clinical study within the 30 days prior to dosing in the present study.

• Any other reason that, in the Investigator's opinion, would confound proper interpretation of the study or expose a patient to unacceptable risk, including renal, hepatic or cardiopulmonary disease, or significant acute electrocardiogram (ECG) abnormalities.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Digestive Health Specialist of the Southeast	Dothan	Alabama	United States	36305
2		Huntsville	Alabama	United States	35801
3	Desert Sun Clinical Research	Tucson	Arizona	United States	85710
4	Adobe Clinical Research	Tucson	Arizona	United States	85712
5	Harrisburg Family Medical Center	Harrisburg	Arkansas	United States	72432
6	Arkansas Primary Care Clinic	Little Rock	Arkansas	United States	72204
7	Preferred Research Partners, Inc.	Little Rock	Arkansas	United States	72211
8	TriWest Research Associates	El Cajon	California	United States	92020
9	Torrance Clinical Research Institute Inc.	Lomita	California	United States	90717
10	Axis Clinical Trials	Los Angeles	California	United States	90036
11	Inland Empire Liver Foundation	Rialto	California	United States	92377
12	Syrentis Clinical Research	Santa Ana	California	United States	92705
13	Ventura Clinical Trials	Ventura	California	United States	93003
14	Danbury Hospital- Office of Clinical trials	Danbury	Connecticut	United States	06810
15	Avail Clinical Research	DeLand	Florida	United States	32720
16	International Research Associates LLC	Hialeah	Florida	United States	33012
17	Nature Coast Clinical Research	Inverness	Florida	United States	34452
18	APF Research, LLC	Miami	Florida	United States	33135
19	Advanced Pharma CR, LLC	Miami	Florida	United States	33136
20	Baptist Diabetes Associates, P.A.	Miami	Florida	United States	33156
21		Miami	Florida	United States	33175
22	International Research Associates LLC	Miami	Florida	United States	33183
23	Advanced Research Institute Inc	New Port Richey	Florida	United States	34655
24	Advanced Medical Research Center	Port Orange	Florida	United States	32127
25	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
26	River Birch Research Alliance LLC	Blue Ridge	Georgia	United States	30513
27	Rockford Gastroenterology Associates, Ltd.	Rockford	Illinois	United States	61107
28	Medisphere Medical Research Center	Evansville	Indiana	United States	47714
29	Professional Research Network of Kansas, LLC	Wichita	Kansas	United States	67203
30	University of Louisville	Louisville	Kentucky	United States	40202
31	Delta Research Partners	Monroe	Louisiana	United States	71201
32	Clinical Trials of America LA, LLC	West Monroe	Louisiana	United States	71291
33	Metropolitan Gastroenterology Group, P.C. (Chevy Chase Clinical Research) Chevy Chase Clinical Research	Chevy Chase	Maryland	United States	20815
34	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
35		Ann Arbor	Michigan	United States	48109
36	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan	United States	48047
37	Detroit Clinical Research Center, PC-Farmington Hills	Farmington Hills	Michigan	United States	48334
38	Center For Digestive Health	Troy	Michigan	United States	48098
39	Mayo Clinic	Rochester	Minnesota	United States	55905
40	Planters Clinic	Port Gibson	Mississippi	United States	39150
41	Impact Clinical Trials	Las Vegas	Nevada	United States	89106
42	Advanced Biomedical Research of America	Las Vegas	Nevada	United States	89123
43		Great Neck	New York	United States	11023
44	New York Clinical Trials, Inc	New York	New York	United States	10018
45	Cumberland Research Associates, LLC	Fayetteville	North Carolina	United States	28304
46	OnSite Clinical Solutions- Lexington OnSite Clinical Solutions, LLC	Lexington	North Carolina	United States	27292
47	Diabetes and Endocrinology Consultants, P.C.	Morehead City	North Carolina	United States	28557
48	OnSite Clinical Solutions, LLC	Statesville	North Carolina	United States	28117
49	Trial Management Associates, LLC	Wilmington	North Carolina	United States	28403
50	Wake Forest University Baptist Health - Dept of Gastroenterology Medical Center Blvd	Winston-Salem	North Carolina	United States	27107
51	Consultants for Clinical Research	Cincinnati	Ohio	United States	45219
52	Prestige Clinical Research	Franklin	Ohio	United States	45005
53	MetroHealth Medical Center	Leveland	Ohio	United States	44109
54	Great Lakes Gastroenterology Research	Mentor	Ohio	United States	44060
55	Northwest Gastroenterology Clinic	Portland	Oregon	United States	97210
56	Family Medicine of SayeBrook	Myrtle Beach	South Carolina	United States	29588
57	ClinSearch LLC	Chattanooga	Tennessee	United States	37421
58		El Paso	Texas	United States	79905
59	GI Specialists of Houston	Houston	Texas	United States	77015
60	Houston Methodist Hospital	Houston	Texas	United States	77030
61	The University of Texas Health Science Center & Medical School at Houston	Houston	Texas	United States	77030
62	Texas Tech University Health Sciences Center	Lubbock	Texas	United States	79430
63	Gulf Coast Medical Research, LLC	Sugar Land	Texas	United States	77478
64	Aspen Clinical Research	Orem	Utah	United States	84058
65	Highland Clinical Research	Salt Lake City	Utah	United States	84095
66	Gastroenterology Associates of Tidewater	Chesapeake	Virginia	United States	23320
67	Khan and Abbasi Research	Chester	Virginia	United States	23831
68	Healing Hands of Virginia LLC	Richmond	Virginia	United States	23225
69	Gastroenterology Consultants	Virginia Beach	Virginia	United States	23455
70	ZainResearch, LLC	Richland	Washington	United States	99352
71	Hopital Erasme - Universite Libre de Bruxelles	Brussels		Belgium	1070
72	UZ Leuven	Leuven		Belgium	3000
73	Herz und Diabeteszentrum Nordrhein Westfalen, Universitätsklinikum der Ruhr-Universiät Bochum	Bad Oeynhausen		Germany	32545
74	Praxis Dr. Ott Rabenauer Str.	Dippoldiswalde		Germany	01744
75	GWT-TUD GmbH	Dresden		Germany	01307
76	Israelitisches Krankenhaus Orchideenstig	Hamburg		Germany	22297
77	Diabetes Zentrum und Praxis Prof. Pfützner Parcusstr.	Mainz		Germany	55116
78	Rambam Health Care Campus - Inst. of Endocrinology, Diabetes, and Metabolism	Haifa		Israel	31096
79	Wolfson Medical Center	Holon		Israel	58100
80	Rabin Medical Center, Beilinson Hospital Gastroenterology Dept	Petach Tikva		Israel	49100
81	ZIV Medical Center	Safed		Israel	13100
82	Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorób Kostno-Stawowych J. Badurski S.J. ul.	Bialystok		Poland	15-879
83	NZOZ Witamed al.	Kielce		Poland	25-035
84	CenterMed Krakow	Krakow		Poland	31530
85	Gabinet Lekarski dr n.med. Malgorzata Saryusz-Wolska ul.	Lodz		Poland	90-132
86	NZOZ Pulsmedica ul.	Lodz		Poland	93-509
87	KO-MED Centra Kliniczne	Staszów		Poland	28-200
88	Centrum Badawcze Wspólczesnej Terapii ul.	Warszawa		Poland	02-679
89		Warszawa		Poland	02-679
90	Gastroenterology Karolinska University Hospital Karolinska Universitetssjukhuset Gastro Centrum Medicine	Stockholm		Sweden	141 86
91	Uppsala University Hospital Gastroenterology / Mag-Tarmmottagningen ingang	Uppsala		Sweden	SE-751 85
92	NHS Tayside	Dundee	Scotland	United Kingdom	DD1 9SY
93	Wansbeck General Hospital (Northumbria NHS Trust)	Ashington		United Kingdom	NE63 9JJ
94	University Hospital of North Durham University Hospital of North Durham Research and Development Directorate	Durham		United Kingdom	DH1 5TW
95	Royal Liverpool University Hospital	Liverpool		United Kingdom	L7 8XP
96	King's College Hospital	London		United Kingdom	SE5 9RS
97	The James Cook University Hospital	Middlesbrough		United Kingdom	TS4 3BW
98		Tyne And Wear		United Kingdom	NE29 8NH

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Wieslaw Bochenek, MD, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02357420
• Other Study ID Numbers: RM-131-009; 2014-005623-27
• First Posted: Feb 6, 2015
• Last Update Posted: Jul 24, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Allergan: Diabetes Mellitus; Delayed Gastric Emptying; Vomiting; Gastroparesis; Gastrointestinal Motility Disorder
• Additional relevant MeSH terms: Gastroparesis; Diabetes Mellitus; Diabetes Complications; Vomiting

Study Results

Participant Flow

Pre-assignment Detail	A total 393 participants were randomized and received study treatment, and 334 participants completed the study. Five participants who received study drug but discontinued prematurely were summarized as completing the study because they fulfilled the Visit 8 (Week 12) assessments as per protocol.

Arm/Group Title	Placebo	Relamorelin 10 μg	Relamorelin 30 μg	Relamorelin 100 μg
Arm/Group Description	Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Period Title: Overall Study
STARTED	104	98	109	82
Full Analysis Set (FAS)	104	98	109	81
COMPLETED	92	86	93	63
NOT COMPLETED	12	12	16	19

Baseline Characteristics

Arm/Group Title	Placebo	Relamorelin 10 μg	Relamorelin 30 μg	Relamorelin 100 μg	Total
Arm/Group Description	Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg was administered SC by injection BID for 12 weeks.	Total of all reporting groups
Overall Participants	104	98	109	82	393
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.7 (11.9)	59.3 (10.2)	56.0 (11.7)	57.1 (11.0)	57.0 (11.3)
Sex: Female, Male (Count of Participants)
Female	64 61.5%	59 60.2%	65 59.6%	57 69.5%	245 62.3%
Male	40 38.5%	39 39.8%	44 40.4%	25 30.5%	148 37.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 12 in Weekly Vomiting Episodes
Description	Vomiting episodes were assessed via the Diabetic Gastroparesis Symptoms Severity Diary (DGSSD). The DGSSD is a 7-item, participant-reported daily diary designed to assess the severity of 6 core signs and symptoms of Diabetic Gastroparesis (DG) (nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety) and the frequency of vomiting episodes. Each day, the participant recorded the number of vomiting episodes in the past 24 hours in the diary. Higher scores indicate more vomiting episodes. Weekly scores were averaged across the 12 weeks period. A negative change from Baseline indicates improvement.
Time Frame	7 days prior to Day 1 for Baseline to 7 days prior to Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study treatment and provided at least 1 postbaseline primary efficacy measurement (DGSSD). Number analyzed is the number of participants with data available at the given time-point.

Arm/Group Title	Placebo	Relamorelin 10 μg	Relamorelin 30 μg	Relamorelin 100 μg
Arm/Group Description	Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Measure Participants	104	98	109	81
Baseline	5.7 (6.0)	7.7 (17.2)	6.9 (10.3)	4.8 (5.2)
Change from Baseline to Week 12	-2.9 (5.8)	-3.7 (12.5)	-3.8 (7.6)	-1.1 (13.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Relamorelin 10 μg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Measures mixed effects model (MMRM)
	Comments	MMRM analysis used treatment, week, treatment-by-week interaction as fixed factors and baseline values as the covariates.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Relamorelin 30 μg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	MMRM
	Comments	MMRM analysis used treatment, week, treatment-by-week interaction as fixed factors and baseline values as the covariates.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Relamorelin 100 μg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	MMRM
	Comments	MMRM analysis used treatment, week, treatment-by-week interaction as fixed factors and baseline values as the covariates.

2. Secondary Outcome

Title	Change From Baseline to Week 12 in Weekly DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal Pain)
Description	The DGSSD is a 7-item, participant-reported daily diary designed to assess the severity of 6 core signs and symptoms of DG (nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety) and the frequency of vomiting episodes. Severity of nausea, bloating and abdominal pain, were assessed on a numerical rating scale of 0 to 10, with 0 equating to "no" (symptom) and 10 equating to "worst possible" (symptom). Early satiety was assessed on a 5-item scale with 1 being "Only 1 or 2 bites" and 5 being "All of a normal-sized meal"; symptom severity scores for this item were reversed and normalized to a range 0 to 10 for the development of the DGSSD 4-symptom Composite Score. The DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal pain) range is 0 to 40. Higher scores indicate worse condition. Weekly scores were averaged across 12 weeks period. A negative change from Baseline indicates improvement.
Time Frame	7 days prior to Day 1 for Baseline to 7 days prior to Week 12

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of study treatment and provided at least 1 postbaseline primary efficacy measurement (DGSSD). Number analyzed is the number of participants with data available at the given time-point.

Arm/Group Title	Placebo	Relamorelin 10 μg	Relamorelin 30 μg	Relamorelin 100 μg
Arm/Group Description	Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Measure Participants	104	98	109	81
Baseline	21.4 (6.7)	21.8 (6.9)	21.1 (6.0)	22.3 (6.2)
Change from Baseline to Week 12	-5.4 (8.1)	-7.7 (7.8)	-7.5 (7.4)	-8.9 (8.3)

3. Secondary Outcome

Title	Change From Baseline to Week 12 for Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-time
Description	GE was measured via the GEBT and was reported as a time to half (t1/2) of the theoretical total GE. GEBT is a non-radioactive stable isotope breath test intended for measurement of GE of solids in participants. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Week 12

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least 1 dose of study treatment and provided at least 1 postbaseline primary efficacy measurement (DGSSD). Number analyzed is the number of participants with data available at the given time-point.

Arm/Group Title	Placebo	Relamorelin 10 μg	Relamorelin 30 μg	Relamorelin 100 μg
Arm/Group Description	Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Measure Participants	104	98	109	81
Baseline	127.1 (36.5)	126.8 (37.6)	128.6 (35.9)	133.6 (35.4)
Change from Baseline to Week 12	0.0 (38.5)	-12.7 (38.1)	-12.8 (36.5)	-13.6 (40.5)

Adverse Events

Time Frame	Up to 98 days
Adverse Event Reporting Description	Safety set included all the participants who were randomized and received at least 1 dose of study treatment.
Arm/Group Title	Placebo		Relamorelin 10 μg		Relamorelin 30 μg		Relamorelin 100 μg
Arm/Group Description	Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.		Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.		Relamorelin 30 μg was administered SC by injection BID for 12 weeks.		Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
All Cause Mortality
	Placebo		Relamorelin 10 μg		Relamorelin 30 μg		Relamorelin 100 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		0/98 (0%)		0/109 (0%)		1/82 (1.2%)
Serious Adverse Events
	Placebo		Relamorelin 10 μg		Relamorelin 30 μg		Relamorelin 100 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/104 (7.7%)		7/98 (7.1%)		10/109 (9.2%)		6/82 (7.3%)
Cardiac disorders
Angina unstable	0/104 (0%)		0/98 (0%)		2/109 (1.8%)		0/82 (0%)
Angina pectoris	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Arteriosclerosis coronary artery	0/104 (0%)		1/98 (1%)		0/109 (0%)		0/82 (0%)
Cardiac failure congestive	0/104 (0%)		0/98 (0%)		0/109 (0%)		1/82 (1.2%)
Cardio-respiratory arrest	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Gastrointestinal disorders
Impaired gastric emptying	2/104 (1.9%)		1/98 (1%)		0/109 (0%)		1/82 (1.2%)
Gastritis	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Gastroduodenitis	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Pancreatitis acute	0/104 (0%)		1/98 (1%)		0/109 (0%)		0/82 (0%)
Small intestinal obstruction	0/104 (0%)		1/98 (1%)		0/109 (0%)		0/82 (0%)
General disorders
Non-cardiac chest pain	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Hepatobiliary disorders
Biliary tract disorder	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Cholecystitis acute	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Infections and infestations
Escherichia urinary tract infection	0/104 (0%)		0/98 (0%)		0/109 (0%)		1/82 (1.2%)
Pneumonia	0/104 (0%)		1/98 (1%)		0/109 (0%)		0/82 (0%)
Pyelonephritis	0/104 (0%)		1/98 (1%)		0/109 (0%)		0/82 (0%)
Urinary tract infection	0/104 (0%)		0/98 (0%)		0/109 (0%)		1/82 (1.2%)
Urosepsis	0/104 (0%)		0/98 (0%)		0/109 (0%)		1/82 (1.2%)
Injury, poisoning and procedural complications
Laceration	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Median nerve injury	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Traumatic hematoma	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/104 (0%)		1/98 (1%)		1/109 (0.9%)		0/82 (0%)
Diabetes mellitus inadequate control	0/104 (0%)		0/98 (0%)		0/109 (0%)		1/82 (1.2%)
Hyperglycaemia	0/104 (0%)		0/98 (0%)		0/109 (0%)		1/82 (1.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Nervous system disorders
Hemiparesis	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Syncope	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Psychiatric disorders
Depression	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Renal and urinary disorders
Renal failure acute	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		1/82 (1.2%)
Nephrolithiasis	0/104 (0%)		1/98 (1%)		0/109 (0%)		0/82 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/104 (1%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Dyspnea	0/104 (0%)		0/98 (0%)		1/109 (0.9%)		0/82 (0%)
Vascular disorders
Orthostatic hypotension	1/104 (1%)		0/98 (0%)		0/109 (0%)		0/82 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Relamorelin 10 μg		Relamorelin 30 μg		Relamorelin 100 μg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/104 (12.5%)		21/98 (21.4%)		30/109 (27.5%)		28/82 (34.1%)
Gastrointestinal disorders
Diarrhoea	0/104 (0%)		4/98 (4.1%)		7/109 (6.4%)		6/82 (7.3%)
Infections and infestations
Urinary tract infection	7/104 (6.7%)		7/98 (7.1%)		8/109 (7.3%)		6/82 (7.3%)
Investigations
Blood glucose increased	1/104 (1%)		3/98 (3.1%)		4/109 (3.7%)		6/82 (7.3%)
Metabolism and nutrition disorders
Hyperglycaemia	2/104 (1.9%)		5/98 (5.1%)		10/109 (9.2%)		10/82 (12.2%)
Nervous system disorders
Dizziness	1/104 (1%)		0/98 (0%)		1/109 (0.9%)		5/82 (6.1%)
Headache	3/104 (2.9%)		4/98 (4.1%)		6/109 (5.5%)		2/82 (2.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.