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

Phase 2

Completed

Conditions: Diabetes Mellitus
Diabetes Mellitus Complications
Gastroparesis

Interventions: Drug: Relamorelin
Drug: Placebo

Registration Number: NCT02357420

Lead Sponsor: Allergan

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 393

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Relamorelin 10 μg	Relamorelin	Relamorelin 10 microgram (μg) was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.
Relamorelin 30 μg	Relamorelin	Relamorelin 30 μg was administered SC by injection BID for 12 weeks.
Relamorelin 100 μg	Relamorelin	Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Placebo	Placebo	Placebo-matching relamorelin was administered SC by injection BID for 12 weeks.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.

Trial Locations

Locations (90): Syrentis Clinical Research
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Santa Ana, California, United States
River Birch Research Alliance LLC
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Blue Ridge, Georgia, United States
Gastroenterology Consultants
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Virginia Beach, Virginia, United States
Houston Methodist Hospital
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Houston, Texas, United States
The University of Texas Health Science Center & Medical School at Houston
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Houston, Texas, United States
Impact Clinical Trials
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Las Vegas, Nevada, United States
APF Research, LLC
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Miami, Florida, United States
Advanced Biomedical Research of America
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Las Vegas, Nevada, United States
Consultants for Clinical Research
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Cincinnati, Ohio, United States
NHS Tayside
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Dundee, Scotland, United Kingdom
Mayo Clinic
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Rochester, Minnesota, United States
Highland Clinical Research
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Salt Lake City, Utah, United States
Arkansas Primary Care Clinic
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Little Rock, Arkansas, United States
Harrisburg Family Medical Center
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Harrisburg, Arkansas, United States
New York Clinical Trials, Inc
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New York, New York, United States
Wolfson Medical Center
🇮🇱
Holon, Israel
Northwest Gastroenterology Clinic
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Portland, Oregon, United States
Digestive Health Specialist of the Southeast
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Dothan, Alabama, United States
Desert Sun Clinical Research
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Tucson, Arizona, United States
Adobe Clinical Research
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Tucson, Arizona, United States
Preferred Research Partners, Inc.
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Little Rock, Arkansas, United States
Inland Empire Liver Foundation
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Rialto, California, United States
TriWest Research Associates
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El Cajon, California, United States
Avail Clinical Research
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DeLand, Florida, United States
Torrance Clinical Research Institute Inc.
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Lomita, California, United States
International Research Associates LLC
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Miami, Florida, United States
Ventura Clinical Trials
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Ventura, California, United States
Nature Coast Clinical Research
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Inverness, Florida, United States
Advanced Pharma CR, LLC
🇺🇸
Miami, Florida, United States
Baptist Diabetes Associates, P.A.
🇺🇸
Miami, Florida, United States
Advanced Medical Research Center
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Port Orange, Florida, United States
Palm Beach Research Center
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West Palm Beach, Florida, United States
Professional Research Network of Kansas, LLC
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Wichita, Kansas, United States
Medisphere Medical Research Center
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Evansville, Indiana, United States
Delta Research Partners
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Monroe, Louisiana, United States
Metropolitan Gastroenterology Group, P.C. (Chevy Chase Clinical Research) Chevy Chase Clinical Research
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Chevy Chase, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Detroit Clinical Research Center, PC-Farmington Hills
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Farmington Hills, Michigan, United States
Center For Digestive Health
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Troy, Michigan, United States
Clinical Research Institute of Michigan, LLC
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Chesterfield, Michigan, United States
Planters Clinic
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Port Gibson, Mississippi, United States
Cumberland Research Associates, LLC
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Fayetteville, North Carolina, United States
Diabetes and Endocrinology Consultants, P.C.
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Morehead City, North Carolina, United States
OnSite Clinical Solutions, LLC
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Statesville, North Carolina, United States
Trial Management Associates, LLC
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Wilmington, North Carolina, United States
Wake Forest University Baptist Health - Dept of Gastroenterology Medical Center Blvd
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Winston-Salem, North Carolina, United States
Prestige Clinical Research
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Franklin, Ohio, United States
MetroHealth Medical Center
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Leveland, Ohio, United States
Great Lakes Gastroenterology Research
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Mentor, Ohio, United States
Family Medicine of SayeBrook
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Myrtle Beach, South Carolina, United States
ClinSearch LLC
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Chattanooga, Tennessee, United States
GI Specialists of Houston
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Houston, Texas, United States
Texas Tech University Health Sciences Center
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Lubbock, Texas, United States
Gulf Coast Medical Research, LLC
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Sugar Land, Texas, United States
Aspen Clinical Research
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Orem, Utah, United States
Gastroenterology Associates of Tidewater
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Chesapeake, Virginia, United States
Khan and Abbasi Research
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Chester, Virginia, United States
Healing Hands of Virginia LLC
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Richmond, Virginia, United States
ZainResearch, LLC
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Richland, Washington, United States
Herz und Diabeteszentrum Nordrhein Westfalen, Universitätsklinikum der Ruhr-Universiät Bochum
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Bad Oeynhausen, Germany
Hopital Erasme - Universite Libre de Bruxelles
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Brussels, Belgium
UZ Leuven
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Leuven, Belgium
GWT-TUD GmbH
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Dresden, Germany
Praxis Dr. Ott Rabenauer Str.
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Dippoldiswalde, Germany
Rambam Health Care Campus - Inst. of Endocrinology, Diabetes, and Metabolism
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Haifa, Israel
Israelitisches Krankenhaus Orchideenstig
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Hamburg, Germany
Rabin Medical Center, Beilinson Hospital Gastroenterology Dept
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Petach Tikva, Israel
Diabetes Zentrum und Praxis Prof. Pfützner Parcusstr.
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Mainz, Germany
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorób Kostno-Stawowych J. Badurski S.J. ul.
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Bialystok, Poland
CenterMed Krakow
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Krakow, Poland
NZOZ Witamed al.
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Kielce, Poland
Gabinet Lekarski dr n.med. Malgorzata Saryusz-Wolska ul.
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Lodz, Poland
KO-MED Centra Kliniczne
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Staszów, Poland
NZOZ Pulsmedica ul.
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Lodz, Poland
Centrum Badawcze Wspólczesnej Terapii ul.
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Warszawa, Poland
Wansbeck General Hospital (Northumbria NHS Trust)
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Ashington, United Kingdom
Gastroenterology Karolinska University Hospital Karolinska Universitetssjukhuset Gastro Centrum Medicine
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Stockholm, Sweden
Uppsala University Hospital Gastroenterology / Mag-Tarmmottagningen ingang
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Uppsala, Sweden
University Hospital of North Durham University Hospital of North Durham Research and Development Directorate
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Durham, United Kingdom
The James Cook University Hospital
🇬🇧
Middlesbrough, United Kingdom
King's College Hospital
🇬🇧
London, United Kingdom
Rockford Gastroenterology Associates, Ltd.
🇺🇸
Rockford, Illinois, United States
OnSite Clinical Solutions- Lexington OnSite Clinical Solutions, LLC
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Lexington, North Carolina, United States
Axis Clinical Trials
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Los Angeles, California, United States
Danbury Hospital- Office of Clinical trials
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Danbury, Connecticut, United States
Clinical Trials of America LA, LLC
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West Monroe, Louisiana, United States
Advanced Research Institute Inc
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New Port Richey, Florida, United States
ZIV Medical Center
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Safed, Israel
University of Louisville
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Louisville, Kentucky, United States
Royal Liverpool University Hospital
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Liverpool, United Kingdom