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

Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02357420
• Other study ID #: RM-131-009
• Secondary ID: 2014-005623-27
• Status: Completed
• Phase: Phase 2
• Start date: January 29, 2015
• Est. completion date: June 9, 2016

Study information

• Verified date: June 2019
• Source: Allergan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 393
• Est. completion date: June 9, 2016
• Est. primary completion date: June 9, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Complications
• Diabetes Mellitus
• Diabetes Mellitus Complications
• Gastroparesis
• Vomiting

Intervention

Drug:
• Relamorelin
Double blind relamorelin was given subcutaneously BID for 12 weeks.
• Placebo
Placebo given subcutaneously for 12 weeks.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Allergan

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Israel,  Poland,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 12 in Weekly Vomiting Episodes	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.	7 days prior to Day 1 for Baseline to 7 days prior to Week 12
Secondary	Change From Baseline to Week 12 in Weekly DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal Pain)	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.	7 days prior to Day 1 for Baseline to 7 days prior to Week 12
Secondary	Change From Baseline to Week 12 for Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-time	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.	Baseline (Day 1) to Week 12