Safety and Efficacy of Relamorelin Administered to Participants With Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis
Diabetes Mellitus, Diabetes Mellitus Complications, Gastroparesis
About this trial
This is an interventional treatment trial for Diabetes Mellitus focused on measuring Diabetes Mellitus, Delayed Gastric Emptying, Vomiting, Gastroparesis, Gastrointestinal Motility Disorder
Eligibility Criteria
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.
Sites / Locations
- Digestive Health Specialist of the Southeast
- Desert Sun Clinical Research
- Adobe Clinical Research
- Harrisburg Family Medical Center
- Arkansas Primary Care Clinic
- Preferred Research Partners, Inc.
- TriWest Research Associates
- Torrance Clinical Research Institute Inc.
- Axis Clinical Trials
- Inland Empire Liver Foundation
- Syrentis Clinical Research
- Ventura Clinical Trials
- Danbury Hospital- Office of Clinical trials
- Avail Clinical Research
- International Research Associates LLC
- Nature Coast Clinical Research
- APF Research, LLC
- Advanced Pharma CR, LLC
- Baptist Diabetes Associates, P.A.
- International Research Associates LLC
- Advanced Research Institute Inc
- Advanced Medical Research Center
- Palm Beach Research Center
- River Birch Research Alliance LLC
- Rockford Gastroenterology Associates, Ltd.
- Medisphere Medical Research Center
- Professional Research Network of Kansas, LLC
- University of Louisville
- Delta Research Partners
- Clinical Trials of America LA, LLC
- Metropolitan Gastroenterology Group, P.C. (Chevy Chase Clinical Research) Chevy Chase Clinical Research
- Beth Israel Deaconess Medical Center
- Clinical Research Institute of Michigan, LLC
- Detroit Clinical Research Center, PC-Farmington Hills
- Center For Digestive Health
- Mayo Clinic
- Planters Clinic
- Impact Clinical Trials
- Advanced Biomedical Research of America
- New York Clinical Trials, Inc
- Cumberland Research Associates, LLC
- OnSite Clinical Solutions- Lexington OnSite Clinical Solutions, LLC
- Diabetes and Endocrinology Consultants, P.C.
- OnSite Clinical Solutions, LLC
- Trial Management Associates, LLC
- Wake Forest University Baptist Health - Dept of Gastroenterology Medical Center Blvd
- Consultants for Clinical Research
- Prestige Clinical Research
- MetroHealth Medical Center
- Great Lakes Gastroenterology Research
- Northwest Gastroenterology Clinic
- Family Medicine of SayeBrook
- ClinSearch LLC
- GI Specialists of Houston
- Houston Methodist Hospital
- The University of Texas Health Science Center & Medical School at Houston
- Texas Tech University Health Sciences Center
- Gulf Coast Medical Research, LLC
- Aspen Clinical Research
- Highland Clinical Research
- Gastroenterology Associates of Tidewater
- Khan and Abbasi Research
- Healing Hands of Virginia LLC
- Gastroenterology Consultants
- ZainResearch, LLC
- Hopital Erasme - Universite Libre de Bruxelles
- UZ Leuven
- Herz und Diabeteszentrum Nordrhein Westfalen, Universitätsklinikum der Ruhr-Universiät Bochum
- Praxis Dr. Ott Rabenauer Str.
- GWT-TUD GmbH
- Israelitisches Krankenhaus Orchideenstig
- Diabetes Zentrum und Praxis Prof. Pfützner Parcusstr.
- Rambam Health Care Campus - Inst. of Endocrinology, Diabetes, and Metabolism
- Wolfson Medical Center
- Rabin Medical Center, Beilinson Hospital Gastroenterology Dept
- ZIV Medical Center
- Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorób Kostno-Stawowych J. Badurski S.J. ul.
- NZOZ Witamed al.
- CenterMed Krakow
- Gabinet Lekarski dr n.med. Malgorzata Saryusz-Wolska ul.
- NZOZ Pulsmedica ul.
- KO-MED Centra Kliniczne
- Centrum Badawcze Wspólczesnej Terapii ul.
- Gastroenterology Karolinska University Hospital Karolinska Universitetssjukhuset Gastro Centrum Medicine
- Uppsala University Hospital Gastroenterology / Mag-Tarmmottagningen ingang
- NHS Tayside
- Wansbeck General Hospital (Northumbria NHS Trust)
- University Hospital of North Durham University Hospital of North Durham Research and Development Directorate
- Royal Liverpool University Hospital
- King's College Hospital
- The James Cook University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Placebo Comparator
Relamorelin 10 μg
Relamorelin 30 μg
Relamorelin 100 μg
Placebo
Relamorelin 10 microgram (μg) was administered subcutaneously (SC) by injection twice daily (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.
Placebo-matching relamorelin was administered SC by injection BID for 12 weeks.