Clinical trial NCT02357420: Safety and Efficacy of Relamorelin Administered to Participants With Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus
Diabetes Mellitus Complications
Gastroparesis
Keywords: Diabetes Mellitus
Delayed Gastric Emptying
Vomiting
Gastroparesis
Gastrointestinal Motility Disorder
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2015-02-06
Enrollment: 393
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline to Week 12 in Weekly Vomiting Episodes
timeFrame: 7 days prior to Day 1 for Baseline to 7 days prior to Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 in Weekly DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal Pain)
timeFrame: 7 days prior to Day 1 for Baseline to 7 days prior to Week 12
measure: Change From Baseline to Week 12 for Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-time
timeFrame: Baseline (Day 1) to Week 12
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialist of the Southeast
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Tucson
country: United States
facility: Desert Sun Clinical Research
state: Arizona
city: Tucson
country: United States
facility: Adobe Clinical Research
state: Arizona
city: Harrisburg
country: United States
facility: Harrisburg Family Medical Center
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic
state: Arkansas
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc.
state: Arkansas
city: El Cajon
country: United States
facility: TriWest Research Associates
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute Inc.
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Danbury
country: United States
facility: Danbury Hospital- Office of Clinical trials
state: Connecticut
city: DeLand
country: United States
facility: Avail Clinical Research
state: Florida
city: Hialeah
country: United States
facility: International Research Associates LLC
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Miami
country: United States
facility: APF Research, LLC
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates, P.A.
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
facility: International Research Associates LLC
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute Inc
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Blue Ridge
country: United States
facility: River Birch Research Alliance LLC
state: Georgia
city: Rockford
country: United States
facility: Rockford Gastroenterology Associates, Ltd.
state: Illinois
city: Evansville
country: United States
facility: Medisphere Medical Research Center
state: Indiana
city: Wichita
country: United States
facility: Professional Research Network of Kansas, LLC
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Monroe
country: United States
facility: Delta Research Partners
state: Louisiana
city: West Monroe
country: United States
facility: Clinical Trials of America LA, LLC
state: Louisiana
city: Chevy Chase
country: United States
facility: Metropolitan Gastroenterology Group, P.C. (Chevy Chase Clinical Research) Chevy Chase Clinical Research
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center, PC-Farmington Hills
state: Michigan
city: Troy
country: United States
facility: Center For Digestive Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Port Gibson
country: United States
facility: Planters Clinic
state: Mississippi
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Great Neck
country: United States
state: New York
city: New York
country: United States
facility: New York Clinical Trials, Inc
state: New York
city: Fayetteville
country: United States
facility: Cumberland Research Associates, LLC
state: North Carolina
city: Lexington
country: United States
facility: OnSite Clinical Solutions- Lexington OnSite Clinical Solutions, LLC
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes and Endocrinology Consultants, P.C.
state: North Carolina
city: Statesville
country: United States
facility: OnSite Clinical Solutions, LLC
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Health - Dept of Gastroenterology Medical Center Blvd
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Leveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology Research
state: Ohio
city: Portland
country: United States
facility: Northwest Gastroenterology Clinic
state: Oregon
city: Myrtle Beach
country: United States
facility: Family Medicine of SayeBrook
state: South Carolina
city: Chattanooga
country: United States
facility: ClinSearch LLC
state: Tennessee
city: El Paso
country: United States
state: Texas
city: Houston
country: United States
facility: GI Specialists of Houston
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center & Medical School at Houston
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Sugar Land
country: United States
facility: Gulf Coast Medical Research, LLC
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: Salt Lake City
country: United States
facility: Highland Clinical Research
state: Utah
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Chester
country: United States
facility: Khan and Abbasi Research
state: Virginia
city: Richmond
country: United States
facility: Healing Hands of Virginia LLC
state: Virginia
city: Virginia Beach
country: United States
facility: Gastroenterology Consultants
state: Virginia
city: Richland
country: United States
facility: ZainResearch, LLC
state: Washington
city: Brussels
country: Belgium
facility: Hopital Erasme - Universite Libre de Bruxelles
city: Leuven
country: Belgium
facility: UZ Leuven
city: Bad Oeynhausen
country: Germany
facility: Herz und Diabeteszentrum Nordrhein Westfalen, Universitätsklinikum der Ruhr-Universiät Bochum
city: Dippoldiswalde
country: Germany
facility: Praxis Dr. Ott Rabenauer Str.
city: Dresden
country: Germany
facility: GWT-TUD GmbH
city: Hamburg
country: Germany
facility: Israelitisches Krankenhaus Orchideenstig
city: Mainz
country: Germany
facility: Diabetes Zentrum und Praxis Prof. Pfützner Parcusstr.
city: Haifa
country: Israel
facility: Rambam Health Care Campus - Inst. of Endocrinology, Diabetes, and Metabolism
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital Gastroenterology Dept
city: Safed
country: Israel
facility: ZIV Medical Center
city: Bialystok
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorób Kostno-Stawowych J. Badurski S.J. ul.
city: Kielce
country: Poland
facility: NZOZ Witamed al.
city: Krakow
country: Poland
facility: CenterMed Krakow
city: Lodz
country: Poland
facility: Gabinet Lekarski dr n.med. Malgorzata Saryusz-Wolska ul.
city: Lodz
country: Poland
facility: NZOZ Pulsmedica ul.
city: Staszów
country: Poland
facility: KO-MED Centra Kliniczne
city: Warszawa
country: Poland
facility: Centrum Badawcze Wspólczesnej Terapii ul.
city: Warszawa
country: Poland
city: Stockholm
country: Sweden
facility: Gastroenterology Karolinska University Hospital Karolinska Universitetssjukhuset Gastro Centrum Medicine
city: Uppsala
country: Sweden
facility: Uppsala University Hospital Gastroenterology / Mag-Tarmmottagningen ingang
city: Dundee
country: United Kingdom
facility: NHS Tayside
state: Scotland
city: Ashington
country: United Kingdom
facility: Wansbeck General Hospital (Northumbria NHS Trust)
city: Durham
country: United Kingdom
facility: University Hospital of North Durham University Hospital of North Durham Research and Development Directorate
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
city: Tyne And Wear
country: United Kingdom
Study officials:
affiliation: Allergan
name: Wieslaw Bochenek, MD
role: STUDY_DIRECTOR
References:
citation: Camilleri M, Lembo A, McCallum R, Tourkodimitris S, Kemps L, Miller MB, Bertelsen K, Iacob A. Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data. Aliment Pharmacol Ther. 2020 Jun;51(11):1139-1148. doi: 10.1111/apt.15711. Epub 2020 Apr 17.
citation: Camilleri M, McCallum RW, Tack J, Spence SC, Gottesdiener K, Fiedorek FT. Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study. Gastroenterology. 2017 Nov;153(5):1240-1250.e2. doi: 10.1053/j.gastro.2017.07.035. Epub 2017 Jul 29.