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

July 1, 2019 updated by: Allergan

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

393

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 12 in Weekly Vomiting Episodes
Time Frame: 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.
7 days prior to Day 1 for Baseline to 7 days prior to Week 12

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Allergan

Investigators

  • Study Director: Wieslaw Bochenek, MD, Allergan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2015

Primary Completion (Actual)

June 9, 2016

Study Completion (Actual)

June 9, 2016

Study Registration Dates

First Submitted

January 29, 2015

First Submitted That Met QC Criteria

February 5, 2015

First Posted (Estimate)

February 6, 2015

Study Record Updates

Last Update Posted (Actual)

July 24, 2019

Last Update Submitted That Met QC Criteria

July 1, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RM-131-009
  • 2014-005623-27 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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