Safety and Efficacy of Relamorelin Administered to Participants With Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis
Condition: Diabetes Mellitus; Diabetes Mellitus Complications; Gastroparesis
MeSH terms: Gastroparesis; Diabetes Mellitus; Diabetes Complications; Vomiting
Intervention: Relamorelin; Placebo
Intervention description: Double blind relamorelin was given subcutaneously BID for 12 weeks.; Placebo given subcutaneously for 12 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 393.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus; Delayed Gastric Emptying; Vomiting; Gastroparesis; Gastrointestinal Motility Disorder

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.