A controlled clinical trial to study RM-131 (relamorelin) in patients with vomiting symptoms and diabetic gastroparesis
- Conditions
- Vomiting symptoms in patient with moderate to severe diabetic gastroparesisMedDRA version: 17.1Level: PTClassification code 10051153Term: Diabetic gastroparesisSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2014-005623-27-BE
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 395
1. T1DM or T2DM with stable glycemic control and HbA1c =11% at screening.
2. 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).
3. GCSI-DD score =2.6 at least once during the Screening Period (Visits 1-2).
4. At least 2 vomiting episodes during the ~2 weeks prior to the first screening visit (Visit 1), as ascertained by patient history.
5. Delayed GE confirmed at screening by abnormal GEBT (AB Diagnostics), 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).
6. 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).
7. No use of metoclopramide, erythromycin, domperidone, or other 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.
8. Body mass index >18 kg/m2.
9. 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 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).
10. 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:
11. Compliance with the completion of the 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).
12. At least one vomiting episode at any time during the 2-week single-blind placebo run-in period, as recorded in the DGSSD.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1. Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube for feeding or decompression.
2. History of gastric surgery such as fundoplication, gastrectomy, gastric pacemaker placement, vagotomy, or bariatric procedure. (A history of diagnostic endoscopy is not exclusionary.)
3. History of pyloric injection of botulinum toxin within 6 months of screening.
4. 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.
5. Currently taking opiates, or expecting to use opiates during the course of the clinical trial.
6. Currently taking GLP-1 agonists, SGLT2 inhibitors or pramlintide.
7. Allergic or intolerant of egg, wheat, milk, or algae, as these are components of the GEBT study meal. (Gluten-free crackers can be provided.)
8. History of anorexia nervosa, binge-eating, or bulimia within 5 years of screening.
9. ALT or AST > 2 × upper limit of normal (ULN) at Visit 1.
10. History of intestinal malabsorption or pancreatic exocrine disease.
11. Requires hemodialysis or has end-stage renal disease.
12. History of human immunodeficiency virus (HIV) infection.
13. Clinically significant neurologic or psychiatric disorders that are likely to impact compliance with protocol requirements.
14. Poor venous access or inability to tolerate venipuncture.
15. Participation in a clinical study within the 30 days prior to dosing in the present study.
16. 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 ECG abnormalities.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • Evaluate the effect of RM-131 on vomiting episodes in patients with diabetic gastroparesis (DG).;Secondary Objective: • Evaluate the effects of RM-131 on 4 key symptoms of gastroparesis (nausea, early satiety, bloating, and abdominal pain) assessed with a composite score derived from the Diabetic Gastroparesis Symptom Severity Diary (DGSSD).<br>• Evaluate the effect of RM-131 on vomiting severity (as assessed in the DGSSD).<br>• Evaluate the effect of RM-131 on gastric emptying (GE).;Primary end point(s): The primary efficacy endpoint is:<br>• Longitudinal analysis of the number of weekly vomiting episodes, averaged across the 12-week treatment period.;Timepoint(s) of evaluation of this end point: Weekly
- Secondary Outcome Measures
Name Time Method