Vomiting symptoms in patient with moderate to severe diabetic gastroparesis MedDRA version: 17.1 Level: PT Classification code 10051153 Term: Diabetic gastroparesis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: Relamorelin
Product Code: RM-131
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: None
CAS Number: 945416-05-7
Current Sponsor code: RM-131
Other de
Sponsors
Rhythm Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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). • Evaluate the effect of RM-131 on vomiting severity (as assessed in the DGSSD). • Evaluate the effect of RM-131 on gastric emptying (GE).;Primary end point(s): The primary efficacy endpoint is: • 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoint is: • Longitudinal analysis of changes from baseline over time in weekly averages of the 4 individual daily symptom scores (e.g., the 4 subjective symptoms) using a global statistic. Secondary efficacy endpoints are: • Longitudinal analysis of changes from baseline over time in weekly average of the 4- symptom composite of subjective symptoms of DG (nausea, early satiety, bloating, and epigastric or abdominal pain). • Longitudinal analysis of weekly average vomiting episodes. • Longitudinal analysis of changes from baseline over time in weekly averages of the other individual daily symptom scores (e.g., the 4 subjective symptoms). • Longitudinal analysis of changes from baseline over time in weekly averages of vomiting severity. • Longitudinal analysis of changes from baseline over time in weekly averages of the 5 individual daily symptom scores (e.g., the 4 subjective symptoms and vomiting endpoints) using a global statistic. • Gastric emptying as measured by the GEBT half-time. Other tertiary and exploratory endpoints will include PK, PK/PD, weight, glucose, and analysis of different global statistical approaches. Effects of RM-131 on symptoms of gastroparesis will be evaluated using the DGSSD. Exploratory assessments of symptoms may also utilize Symptom and Global Assessment data. Safety endpoints include: • Physical examination, including assessment of the injection site, weight and vital signs • Clinical laboratory safety tests: • Complete blood count (CBC) with automated differential • Chemistry panel (including sodium, potassium, chloride, carbon dioxide (CO2), albumin, glucose, calcium, total protein, aspartate aminotransferase (AST), ALT, GGT, creatine kinase (CK), alkaline phosphatase, total bilirubin, direct bilirubin, blood urea nitrogen (BUN), creatinine, uric acid, lactate dehydrogenase (LDH), cholesterol and triglycerides. (Procedures for follow-up of abnormal liver function tests are provi | — |
Countries
Belgium, Germany, Israel, Poland, Sweden, United Kingdom, United States
Contacts
Public ContactInformation
Rhythm Pharmaceuticals, Inc.
Outcome results
None listed