Diabetic Gastroparesis MedDRA version: 20.1 Level: PT Classification code 10051153 Term: Diabetic gastroparesis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Sponsors
Allergan Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants aged 18 years or older at screening (Visit 1) 2. T1DM or T2DM of at least 5 years’ duration, with controlled and stable blood glucose levels (ie, no episodes of diabetic ketoacidosis, Hyperosmolar Hyperglycemic Nonketotic Diabetic Syndrome, or severe hypoglycemia within the 6 months preceding screening [Visit 1]) 3. HbA1c =11.0% at screening (Visit 1) in participants being treated with oral and/or parenteral medications for T1DM or T2DM with the goal of achieving controlled and stable glucose levels 4. DG defined as at least a 3-month history prior to screening (Visit 1) of symptoms on an ongoing basis that are suggestive of GP (eg, nausea, abdominal pain, post-prandial fullness, bloating, vomiting, and early satiety) 5. Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period A female participant is eligible to participate if she is not pregnant (has a negative urine pregnancy result prior to randomization), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) OR b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 7 days after the last dose of study treatment 6. Documentation of absence of an obstructing lesion on upper GI series with contrast or upper endoscopy performed at some time before the Run-in Period (Visit 2) but after the appearance of symptoms that led to the diagnosis of DG 7. At least 2 vomiting episodes during the 2 weeks prior to screening (Visit 1), as ascertained by participant history 8. Delayed GE confirmed by abnormal GEBT, defined as GE half-time (t½) = 79 minutes at the start of the placebo-controlled Run-in Period (Visit 2). In countries where the GEBT is not available, delayed GE may be confirmed by abnormal scintigraphy result (> 60% retention at 2 hours or > 10% at 4 hours) 9. The BMI criterion has been removed. 10. Able to provide written informed consent (IC) prior to any study procedures and willing and able to comply with study procedures Additional inclusion criteria for randomization after the 2-week, placebo Run-in Period: 11. Compliance with the entry of data into the hand-held electronic device on at least 10 of 14 days during the placebo Run-in Period 12. Compliance with administration of SC twice daily injections, as evidenced by entries made by the participant using the electronic, hand-held device on at least 10 of 14 days during the placebo Run-in Period 13. At least one vomiting episode at any time during the placebo Run-in Period, as recorded in the DGSSD, using the electronic hand-held device 14. The average of the daily DGSSS from the 2-week, placebo Run-in Period must be = 16 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 1875 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 625
Exclusion criteria
Exclusion criteria: 1. Symptomatic Irritable Bowel Syndrome at Screening (Visit 1) 2. Small intestinal bacterial overgrowth (SIBO) at Screening (Visit 1) 3. Participants who are actively experiencing anorexia nervosa, binge-eating, bulimia, or other eating disorder at the time of Screening (Visit 1) are excluded regardless of when diagnosis was established. 4. History of intestinal malabsorption (including celiac disease even if well-controlled on a gluten-free diet) or pancreatic exocrine insufficiency; also, history of non-celiac gluten sensitivity 5. History of belching disorders, other nausea and vomiting disorders (eg, chronic nausea and vomiting syndrome, cyclic vomiting syndrome, cannabinoid hyperemesis syndrome), or rumination syndrome 6. History of chronic obstructive pulmonary disease or other causes of pulmonary dysfunction that have resulted in CO2 retention 7. Gastric or duodenal ulcer within 3 months of Screening (Visit 1) 8. Evidence of hepatic disease defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 3 x ULN, and/or direct bilirubin = 2 x ULN 9. History of malignancy in the 3 years prior to Visit 1, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer 10. Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube for feeding or decompression 11. Use of metoclopramide, domperidone, prucalopride, macrolide antibiotics (eg, erythromycin, clarithromycin, azithromycin), 5HT4 agonists (cisapride, tegaserod, and prucalopride) or other drugs considered to be GI pro-motility agents for at least 10 days prior to the start of the Run-in Period (Visit 2) 12. Positive results on the urine drug screen at Screening (Visit 1). The sponsor may permit a participant with a positive urine drug screen by immunoassay at Screening to continue in screening while confirmatory testing by a more specific method is carried out on an aliquot of the original urine sample. If the confirmatory test is negative, the initial positive UDS will be considered to have been a false-positive urine drug screen and the participant can continue in screening. Confirmatory testing will be done at the discretion of the sponsor and must be approved by the sponsor prior to analysis. The significance of a positive urine drug screen result for drugs prescribed for the participant (ie, barbiturates, benzodiazepines, amphetamines, but not opioids or cannabinoids) should be assessed by the Investigator as to whether their stable-dose usage is clinically appropriate, and, therefore, should not be exclusionary; use of these prescribed drugs on an as-needed basis is not allowed 13. Currently taking opioids, or expecting to use opioids during the course of the clinical study 14. Treatment with glucagon-like peptide-1(GLP-1) agonist for at least 6 weeks prior to the start of the Run-in Period (Visit 2) 15. History of pyloric injection of botulinum toxin within 6 months of screening 16. History of gastric surgery such as fundoplication, gastrectomy, gastric pacemaker placement, vagotomy, or bariatric procedure (a history of diagnostic endoscopy is not exclusionary) 17. Randomization in any previous study in which relamorelin was a treatment 18. Estimated glomerular filtration rate (eGFR) of < 30 mL/min 19. Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study 20. Allergic to, or intolerant o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare the efficacy of relamorelin with placebo in participants with DG with respect to a composite of the following core signs and symptoms of DG: Nausea, Abdominal pain, Postprandial fullness, Bloating - To compare the efficacy of relamorelin with placebo in participants with DG with respect to vomiting frequency ;Secondary Objective: - To compare the efficacy of relamorelin with placebo in participants with DG with respect to the following individual symptoms of the DGSSS: Nausea, Abdominal Pain, Postprandial fullness, Bloating - To compare the safety of relamorelin with placebo in participants with DG ;Primary end point(s): - Change from Baseline to Week 12 in the weekly DGSSS. Baseline is defined as the average of the 2 weekly DGSSS from the 2-week, placebo Run-in Period - Vomiting Responder, defined as a participant with zero weekly vomiting episodes during each of the last 6 weeks of the 12-week Treatment Period ;Timepoint(s) of evaluation of this end point: each of the last 6 weeks of the 12-week Treatment Period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Individual Symptom (ie, nausea, abdominal pain, postprandial fullness, and bloating) Responder, defined as a participant with at least a 2-point decrease in the change from baseline on the weekly average of the symptom severity (at its worst) during each of the last 6 weeks of the 12-week Treatment Period - AEs, clinical laboratory values, vital signs, ECGs, HbA1c, and anti-relamorelin antibodies ;Timepoint(s) of evaluation of this end point: each of the last 6 weeks of the 12-week Treatment Period | — |
Countries
Australia, Bulgaria, France, India, Israel, Italy, Korea, Republic of, Malaysia, Philippines, Poland, Saudi Arabia, Singapore, Spain, Thailand, Ukraine, United Arab Emirates
Contacts
Public ContactAllergan Ltd EU Regulatory Dept.
Allergan Ltd.
Outcome results
None listed