A 52-week Study to Evaluate the Safety and Efficacy of Relamorelin in Patients with Diabetic Gastroparesis

Phase 1

• Conditions: Diabetic Gastroparesis; MedDRA version: 20.1Level: PTClassification code 10051153Term: Diabetic gastroparesisSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2017-002144-33-BG
• Lead Sponsor: Allergan Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-09-18
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

Rollover Participants:
Participants who were not randomization-eligible at the end of the Run-in Period of lead-in Studies RLM-MD-01 or RLM-MD-02 are eligible to be randomized in the study if all of the following criteria apply:
In the lead-in studies, participants must have met all Screening Visit and Run-in Period criteria for randomization into the Treatment Period (including compliance with dosing, entry of diary data into the DGSSD) except that:
1. They had zero vomiting episodes and an average daily DGSSS of = 12 at the end of the lead-in study Run-in Period, as reported using the electronic hand-held device;
OR
2. They had vomiting episodes and an average daily DGSSS of = 12 but < 16 at the end of the lead-in study Run-in Period, as reported using the electronic hand-held device.

De Novo Participants
Participants who undergo screening and run-in procedures for Study RLM MD-04 are eligible to be included in the study if all of the following criteria apply:
1. Male or female participants aged 18 years or older at Screening (Visit –2)
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 –2])
3. HbA1c = 11.0% at Screening (Visit –2) 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 –2) of symptoms (one of which must be nausea) on an ongoing basis that are suggestive of GP (eg, nausea, abdominal pain, postprandial 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 endoscopy or other equivalent diagnostic test, performed at some time before Screening (Visit –2) but after the appearance of symptoms that led to the diagnosis of DG
7. Nausea and/or at most a single episode of vomiting during the 2 weeks prior to Screening (Visit –2), 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 of RLM-MD-01, RLM-MD-02, or this study). 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. BMI > 18.5 kg/m2
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 Run-in Period
12. Compliance with administration of SC twice daily injections, as evid

Exclusion Criteria

Rollover Participants
Participants will be excluded from this study if any of the lead-in study exclusion criteria apply at Screening (Visit 1) and at the end of the Run-in Period (Visit 3) for randomization into the Treatment Period of Studies RLM MD 01 and RLM MD-02, except as specified in the inclusion criteria
De Novo Participants
1. Symptomatic Irritable Bowel Syndrome at Screening (Visit –2)
2. Small intestinal bacterial overgrowth (SIBO) at Screening (Visit –2)
3. History of anorexia nervosa, binge-eating, bulimia, or other eating disorder within 5 years of Screening (Visit –2)
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 at Screening (Visit 2)
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), 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 –1)
12. Positive results on the urine drug screen will exclude participants from participating in the study. The significance of a positive screen result for drugs prescribed for the participant (eg, barbiturates, benzodiazepines, amphetamines, but not 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 drugs on an as-needed basis is not allowed
13. Currently taking opiates, or expecting to use opiates 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 –1)
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 of egg, wheat, milk, or algae, as these are components of the GEBT study meal
21. Females who are pregnant, nursing, or planning a pregnancy during the study
22. The participant has a condition or is in a situation which, in the investigator’s opinion, may put the participant at significant risk, ma

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To compare the efficacy of relamorelin with that of placebo in participants with DG with respect to: DGSSS, Individual symptoms of DGSSS (Nausea, Abdominal pain, Postprandial fullness, Bloating), Vomiting Frequency<br>;Secondary Objective: - To compare the safety of relamorelin with that of placebo in participants with DG;Primary end point(s): - DGSSS Week 12 Responder<br>- Vomiting Frequency Week 12 Responder <br>- DGSSS Week 52 Responder<br>- Vomiting Frequency Week 52 Responder <br>- Nausea Week 12 Responder<br>- Abdominal Pain Week 12 Responder<br>- Bloating Week 12 Responder<br>- Postprandial Fullness Week 12 Responder<br>- Change from baseline to Week 52 in average weekly DGSSS<br>- Change from baseline to Week 52 in average weekly number of vomiting episodes<br>;Timepoint(s) of evaluation of this end point: - week 12<br>- week 52

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Adverse events (AEs), clinical laboratory values, vital signs, electrocardiograms (ECGs), hemoglobin A1c (HbA1c), and anti-relamorelin antibodies;Timepoint(s) of evaluation of this end point: The whole study duration