A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis Study 04

Study Overview
=================
Brief Summary
-----------------
A 52-week study to compare the efficacy of relamorelin with that of placebo in participants with diabetic gastroparesis (DG) with respect to the core signs and symptoms of diabetic gastroparesis.

Official Title
-----------------
A 52-week, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis

Conditions
-----------------
Gastroparesis, Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Relamorelin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Two different groups of participants may enter into the study: Rollover Participants Participants who were not randomization-eligible at the end of the Run-in Period of lead-in studies RLM-MD-01 (NCT03285308) or RLM-MD-02 (NCT03426345) 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 Diabetic Gastroparesis Symptom Severity Diary (DGSSD)) except that: They had zero vomiting episodes and an average daily Diabetic Gastroparesis Symptom Severity Score (DGSSS) of ≥12 at the end of the lead-in study Run-in Period, as reported using the electronic hand-held device; OR 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 Type 1 Diabetes Mellitus (T1DM) or Type 2 Diabetes Mellitus (T2DM) of at least 5 years' duration, with controlled and stable blood glucose levels and hemoglobin A1c (HBA1c) ≤11% DG defined as at least a 3-month history prior to Screening of symptoms (one of which must be nausea) on an ongoing basis that are suggestive of gastroparesis (GP) (e.g., nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety) Compliance with the entry of data into the hand-held electronic device during the Run-in Period Compliance with administration of subcutaneous (SC) twice daily injections during the Run-in Period The average of the daily DGSSS from the 2-week, Run-in Period must be ≥12 Exclusion Criteria: Both Rollover and De Novo Participants •Participants with a known allergy or hypersensitivity to the study treatments and their excipients (i.e., mannitol or phenol) Rollover Participants •Participants will be excluded from this study if any of the lead-in study exclusion criteria apply at the Screening Visit and at the end of the Run-in Period 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 History of anorexia nervosa, binge-eating, bulimia, or other eating disorder within 5 years of the Screening Visit History of intestinal malabsorption or pancreatic exocrine insufficiency History of belching disorders, other nausea and vomiting disorders Gastric or duodenal ulcer within 3 months of Screening History of malignancy in the 3 years prior to Screening, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube for feeding or decompression Use of metoclopramide, domperidone, prucalopride, macrolide antibiotics (e.g., erythromycin, clarithromycin, azithromycin), or other drugs considered to be GI promotility agents for at least 10 days prior to the start of the Run-in Period Currently taking opiates, or expecting to use opiates during the course of the clinical study Treatment with glucagon-like peptide-1 (GLP-1) agonist for at least 6 weeks prior to the start of the Run-in Period History of pyloric injection of botulinum toxin within 6 months of screening History of gastric surgery such as fundoplication, gastrectomy, gastric pacemaker placement, vagotomy, or bariatric procedure (a history of diagnostic endoscopy is not exclusionary) Randomization in any previous study in which relamorelin was a treatment Allergic to, or intolerant of egg, wheat, milk, or algae, as these are components of the gastric emptying breath test (GEBT) study meal

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in. | Drug: Placebo<br>* Placebo injected subcutaneously twice daily.<br>|
| Experimental: Relamorelin 10 μg<br>Relamorelin 10 micrograms (μg) injected subcutaneously twice daily for up to 52 weeks. De novo (New) participants, who did not participate in the previous relamorelin studies, began the study with a 2-week placebo run-in. | Drug: Relamorelin<br>* Relamorelin 10 μg injected subcutaneously twice daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS) | Participants assessed the severity of diabetic gastroparesis symptoms daily using the Diabetic Gastroparesis Symptom Severity Diary (DGSSD), recorded in an electronic diary (e-diary). The DGSSS was derived as the sum of the weekly averages of the 4 DGSSD items: nausea, abdominal pain, postprandial fullness and bloating. Each symptom was scored using an 11-point ordinal scale where: 0=no or not at all uncomfortable to 10=worst possible or most uncomfortable for a total possible DGSSS of 0 (best) to 40 (worst). A negative change from Baseline indicates improvement. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period of the previous study or the run-in period of this study for new participants. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02 for rollover participants or Day -14 to Day -1 for new participants) to Week 12 of this study | 
| Change From Baseline to Week 52 in the Weekly Average DGSSS | Participants assessed the severity of diabetic gastroparesis symptoms daily using the DGSSD, recorded in an electronic diary (e-diary). The DGSSS was derived as the sum of the weekly averages of the 4 DGSSD items: nausea, abdominal pain, postprandial fullness and bloating. Each symptom was scored using an 11-point ordinal scale where: 0=no or not at all uncomfortable to 10=worst possible or most uncomfortable for a total possible DGSSS of 0 (best) to 40 (worst). The average weekly scores at Week 52 were the average of the DGSSS scores from Week 49 to Week 52. A negative change from Baseline indicates improvement. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period of the previous study or the run-in period of this study for new participants. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02 for rollover participants or Day -14 to Day -1 for new participants) to Week 52 of this study | 
| Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAE) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is an AE that begins or worsens after receiving study drug. | First dose of study drug to within 30 days of the last dose of study drug (Up to approximately 56 weeks) | 
| Number of Participants With Potential Clinically Significant (PCS) Clinical Laboratory Results | Clinical Laboratory tests included Hematology, Chemistry and Urinalysis tests. The investigator determined if the results were clinically significant. Only those categories where at least 1 participant had a non-PCS value at Baseline and met the PCS criterion at least once during postbaseline are reported. | Up to 52 weeks | 
| Number of Participants With Clinically Meaningful Trends for Vital Signs | Vital Signs included assessments of heart rate, respiratory rate, systolic and diastolic blood pressure, and body temperature. The investigator determined if the abnormal results were clinically significant. | Up to 52 weeks | 
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results | A standard 12-lead ECG was performed. The investigator determined if the abnormal results were clinically significant. | Up to 52 weeks | 
| Number of Participants With a ≥1% Increase in Glycosylated Hemoglobin A1c (HbA1c) |  | Up to 52 weeks | 
| Number of Participants With Anti-relamorelin Antibody Testing Results by Visit | A blood sample was collected that was sent to a laboratory for an anti-relamorelin antibody screening test. A positive screening test was confirmed by an immunodepletion assay. The number of participants in each of the following categories are reported: Negative Screening Test, Positive Screening Test, Negative Confirmatory Test, and Positive Confirmatory Test at each time point. | Baseline (Day 1), Day 84, Day 364, and End of Treatment (Up to Day 364) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diabetic gastroparesis, vomiting