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

• Placebo (Drug): Placebo injected subcutaneously twice daily.
• Relamorelin (Drug): Relamorelin 10 μg injected subcutaneously twice daily.

Primary outcomes

• Change From Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS) [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]: 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.
• Change From Baseline to Week 52 in the Weekly Average DGSSS [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]: 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.
• Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAE) [First dose of study drug to within 30 days of the last dose of study drug (Up to approximately 56 weeks)]: 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.
• Number of Participants With Potential Clinically Significant (PCS) Clinical Laboratory Results [Up to 52 weeks]: 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.
• Number of Participants With Clinically Meaningful Trends for Vital Signs [Up to 52 weeks]: 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.
• Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results [Up to 52 weeks]: A standard 12-lead ECG was performed. The investigator determined if the abnormal results were clinically significant.
• 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 [Baseline (Day 1), Day 84, Day 364, and End of Treatment (Up to Day 364)]: 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.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Two different groups of participants may enter into the study:

1. 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
2. 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:

1. 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)
2. 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
3. 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

Participant flow

Outcome results

• Change From Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS) (Primary), Mean, score on a scale: Placebo 20.3 +/- 6.70; Relamorelin 10 μg 19.7 +/- 6.39
• Change From Baseline to Week 52 in the Weekly Average DGSSS (Primary), Mean, score on a scale: Placebo 20.3 +/- 6.70; Relamorelin 10 μg 19.7 +/- 6.39
• Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAE) (Primary), Count of participants, Participants: Placebo 105; Relamorelin 10 μg 221
• Number of Participants With Potential Clinically Significant (PCS) Clinical Laboratory Results (Primary), Count of participants, Participants: Placebo 0; Relamorelin 10 μg 1
• Number of Participants With Clinically Meaningful Trends for Vital Signs (Primary), Count of participants, Participants: Placebo 0; Relamorelin 10 μg 0
• Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Results (Primary), Count of participants, Participants: Placebo 2; Relamorelin 10 μg 2
• Number of Participants With a ≥1% Increase in Glycosylated Hemoglobin A1c (HbA1c) (Primary), Count of participants, Participants: Placebo 94; Relamorelin 10 μg 246
• Number of Participants With Anti-relamorelin Antibody Testing Results by Visit (Primary), Count of participants, Participants: Relamorelin 10 μg 127

Adverse events

Time frame: First dose of study drug to within 30 days of the last dose of study drug (Up to approximately 56 weeks)

Serious adverse events by term

23 more terms not shown.

Other adverse events by term

249 more sites not listed.

• Study Protocol (PDF, 2021-02-12)
• Statistical Analysis Plan (PDF, 2020-12-15)

• Harvy Schneier, Study director, Allergan

NIH grants: 2017