A Safety and Efficacy Study of Relamorelin in Diabetic Gastroparesis Study 03

Study Overview
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Brief Summary
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A 46-week study to compare the efficacy of relamorelin with that of placebo in participants with diabetic gastroparesis (DG). At the end of the 40-week Treatment Period, participants will either continue on relamorelin or placebo for 6 additional weeks.

Official Title
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A 46-week, Double-blind, Placebo-controlled, Phase 3 Study With a 6-week Randomized-withdrawal Period to Evaluate the Safety and Efficacy of Relamorelin in Patients With Diabetic Gastroparesis

Conditions
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Gastroparesis, Diabetes Mellitus

Intervention / Treatment
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* Drug: Placebo
* Drug: Relamorelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are eligible to be included in the study only if all the following criteria apply: Participant met all inclusion/exclusion criteria of either Protocol RLM-MD-01 (NCT03285308) or Protocol RLM-MD-02 (NCT03426345) and successfully completed the study Able to provide written informed consent (IC) prior to any study procedures and willing and able to comply with study procedures In the opinion of the investigator, the participant demonstrated adequate compliance with the study procedures in Study RLM-MD-01 or RLM-MD-02 Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Participant is not willing or able to abide by the restrictions regarding concomitant medicine use Participant is planning to receive an investigational drug (other than study treatment) or investigational device at any time during Study RLM-MD-03 Participant has an unresolved adverse event (AE) or a clinically significant finding on physical examination, clinical laboratory test, or 12-lead electrocardiogram (ECG) that, in the investigator's opinion, would limit the participant's ability to participate in or complete the study Any other reason that, in the investigator's opinion, would confound proper interpretation of the study or expose a participant to unacceptable risk, including renal, hepatic or cardiopulmonary disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment Period: Placebo<br>Placebo-matching relamorelin injected subcutaneously twice daily for up to 40 weeks. | Drug: Placebo<br>* Placebo injected twice daily<br>|
| Experimental: Treatment Period: Relamorelin 10 μg<br>Relamorelin 10 micrograms (μg) injected subcutaneously twice daily for up to 40 weeks. | Drug: Relamorelin<br>* Relamorelin 10 μg injected twice daily<br>|
| Experimental: Randomized Withdrawal Period: Placebo then Relamorelin 10 μg<br>Participants who received placebo-matching relamorelin injected subcutaneously twice daily for 40 weeks, followed by relamorelin 10 μg injected twice daily for up to 6 weeks in the Randomized Withdrawal (RW) Period. | Drug: Placebo<br>* Placebo injected twice daily<br>Drug: Relamorelin<br>* Relamorelin 10 μg injected twice daily<br>|
| Experimental: Randomized Withdrawal Period: Relamorelin 10 μg then Relamorelin 10 μg<br>Participants who received relamorelin 10 μg injected subcutaneously twice daily for 40 weeks, followed by relamorelin injected twice daily for up to 6 weeks in the RW Period. | Drug: Relamorelin<br>* Relamorelin 10 μg injected twice daily<br>|
| Experimental: Randomized Withdrawal Period: Relamorelin 10 μg then Placebo<br>Participants who received relamorelin 10 μg injected subcutaneously twice daily for 40 weeks, followed by placebo-matching relamorelin injected twice daily for up to 6 weeks in the RW Period. | Drug: Placebo<br>* Placebo injected twice daily<br>Drug: Relamorelin<br>* Relamorelin 10 μg injected twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in the Weekly Diabetic Gastroparesis Symptom Severity Score (DGSSS) of the Treatment Period | 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 in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to Week 12 of this study | 
| Percentage of Participants Meeting the Vomiting Responder Criterion During Each of the Last 6 Weeks of the First 12-weeks of the Treatment Period | The number of vomiting episodes in the previous 24 hours were assessed daily by the participant using the DGSSD and were recorded in the e-diary. A Vomiting Responder was defined as a participant with zero weekly vomiting episodes during each of the last 6 weeks of the first 12-weeks of the 40-week Treatment Period. | Week 6 to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Meeting the Nausea Responder Criterion During Each of the Last 6 Weeks of the First 12-weeks of the Treatment Period | A Nausea Responder was defined as a participant with improvement (decrease) of at least 2-points in the weekly symptom scores for nausea at each of the last 6 weeks of the first 12-weeks of the 40-week Treatment Period. Nausea was one of the items of the DGSSD assessed daily and recorded in the e-diary by the participant using an 11-point ordinal scale where: 0=no nausea to 10=worst possible nausea. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 6 to Week 12) | 
| Percentage of Participants Meeting the Abdominal Pain Responder Criterion During Each of the Last 6 Weeks of the First 12-weeks of the Treatment Period | An Abdominal Pain Responder was defined as a participant with an improvement (decrease) of at least 2-points in the weekly symptom scores for abdominal pain at each of the last 6 weeks of the first 12-weeks of the 40-week Treatment Period. Abdominal pain was one of the items of the DGSSD assessed daily and recorded in the e-diary by the participant using an 11-point ordinal scale where: 0=no abdominal pain to 10=the worst possible abdominal pain and was recorded in an e-diary. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 6 to Week 12) | 
| Percentage of Participants Meeting the Bloating Responder Criterion During Each of the Last 6 Weeks of the First 12-weeks of the Treatment Period | A Bloating Responder was defined as a participant with an improvement (decrease) of at least 2-points in the weekly symptom scores for bloating at each of the last 6 weeks of the first 12-weeks of the 40-week Treatment Period. Bloating was one of the items of the DGSSD assessed daily and recorded by the participant in the e-diary using an 11-point ordinal scale where: 0=no bloating and 10=the worst possible bloating and was recorded in the e-diary. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 6 to Week 12) | 
| Percentage of Participants Meeting the Postprandial Fullness Responder Criterion During Each of the Last 6 Weeks of the First 12-weeks of the Treatment Period | A Postprandial Fullness Responder was defined as a participant with an improvement (decrease) of at least 2-points in the weekly symptom scores for Postprandial Fullness at each of the last 6 weeks of the first 12-weeks of the 40-week Treatment Period. Postprandial Fullness was one of the items of the DGSSD assessed daily and recorded by the participant in the e-diary using an 11-point ordinal scale where: 0=no feeling of fullness until finishing a meal (best) to 10=feeling full after only a few bites (worst). Baseline was defined as the average of the 2 weekly DGSSS from the run-in period in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 6 to Week 12) | 
| Change From Baseline to Week 40 in the Average Weekly DGSSS of the Treatment Period | Participants assessed the severity of diabetic gastroparesis symptoms daily using the DGSSD, recorded in an e-diary. The DGSSS was derived as the sum of the weekly averages (Week 37 to Week 40) 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 studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 37 to Week 40) | 
| Percentage of Participants Meeting the Vomiting Responder Criterion at Week 40 of the Treatment Period | The number of vomiting episodes in the previous 24 hours were assessed daily by the participant using the DGSSD and were recorded in the e-diary. A Vomiting Responder was defined as a participant with zero weekly vomiting episodes during the last 4 weeks of the 40-week Treatment Period. | Week 37 to Week 40 | 
| Change From Baseline to Week 40 in the Average Weekly Number of Vomiting Episodes of the Treatment Period | The number of vomiting episodes in the previous 24 hours were assessed daily by the participant using the DGSSD and were recorded in the e-diary. The average weekly number of vomiting episodes were derived as the average of the weekly number of vomiting episodes in the last 4 weeks of the 40-week Treatment Period. A negative change from Baseline indicates improvement. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 37 to Week 40) | 
| Change From Baseline to Week 46 in the Average Weekly DGSSS of the Randomized-Withdrawal Period | Participants assessed the severity of diabetic gastroparesis symptoms daily using the DGSSD, recorded in an 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). Average weekly scores are derived as the average of the weekly scores from the 6 weeks of the RW Period. A negative change from Baseline indicates improvement. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 41 to Week 46) | 
| Change From Baseline to Week 46 in the Average Weekly Number of Vomiting Episodes of the Randomized-Withdrawal Period | The number of vomiting episodes in the previous 24 hours were assessed daily by the participant using the DGSSD and were recorded in the e-diary. Average weekly number of vomiting episodes are derived as the average of the weekly number of vomiting episodes from the six weeks of the RW Period. A negative change from Baseline indicates improvement. Baseline was defined as the average of the 2 weekly DGSSS from the run-in period in the previous studies. | Baseline (14-day Run-in Period of the previous relamorelin study RLM-MD-01 or RLM-MD-02) to (Week 41 to Week 46) | 
| 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 50 weeks) | 
| Number of Participants With Potential Clinically Significant (PCS) Clinical Laboratory Results | Clinical Laboratory values included Hematology, Chemistry and Urinalysis tests. The investigator determined if the results were clinically significant. Only those categories where at least 1 person had a non-PCS value at Baseline and met the PCS criterion at least once during postbaseline are reported. | Up to 46 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 results were clinically significant. | Up to 46 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 46 weeks | 
| Number of Participants With a ≥1% Increase in Glycosylated Hemoglobin A1c (HBA1c) |  | Up to 46 weeks | 
| Number of Participants With Anti-relamorelin Antibody Testing Results | 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. | Up to 46 weeks | 

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