The following changes were implemented with Amendment 1: -Changed the definition of the diabetic gastroparesis symptom severity diary (DGSSS) score for responder (the primary endpoint) from ≥8 point improvement to a ≥10 point improvement -Added GE by gastric emptying breath test (GEBTs) to Visit 7 and the early termination Visit, and to adjust the schedule of assessment (SoA) footnote l to add GEBT to assessments performed on a subset of participants at a subset of sites -Revised the wording of inclusion criteria -Revised the order of the inclusion and exclusion criteria -Added an exclusion criterion for hepatic disease -Removed the exclusion for treatment with a sodium-glucose co-transporter 2 (SGLT-2) -Reordered the objectives and endpoints -Corrected the maximum volumes of blood drawn for the scheduled labs and for the pharmacokinetic (PK) and hormone subset -Moved the questions for Patient Global Impression of Status and Impression of Change -Added information on the GEBT analysis -Revised the washout requirements for SGLT-2 inhibitors from 2 weeks prior to the start of the Run-in Period to 3 days prior to the GEBT done at the start of Run-in Period -Revised the sample size determination -Updated the definition of the PK population -Updated the statistical methodology to remove unused methodologies and descriptions -Removed the Multiple Comparisons Procedures for the United States and European Union, and added sections on multiple comparisons procedure and missing data -Added a new section on major adverse cardiovascular events -Clarified Hy’s Law and adverse events of special interest (AESI) reporting.

The following changes were implemented with Amendment 2: -Removed glycated albumin from the safety endpoints and objectives and endpoints, and in the safety analyses -Increased the number of sites and participants screened -Moved no use of promotility agents and anti-emetics to after Run-in Period -Updated the SoA to add a new footnote (o) to PK samples at end of treatment (ET), to add fasting fingerstick glucose testing at Visit 7 and ET -Updated the SoA footnotes (f), (i). and (q) for clarity -Updated the SoA to add a new footnote (x) to inspect injection sites -Revised exclusion criterion -Inserted 2 new exclusion criteria -Revised treatments administered for clarity -Revised treatment compliance for clarity -Added text to concomitant therapy for clarity -Updated prohibited medications to clarify the use of anti-emetics, and to add an exception from the opioid prohibition -Updated rescue medicine to clarify the use of anti-emetics -Updated Patient Global Impression of Change-Diabetic Gastroparesis (PGIS-DG) for clarity -Updated major adverse cardiovascular events to define the required timing for reporting major adverse cardiovascular events (MACE) -Revised treatment of overdose for accuracy -Revise physical examinations for clarity -Updated PK to clarify PK draws at ET -Updated "Hommel test" was changed to "Holm test" -Updated clinical laboratory tests -Corrected the study title.

The following changes were implemented with Amendment 3: -Revised SoA footnote (a) to indicate early termination visit must be performed as soon as possible after decision has been made -Revised SoA footnote (i) to clarify details of urine drug screen results -Revised SoA footnote (m) to indicate pregnancy testing can be performed if required by local regulations -Revised inclusion criterion 3 to remove treatment requirement “for at least 3 months” for participants being treated with medications for diabetes mellitus type I (T1DM) or diabetes mellitus type II (T2DM) -Revised inclusion criterion to remove upper limit for body mass index (BMI) -Revised exclusion criterion to clarify that celiac disease even if well-controlled on gluten-free diet is exclusionary, and to add history of non-celiac gluten sensitivity as exclusionary -Revised Exclusion Criterion 5 to remove functional dyspepsia -Deleted exclusion criterion which addresses anemia, replacing it with a new exclusion criterion for gastric or duodenal ulcer within 3 months of screening -Revised exclusion criterion 9 to reduce history of malignancy from 5 to 3 years -Revised exclusion criterion to shorten exclusion period for promotility agents from 2 weeks to 10 days -Revised exclusion criterion to clarify details of urine drug screen results -Revised exclusion criterion to extend exclusion for use of glucagon-like peptide-1 (GLP-1) agonists to 6 weeks, and remove pramlintide.

-Revised exclusion criterion to remove the allowance for gluten-free crackers -Added exclusion criterion for functional dyspepsia diagnosed before diagnosis of diabetes mellitus -Revised screen failures to disallow rescreening after greater than 6 months -Revised Table 7-2 to shorten wash-out period for pro-motility agents, anticholinergics, anti-emetics, amylin analogue, and opioids from 2 weeks to 10 days prior to the start of Run-in Period; to extend exclusion for use of GLP-1 agonists from 2 to 6 weeks -Revised withdrawal from study to indicate ET Visit must be performed as soon as possible after the decision to discontinue has been made -Amended MACE text for clarity and to describe planned adjudication process -Added anti-relamorelin antibodies to other laboratory assessments in protocol-required safety laboratory assessments -Revised contraception guidance to add recommendations for acceptable birth control methods.

The following changes were implemented with Amendment 4: - Modified definition of primary endpoints - Increased number of sites from approximately 200 to approximately 350 Increased number of participants screened from 2000 to 2500 -Added requirement for study population at screening to have had a history of at least 2 vomiting episodes and to have had at least 1 vomiting episode during Run-in Period - Removed body mass index (BMI) information - Start of screening period was revised from Day -28 to Day -42 -Increased duration of Screening Visit from 14 days to 28 days. Updated study schematic to reflect change in length of Screening Visit -Increased duration of study from 16 weeks to 18 weeks and increased screening period from 2 weeks to up to 4 weeks -Added footnote (a) for screening Visit -Added electrocardiogram (ECG) obtained at Visit 4 -Amended footnote (j) -Removed assessment of glycated albumin from SOA and all related text -Added footnote for fasting blood glucose: Serum for all visits except for Visit 4 and 6 (plasma) -Removed year in all references to the relamorelin investigator brochure -Amended clinical hypotheses -Amended inclusion #6 to allow for a GI series with contrast as an assessment tool for documenting absence of an obstructing lesion and adjust timing of assessments from some time before screening (Visit 1) to sometime before the Run-in Period (Visit 2) -Removed BMI criterion #9 -Inclusion #10: added a reference to Appendix 3 -Amended exclusion #3 to specify that participants with active eating disorders at the time of screening are to be excluded, as opposed to those with a history of eating disorders -exclusion #11: Added 5HT agonists as exclusionary drug -Amended exclusion #12 to allow a participant with a positive urine drug screen at Screening to continue in study while confirmatory testing is done on an aliquot of original sample; specified that opioids are not drugs for which investigator may choose not to consider exclusionary.

-Added exclusion criteria for hypersensitivity to the study treatments and their excipients (Exclusion #25) and for specific corrected ECG results (Exclusion #26) -Added option for the sponsor to permit a participant with a positive urine drug screen at Screening to continue in the Screening Period while confirmatory urine drug screen testing by a more specific method is carried on an aliquot of the original sample -Clarified that the first dose of study treatment is to be administered within approximately 30 minutes before the morning meal and the second daily dose is to be administered within approximately 30 minutes before the evening meal -Deleted option for investigator to contact sponsor if the participant could not inject study treatment into abdomen -Unblinding procedures modified; requirement of investigator to notify sponsor prior to unblinding modified to encouraging the investigator to notify the sponsor prior to unblinding but requiring notification within 24 hours after breaking the blind -Removed: “non-compliance with study treatment” -Defined zero and 10 scores of the DG assessments -Changed Section 9.1.1.1 from diabetic gastroparesis symptom severity score (DGSSS) responder definition to Change from Baseline to Week 12 in the Weekly DGSSS -Revised assessment of DGSSS Weekly Scores -More assessments added in order to evaluate the additional endpoints -More assessments added in order to evaluate the additional endpoints -Added a row to describe Change from Baseline (CFB) -Updated primary endpoint and its description -Clarifications made to Hypothesis H1; reference made to SAP for other efficacy analyses -Added a requirement for a DSMB to review interim safety data at defined intervals throughout the study -Revised procedures for reporting AESIs; specified that specific DG manifestations will be captured in the DGSSS and not in the eCRF as a complication of the disease, as originally specified -Provided AESIs that have been identified for relamorelin.