E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051153 |
E.1.2 | Term | Diabetic gastroparesis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To compare the efficacy of relamorelin with that of placebo in participants with DG with respect to composite of the following core signs and symptoms of DG
o Nausea
o Abdominal pain
o Postprandial fullness
o Bloating
• To compare the safety of relamorelin with that of placebo in
participants with DG
|
|
E.2.2 | Secondary objectives of the trial |
• To assess relamorelin treatment effect on individual symptoms of DG such as nausea, abdominal pain, bloating, postprandial fullness, and vomiting
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 GI series with contrast or upper endoscopy, performed at some time before the Run-in period (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. 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:
10. Compliance with the entry of data into the hand-held electronic device on at least 10 of 14 days during the Run-in Period
11. Compliance with administration of SC twice daily injections, as evidenced by entries made by the participant using the electronic, hand-held device on at least 10 of 14 days during the Run-in Period
12. The average of the daily DGSSS from the 2-week, Run-in Period must be ≥ 12
|
|
E.4 | Principal exclusion criteria |
Both Rollover and De Novo Participants
1. Corrected QT Interval (QTc) > 470 msec in the absence of right or left bundle branch block, other intraventricular conduction delay (IVCD) with QRS duration > 120 msec, or paced beat on the ECG obtained at Screening (Visit 1)
2. Participants with a known allergy or hypersensitivity to the study treatments and their excipients (ie, mannitol or phenol)
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 at Screening (Visit -2). The sponsor may permit a participant with a positive urine drug screen (UDS) by immunoassay at Screening to continue in screening while confirmatory testing by a more specific method is carried out on an aliquot of the original urine sample. If the confirmatory test is negative, the initial positive UDS will be considered to have been a false-positive urine drug screen and the participant can continue in screening. Confirmatory testing will be done at the discretion of the sponsor and must be approved by the sponsor prior to analysis
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, may confound the study results, or may interfere significantly with the participant’s participation in the study
23. Participant is directly or indirectly involved in the conduct and administration of this study as an investigator, subinvestigator, study coordinator, other study staff member, or employee of Allergan, Inc.; or the participant is a first-degree family member, significant other, or relative residing with one of the above persons involved directly or indirectly in the study; or the participant is enrolled in this study at another clinical study site
24. Functional dyspepsia diagnosed before the diagnosis of diabetes mellitus
25. Hypersensitivity to the study treatments and their excipients (ie, mannitol or phenol)
26. Corrected QC Interval (QTc) > 470 msec in the absence of right or left bundle branch block, other intraventricular conduction delay (IVCD) with QRS duration > 120 msec, or paced beat on the ECG obtained at Screening (Visit 1) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Change from baseline to Week 12 in the weekly DGSSS
• Change from baseline to Week 52 in weekly average DGSSS
• AEs, clinical laboratory values, vital signs, ECGs, HbA1c, and antirelamorelin antibodies
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Change from baseline to Week 12 and Week 52 in the following:
o Nausea
o Abdominal pain
o Bloating
o Postprandial fullness
o Vomiting frequency |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 231 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Colombia |
Denmark |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Korea, Republic of |
Latvia |
Malaysia |
Mexico |
Philippines |
Poland |
Romania |
Russian Federation |
Saudi Arabia |
Singapore |
South Africa |
Spain |
Thailand |
Ukraine |
United Arab Emirates |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is defined as the date of the last visit of the last participant in the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |