E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo in glycated hemoglobin (HbA1c) change in participants with T2DM (Type 2 Diabetes Mellitus) inadequately controlled with diet and exercise. |
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E.2.2 | Secondary objectives of the trial |
-To compare the effects of once weekly injection of efpeglenatide with placebo on glycemic control.
-To compare the effects of once weekly injection of efpeglenatide with placebo on body weight. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Participants must be at least 18 years of age at the time of signing the informed consent.
-Participants with T2DM, based on the World Health Organization (WHO) diagnosis guideline and treated with diet and exercise.
-Hemoglobin A1c between 7.0% and 10.0% (inclusive) measured by the central laboratory at Screening. |
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E.4 | Principal exclusion criteria |
-Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and not controlled gastroesophageal reflux disease within 6 months prior to Screening.
--History of pancreatitis (unless pancreatitis was related to gallstone and cholecystectomy has been performed) and pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, and pancreatectomy.
-Personal or family history of Medullary Thyroidian Cancer (MTC) or genetic conditions that predisposes to MTC (eg multiple endocrine neoplasia syndromes).
--Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months of screening) or planned: intravitreal injections or laser or vitrectomy surgery.
-Body weight change of ≥5 kg within the last 3 months prior to Screening.
-Systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg at Randomization
-End-stage renal disease as defined by estimated glomerular filtration rate (eGFR , by Modification of Diet in Renal Disease [MDRD]) of <15 mL/min/1.73 m2.
-Laboratory findings at the Screening Visit:
- Alanine aminotransferase (ALT ) or aspartate aminotransferase (AST ) >3 times the upper limit of the normal (ULN ) or total bilirubin >1.5 times the ULN (except in case of documented Gilbert’s syndrome).
- Amylase and/or lipase: >3 times the ULN laboratory range.
- Calcitonin ≥5.9 pmol/L (20 pg/mL).
-Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to Screening, or planned during study period.
-History of drug or alcohol abuse within 6 months prior to the time of Screening.
-Pregnant (demonstrated by serum pregnancy test at Screening) or breast-feeding women.
-Women of childbearing potential not willing to use highly effective method(s) of birth control during the study period and for at least 5 weeks after the last dose of study intervention.
-Male participant not willing to use contraception endpoints during the study period and for at least 5 weeks after the last dose of study intervention and refrain from donating sperm during this period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycated hemoglobin (HbA1c) (%): Change from Baseline to Week 30 in HbA1c (%) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1-Change in HbA1c (%): Change from Baseline to Week 56 in HbA1c (%)
2-Change in fasting plasma glucose (FPG): Change from Baseline to Week 30 and to Week 56 in FPG
3-Change in 7-point self-monitored plasma glucose (SMPG) profile: Change from Baseline to Week 30 and to Week 56 in 7-point SMPG profiles (24-hour profile, mean 24-hour SMPG, average pre breakfast SMPG, prandial glucose excursions)
4-HbA1c <7%: Percentage of patients with HbA1c <7.0% at Week 30 and Week 56
5-Rescue therapy: Number of participants Rescue therapy until Weeks 30 and 56
6-Time to rescue therapy: Time to initiation of rescue therapy
7-Change in body weight: Change from Baseline to Week 30 and to Week 56 in body weight |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-Baseline to Week 56
2-3-Baseline to Week 30, Baseline to Week 56
4-5-Week 30, Week 56
6-Week 56
7-Baseline to Week 30, Baseline to Week 56 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | 4 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Germany |
Poland |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |