E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 11.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 assess the efficacy of AVE0010 on a composite endpoint of glycemic control (HbA1c) and body weight in comparison to sitagliptin as an add-on treatment to metformin over a period of 24 weeks in obese type 2 diabetic patients younger than 50. |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of AVE0010 on: • Absolute changes in HbA1c values and body weight • Fasting plasma glucose • Plasma glucose, insulin, C peptide, glucagon and proinsulin during a 2-hour standardized meal test • Insulin resistance assessed by HOMA-IR • Beta cell function assessed by HOMA-beta
To assess AVE0010 safety and tolerability
To assess anti-AVE0010 antibody development |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with type 2 diabetes mellitus, as defined by WHO, diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 g/day for at least 3 months prior to the screening visit. 2. Patients with obesity (BMI ≥ 30kg/m2) and aged from 18 years to less than 50 years. 3. Written informed consent obtained |
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E.4 | Principal exclusion criteria |
Exclusion criteria related to study methodology: 1. HbA1c < 7.0% or HbA1c >10% at screening 2. Type 1 diabetes mellitus 3. Pregnancy or lactation 4. Women of childbearing potential with no effective contraceptive method. Women of childbearing potential (pre-menopausal, not surgically sterile women for at least 3 months prior to the time of screening) must have a confirmed negative serum pregnancy test at screening visit. 5. Fasting Plasma Glucose at screening > 250 mg/dL (> 13.9 mmol/L) 6. Weight change of more than 5 kg during the 3 months preceding the screening visit 7. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g multiple endocrine neoplasia syndromes), 8. History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening 9. Hemoglobinopathy or hemolytic anemia or receipt of blood or plasma products within 3 months prior to the time of screening 10. Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization 11. Known history of drug or alcohol abuse within 6 months prior to the time of screening 12. Any clinically significant abnormality identified on physical examination, laboratory tests, ECG or vital signs at the time of screening that in the judgment of the investigator or any sub investigator would preclude safe completion of the study or constrains efficacy assessment such as major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require laser treatment within the study period. 13. Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure > 180 mmHg or > 110 mmHg, respectively 14. Laboratory findings at the time of screening: − Amylase and/or lipase > 3 times the upper limit of the normal laboratory range − ALT > 3 ULN − Total bilirubin: > 1.5 times the upper limit of the normal laboratory range (except in case of Gilbert’s syndrome) − Hemoglobin < 11 g/dL and/or neutrophils < 1,500/mm3 and/or platelets < 100,000/mm3 − Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody − Positive serum pregnancy test in females of childbearing potential − Calcitonin ≥20pg/mL (5.9 pml/L) 15. Patients considered by the investigator or any sub investigator as inappropriate for this study for any reason (e.g. impossibility to meet specific protocol requirements, such as scheduled visits, being able to do self-injections, likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol, investigator or any sub investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc) 16. Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin (e.g., sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, exenatide, DPP-4 inhibitors, insulin etc.) within 3 months prior to the time of screening 17. History of bariatric surgery, anti-obesity treatment or unstable diet within 3 months prior to the time of screening. 18. Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening 19. Use of any investigational drug within 3 months prior to screening
Exclusion criteria related to AVE0010: 20. Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including(but not limited to): gastroparesis, unstable (i.e worsening) and not controlled (i.e prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening 21. Any previous treatment with AVE0010 (e.g. participation in a previous study with AVE0010) 22. Allergic reaction to any GLP 1-agonist in the past (e.g. exenatide, liraglutide) or to metacresol
Exclusion criteria related to sitagliptin: 23. History of a serious hypersensitivity reaction to sitagliptin. 24. Moderate or severe renal impairment (creatinine clearance inferior to 50 ml/min)
Additional exclusion criteria at the end of the run-in phase 25. Informed consent withdrawal (patient who is not willing to continue or fails to return) 26. Lack of compliance during the single-blind run-in period: more than 2 injections missed or more than 2 capsules missed (as reported in the patient diary) 27. Patients with any AE, which, by the judgment of the investigator would preclude the inclusion in the study A patient may not be enrolled in this study more than once (i.e. reentering the run-in phase or be randomized twice). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients with HbA1c values <7% at week 24 and a weight loss of at least 5% of baseline body weight at week 24. |
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | Information not present in EudraCT |
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 |
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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 | |
E.8.9.1 | In the Member State concerned months | 21 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 21 |