| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | The current study is designed to confirm the already observed clinically meaningful pharmacodynamic effect of AVE0010 on glycemic control, as measured by HbA1c, and to determine the clinically relevant dose range, and optimal regimen, for AVE0010 to be used in a larger scale Phase III program. It is also designed to test dose escalation of AVE0010 to 20 and 30 µg, BID and QD, to avoid or minimize the occurrence of nausea and/or vomiting. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10012613 | | E.1.2 | Term | Diabetes mellitus non-insulin-dependent | |
| 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 | | The primary objective of the study is to evaluate the dose-response relationship of AVE0010 administered once daily and twice daily with chronic dosing in metformin-treated subjects with type 2 diabetes. | |
| E.2.2 | Secondary objectives of the trial | The secondary objectives of the study are to:
•evaluate the efficacy of AVE0010 administered once daily and twice daily with chronic
dosing, based on glycemic parameters.
•evaluate the safety and tolerability of AVE0010 with chronic dosing.
•evaluate the pharmacokinetics of AVE0010 with chronic dosing. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Males or females. Female subjects must be post-menopausal (i.e., amenorrhea ≥12 consecutive months, or else follicle stimulating hormone between ≥20 and ≤128 mIU/mL and a serum estradiol level of less than 40 pg/mL) or surgically sterile for at least 3 months prior to screening.
2. Age 30 - 75 years, inclusive, at the time of screening
3. Type 2 diabetes mellitus, as defined by the American Diabetes Association, for at least one year at the time of screening [1]
4. Subjects must be treated with metformin, ≥1.0 g/day, at a stable dose (i.e., dose unchanged) for at least 3 months prior to screening.
5. Body mass index (BMI) 25 - 40 kg/m2, inclusive, at screening
6. HbA1c ≥7.0% and <9.0% at screening
7. Willingness and capability to perform specified self-injections, home blood glucose monitoring and to otherwise comply with study protocol requirements
| |
| E.4 | Principal exclusion criteria | 1. Type 1 diabetes mellitus
2. Pregnancy, lactation, or women of childbearing potential
3. Treatment with other antidiabetic agents other than metformin in the last 3 months before screening. No other antidiabetic agent is permitted during the study.
4. Outpatient use of insulin for glycemic control within the past 12 months or requiring administration of insulin at present
5. History of metabolic acidosis, including diabetic ketoacidosis
6. Use of drugs affecting insulin secretion, except beta blockers (e.g., phenytoin, diazoxide, somatostatin) within the past 6 months
7. Use of drugs affecting gastrointestinal motility (including metoclopramide, cisapride, and chronic macrolide antibiotics) within the past 6 months. Non-stimulant laxatives are permitted prior to and during the study.
8. Use of systemic glucocorticoids for one week or more within the last 3 months, or anticipated need for systemic glucocorticoids during the study
9. Clinically relevant evidence or history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to, gastroparesis, within the past 6 months
10. Previous or current history of chronic pancreatitis, stomach/gastric surgery, inflammatory bowel disease, irritable bowel syndrome or uncontrolled dyspepsia
11. Evidence of hypertension with a resting systolic or diastolic blood pressure >180 or >105 mmHg, respectively
12. Cardiovascular, hepatic, neurologic, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult (except for type 2 diabetes and associated disorders that would not affect study objectives)
13. Evidence of myocardial infarction, stroke, retinopathy requiring laser surgery, or heart failure requiring hospitalization within past 6 months
14. Presence of renal or hepatic disease at screening, i.e. serum creatinine ≥1.5 mg/dL (≥1.4 mg/dL for females), or ALT, AST, or alkaline phosphatase >2 times (total bilirubin >1.5 times) the upper limit of the normal laboratory range
15. Hemoglobinopathy or hemolytic anemia
16. Any clinically significant abnormality identified on the screening physical examination, laboratory tests, electrocardiogram (ECG) that in the judgment of the investigator would preclude safe completion of the study
17. Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
18. History of drug or alcohol abuse within the past 12 months
19. Receipt of any investigational drug or placebo within 30 days prior to screening
20. Any previous exposure to compounds in this investigational drug class, such as Exendin-4 and GLP-1 analogs
21. Blood or plasma donation of more than 500 mL during the previous 2 months before randomization and/or more than 50 mL within 2 weeks prior to screening, or receipt of blood products within 2 months prior to screening
22. Adults under guardianship and people with restricted freedom due to administrative or legal decisions
23. Subject is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
24. Mental condition rendering the subject incapable to understand the nature, scope, and possible consequences of the study
25. Visual acuity rendering the subject incapable of performing all protocol-related tasks, including self-administration of study medication and self-monitored blood glucose measurements
26. Subject unlikely to comply with the clinical study protocol; e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | |
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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.8.3 | 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.8.6 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 | |
| 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 | | Phone call 72 hours after last visit of the last patient for a post treatment follow up. | |
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
