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 | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012613 |
E.1.2 | Term | Diabetes mellitus non-insulin-dependent |
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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 |
The primary objective of the study is to determine the effect of AVE8134 on glycemic control measured by the absolute change in A1c from baseline to endpoint |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to investigate the effects of AVE8134 on fasted plasma glucose FPG , the change of the glucose profile on select days, fasted insulin, HOMA-IR, fasted serum triglycerides, total cholesterol, HDL-C, LDL-C, VLDL, free fatty acids, hs-CRP, adiponectin, apolipoprotein and body weight, and to demonstrate the safety of AVE8134 when administered as single daily oral dose over 12 weeks. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Men or women, or 18 years of age who have confirmed type 2 diabetes mellitus as established in the medical history i.e. diagnosed before the screening visit and have either previously not been treated or are currently not on drug therapy; 2. A1c or 7. 0 and or 10. 0 at screening visit; 3. Fasted plasma glucose between 126 250 mg/dl, measured at screening visit |
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E.4 | Principal exclusion criteria |
. Diabetes other than type 2 diabetes mellitus; 2. Treatment with any anti-diabetic oral agent and/or insulin within 2 months 8 weeks prior to screening visit 1 because of potential to bias the primary evaluation ; 3. Likelihood of requiring treatment during the study period with glucose lowering drugs and/or insulin because of potential to bias the primary evaluation ; 4. Refusal or inability to give informed consents to participate in the study; 5. Inability and unwillingness to perform blood glucose monitoring using the sponsor-provided blood glucose meter at home and subject diary; 6. Positive glutamic acid decarboxylase GAD antibody prior to screening visit 1 in order to exclude LADA ; 7. Patients receiving drugs not permitted by the study protocol because of potential to bias the primary evaluation; for details see section 8.9 of the protocol - Fibrates, ezetimibe, nicotinic acid derivatives; 8. Creatine-kinase elevation of more than 2x ULN at visit 1 or two successive unexplained values above the upper limit of normal ULN . Testing must be repeated within the screening period for values between 1 and 2x ULN; 9. Impaired hepatic function, as shown by but not limited to alanine aminotransferase ALT or aspartate aminotransferase AST greater than 3x the ULN for gender/age measured at visit 1 because of the current level of knowledge of metabolism and excretion . Testing can be repeated within the screening period for values greater than 3x ULN but or 5x ULN ; 10. Impaired renal function because of the current level of knowledge of metabolism and excretion Either shown by serum creatinine above the upper limit for gender/age, or creatinine clearance 50 ml/min calculated by the Cockroft-Gault formula measured at visit 1; 11. History or presence of congestive heart failure NYHA II IV see Appendix B of the protocol ; 12. History or presence of hyperthyroidism; 13. Clinically relevant cardiovascular, hepatic, neurologic, endocrine, active cancer, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult and would, in the opinion of the investigator, preclude the safe participation of the subject in this protocol; 14. History or presence of diabetic retinopathy; 15. Patients known to have positive test for hepatitis B surface antigen and/or hepatitis C antibody, or HIV; 16. Treatment with any investigational drug or placebo in the last month 30 days before screening visit; 17. History of drug or alcohol abuse; 18. Subjects unlikely to comply with protocol, e.g. an inability and unwillingness to participate in adequate training, an uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study; 19. Subjects who have previously been treated with AVE8134; 20. Patient is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol; 21. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study; 22. Pregnancy Pregnancy status must be checked by urine pregnancy testing prior to exposure to the investigational product ; 23. Patients unable or unwilling to practice effective contraception; 24. Breast-feeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to determine the effect of AVE8134 on glycemic control measured by the absolute change in A1c from baseline to endpoint |
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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 | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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.8.5 | 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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |