E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 | 10045242 |
|
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 efficacy of AVE2268 in reducing mean plasma glucose calculated from 10-points plasma glucose profiles after a four-week treatment period. |
|
E.2.2 | Secondary objectives of the trial |
To assess the effects of AVE2268 on fasting plasma glucose and 2-hour post prandial plasma glucose after standardized test breakfast, lunch and dinner test meals
To assess the safety and tolerabillity of AVE2268 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
see section "9.3 pharmacokinetics (selected centres only)" of the DRI6738 protocol: PK plasma and urine investigation will be done in a subgroup of patients (approximately 25% of the total, i.e. 75 patients) recruited in a subset of centres.
see section "9.4 Genotyping" of the DRI6738 protocol: genotyping of clinically relevant polymorphisms in drug-metabolizing enzymes
|
|
E.3 | Principal inclusion criteria |
·Male or female patients aged ≥ 18 years and < 75 years at screening. ·Type 2 diabetes mellitus, as defined by the American Diabetes Association, for at least one year at the time of screening (Appendix A) ·HbA1c measured at visit 1 in the range of ≥ 6.8 and ≤ 9.2 %; ·Stable metformin treatment (dose ≥ 1.5g/day for at least 3 months prior to enrollment in the study). No other antidiabetic medications are permitted for 3 months prior to enrollment ·Written informed consent/consents.
|
|
E.4 | Principal exclusion criteria |
- Modification of metformin treatment within 3 months prior to screening visit. - BMI >40kg/m2 - Administration of other investigational drugs within 60 days prior to screening visit. -Presence of any clinically significant endocrine disease (other than type 2 diabetes). Note: euthyroid patients on replacement therapy can be included if the dosage of thyroxine is stable for at least 3 months prior to screening visit - Diabetes other than type 2 diabetes - Subjects with “brittle-diabetes” or any hospitalization or emergency room visit due to poor diabetic control within the past 6 months, previous history of diabetes related dehydration leading to hospitalization, history or evidence of ketoacidosis - Presence or history of cancer within the past five years with the exception of adequately treated localized basal skin cancer or in situ uterine cervical cancer - History or presence of pancreatitis - Evidence of clinically relevant uncontrolled hypertension - Evidence within the past 6 months of myocardial infarction, stroke, retinopathy requiring laser surgery, or heart failure requiring hospitalization - Positive test for hepatitis B surface antigen and/or hepatitis C antibody - Impaired hepatic tests as shown but not limited to ALT, AST > 3 x ULN, AP > 2 x ULN and Bilirubin >1.5 x ULN If Bilirubin is >1.5 ULN, and all other liver parameters are within the limits described above, a measurement of direct and indirect Bilirubin will be done to diagnose a potential Gilbert's disease which will not be an exclusion criteria - Impaired renal function, as shown but not limited to creatinine clearance < 50 ml/min (predicted by using the Cockcroft-Gault formula) - History of proteinuria >1g/24h or presence at screening of a protein : creatinine ratio > 0.7 (g protein: g creatinine) in the absence of excessive exercise - Presence of urinary tract infection at screening - Presence of any clinically significant abnormality in blood or urinary laboratory tests performed at screening - Presence of any clinically significant abnormality on the ECG performed at the screening visit - Treatment with other antidiabetic agents (including insulin) other than metformin in the last 3 months before study entry - Prolonged use (more than 10 days) of systemic corticosteroids (or if daily dosage> 1000 μg equivalent beclomethasone) within the past 3 months or administration of systemic long-acting corticosteroids within the past 3 months or anticipated need for systemic glucocorticoids during the study -Thyroid replacement therapy if the dosage has been modified during the 3 months prior to screening visit. - Pregnant or breast-feeding women - Women of childbearing potential not protected by medically approved contraceptive method of birth control. The choice of the contraception is left to the discretion of patient's health care professional according to the age of the patient, her sexual activity and the usual medical practice of the country. Women using a hormonal method of contraception must add a second method of birth control during the course of the study. -Women of childbearing potential who are unwilling or unable to be tested for pregnancy. Pregnancy status should be checked by serum pregnancy testing prior to exposure to the investigational product and at the end of the study. - History or evidence of clinically relevant renal or urological disorder (i.e. obstructive renal disease, prostatic disorder with significant impact on miction, primary glomerular diseases...), significant hematuria (++ quantitatively assessed) - History or presence of gastrointestinal disorder, i.e. chronic diarrhea, stomach/gastric surgery, irritable bowel syndrome
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in Mean Plasma Glucose (MPG) from baseline to week 4 calculated from 10-point profiles (before, 90 and 120 min after standardized breakfast, lunch and dinner test meals and at bedtime) |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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
| |
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 | 6 |
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 | 2 |