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 version: 8.1 Level: LLT Classification code 100126
Conditions
Interventions
Product Code: AVE0010
Pharmaceutical Form: Solution for injection
CAS Number: 320367-13-3
Current Sponsor code: AVE0010
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Conc
Sponsors
Sanofi aventis US Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 blo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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.;Primary end point(s): Haemoglobin A1c | — |
Countries
Bulgaria
Outcome results
None listed