A randomized, double-blind, double-dummy, 2-arm parallel-group, multicenter 24-week study comparing the efficacy and safety of AVE0010 to sitagliptin as add-on to metformin in obese type 2 diabetic patients younger than 50 and not adequately controlled with metformin.

• Conditions: Type II Diabetes; MedDRA version: 11.1Level: LLTClassification code 10045242Term: <Manually entered code. Term in E.1.1>

• Registration Number: EUCTR2008-007334-22-DE
• Lead Sponsor: Sanofi-Aventis Recherche & Développement

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-08-14
• Last Update Posted: 15 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 month

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: To assess the effects of AVE0010 on:<br>• Absolute changes in HbA1c values and body weight<br>• Fasting plasma glucose<br>• Plasma glucose, insulin, C peptide, glucagon and proinsulin during a 2-hour standardized meal test<br>• Insulin resistance assessed by HOMA-IR<br>• Beta cell function assessed by HOMA-beta<br><br>To assess AVE0010 safety and tolerability<br><br>To assess anti-AVE0010 antibody development;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.