24-week Study Comparing Lixisenatide (AVE0010) to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 


Tracking Information

Start Date  ICMJEAugust 2009
Estimated Primary Completion DateApril 2011   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2009)
Percentage of patients with HbA1c values <7% AND a weight loss of at least 5% of baseline body weight [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Original Primary Outcome Measures ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00976937 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE 
 (submitted: September 14, 2009)
  • Absolute change in HbA1c values [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with HbA1c values < or = 6.5% [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Absolute change in body weight [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in fasting plasma glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in plasma glucose and in ß-cell function during a test meal [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in insulin resistance assessed by HOMA-IR [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in ß-cell function assessed by HOMA-ß [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients requiring rescue therapy during the double-blind treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures ICMJESame as current

Descriptive Information

Brief Title  ICMJE24-week Study Comparing Lixisenatide (AVE0010) to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50
Official Title  ICMJEA 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
Brief Summary

The primary objective of this study is to assess the efficacy of lixisenatide (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 Objectives:

To assess the effects of AVE0010 on:

  • Absolute changes in HbA1c and body weight
  • Fasting plasma glucose
  • Plasma glucose, insulin, C peptide, glucagon and proinsulin during a 2-hour standardized meal test
  • Insulin resistance assessed by HOMA-IR
  • Beta cell function assessed by HOMA-beta
  • To assess AVE0010 safety and tolerability
  • To assess AVE0010 PK using the population PK approach and to assess anti-AVE0010 antibody development
Detailed Description

Maximum duration of 27 weeks ± 7 days (3-week screening + 24- week double-blind, double-dummy, active-controlled treatment + 3- day follow-up)

Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study
Condition  ICMJEType 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Lixisenatide (AVE0010)

    Pharmaceutical form:Injection

    Route of administration: Subcutaneous

  • Drug: Sitagliptin

    Pharmaceutical form:capsules

    Route of administration: Oral

Study Arms / Comparison Groups
  • Lixisenatide: Experimental
    Injection of lixisenatide once a day in the morning within 1 hour prior to breakfast (first 2 weeks of double-blind period: titration 10 to 15 µg, then 15 to 20 µg) and one capsule of sitagliptin placebo intake in the morning with or without food. On top of metformin background therapy
    Intervention: Drug: Lixisenatide (AVE0010)
  • Sitagliptin: Active Comparator
    One capsule of sitagliptin intake in the morning with or without food and lixisenatide matched placebo injection once a day in the morning within 1 hour prior to breakfast. On top of metformin background therapy.
    Intervention: Drug: Sitagliptin

Recruitment Information

Estimated Enrollment  ICMJE300
Estimated Completion DateApril 2011
Estimated Primary Completion DateApril 2011   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  • Patients with type 2 diabetes mellitus, as defined by WHO (21), diagnosed for at least 1 year at the time of 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.
  • Patients with obesity (BMI ≥ 30kg/m2) and aged from 18 years to less than 50 years.

Exclusion criteria

  • HbA1c < 7.0% or HbA1c >10% at screening
  • Type 1 diabetes mellitus
  • Pregnancy or lactation
  • Women of childbearing potential with no effective contraceptive method
  • Fasting Plasma Glucose at screening > 250 mg/dL (> 13.9 mmol/L)
  • Weight change of more than 5 kg during the 3 months preceding the screening visit
  • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, - inflammatory bowel disease
  • History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
  • Hemoglobinopathy or hemolytic anemia or receipt of blood or plasma products within 3 months prior to the time of screening
  • Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
  • Known history of drug or alcohol abuse within 6 months prior to the time of screening
  • 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.
  • Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure > 180 mmHg or > 110 mmHg, respectively
  • Laboratory findings at the time of screening:

    • Amylase and/or lipase > 3 times the upper limit of the normal laboratory range
    • 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
  • Use of other oral or injectable antidiabetic or hypoglycemic agents than metformin (e.g., sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, exenatide, DPP-IV inhibitors, insulin etc.) within 3 months prior to the time of screening
  • Unstable diet or unstable anti-obesity treatment within 3 months prior to the time of screening
  • Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening
  • Use of any investigational drug within 3 months prior to screening Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis and gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
  • Any previous treatment with AVE0010 (e.g. participation in a previous study with AVE0010)
  • Allergic reaction to any GLP 1-agonist in the past (e.g. exenatide, liraglutide) or to metacresol
  • History of a serious hypersensitivity reaction to sitagliptin.
  • Moderate or severe renal impairment (creatinine clearance inferior to 50 ml/mn)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

GenderBoth
Ages18 Years to 49 Years
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: For site information, send an email with site number toGV-Contact-us@sanofi-aventis.com
Location Countries  ICMJEUnited States,   Australia,   Canada,   Chile,   Mexico,   Poland,   Romania,   Russian Federation,   Ukraine

Administrative Information

NCT ID  ICMJENCT00976937
Responsible PartyInternational Clinical Development Study Director, sanofi-aventis
Study ID Numbers  ICMJEEFC10780, EudraCT:2008-007 334-22
Study Sponsor  ICMJESanofi-Aventis
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:International Clinical Development Study DirectorSanofi-Aventis
Information Provided BySanofi-Aventis