24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years
Overview[ - collapse ][ - ]
Purpose | The purpose of this study is to evaluate benefits and risks of lixisenatide (AVE0010), in comparison to sitagliptin, as an add-on treatment to metformin, in obese (body mass index [BMI] greater than or equal to 30 kilogram per square meter [kg/m^2]) type 2 diabetic patients less than 50 years of age, over a period of 24 weeks of treatment. The primary objective of this study is to assess the efficacy of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on a composite endpoint of glycemic control in terms of glycosylated hemoglobin (HbA1c) and body weight, at Week 24. Secondary objectives are to assess the effects of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on absolute changes in HbA1c values and body weight; fasting plasma glucose (FPG); plasma glucose, insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test; insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA-IR); beta cell function assessed by homeostatic model assessment of beta-cell function (HOMA-beta); to evaluate safety, tolerability, and anti-lixisenatide antibody development. |
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Condition | Type 2 Diabetes Mellitus |
Intervention | Drug: Lixisenatide (AVE0010) Drug: Lixisenatide Placebo Device: Pen auto-injector Drug: Sitagliptin Drug: Sitagliptin Placebo Drug: Metformin |
Phase | Phase 3 |
Sponsor | Sanofi |
Responsible Party | Sanofi |
ClinicalTrials.gov Identifier | NCT00976937 |
First Received | September 14, 2009 |
Last Updated | March 10, 2014 |
Last verified | March 2014 |
Tracking Information[ + expand ][ + ]
First Received Date | September 14, 2009 |
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Last Updated Date | March 10, 2014 |
Start Date | August 2009 |
Estimated Primary Completion Date | March 2011 |
Current Primary Outcome Measures | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24 [Time Frame: Week 24] [Designated as safety issue: No]Percentage of patients who met both criteria (HbA1c <7% at Week 24 and at least 5% weight loss from baseline at Week 24) is reported. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | 24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years |
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Official Title | 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 |
Brief Summary | The purpose of this study is to evaluate benefits and risks of lixisenatide (AVE0010), in comparison to sitagliptin, as an add-on treatment to metformin, in obese (body mass index [BMI] greater than or equal to 30 kilogram per square meter [kg/m^2]) type 2 diabetic patients less than 50 years of age, over a period of 24 weeks of treatment. The primary objective of this study is to assess the efficacy of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on a composite endpoint of glycemic control in terms of glycosylated hemoglobin (HbA1c) and body weight, at Week 24. Secondary objectives are to assess the effects of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on absolute changes in HbA1c values and body weight; fasting plasma glucose (FPG); plasma glucose, insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test; insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA-IR); beta cell function assessed by homeostatic model assessment of beta-cell function (HOMA-beta); to evaluate safety, tolerability, and anti-lixisenatide antibody development. |
Detailed Description | Not Provided |
Study Type | Interventional |
Study Phase | Phase 3 |
Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment |
Condition | Type 2 Diabetes Mellitus |
Intervention | Drug: Lixisenatide (AVE0010) Self-administered by subcutaneous injections once daily within the hour preceding breakfast. Drug: Lixisenatide Placebo Self-administered by subcutaneous injections once daily within the hour preceding breakfast. Device: Pen auto-injector Other Names: OptiClik®Drug: Sitagliptin Administered orally once a day in the morning with or without food at approximately the same time each day. Other Names: Januvia®Drug: Sitagliptin Placebo Administered orally once a day in the morning with or without food at approximately the same time each day. Drug: Metformin Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24. |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Completed |
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Estimated Enrollment | 319 |
Estimated Completion Date | March 2011 |
Estimated Primary Completion Date | March 2011 |
Eligibility Criteria | Inclusion criteria - Type 2 diabetes mellitus, 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 gram/day (g/day) for at least 3 months prior to the screening visit - Patients with obesity (BMI greater than equal to [>=] 30 kg/m^2) and aged from 18 years to less than 50 years Exclusion criteria - HbA1c less than (<) 7.0 percent (%) or HbA1c greater than (>) 10% at screening - Type 1 diabetes mellitus - Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method - FPG at screening >250 milligram/deciliter (mg/dL) (>13.9 millimole/ liter [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, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for example, multiple endocrine neoplasia syndromes) - 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, electrocardiogram (ECG) or vital signs at the time of screening that in the judgment of the investigator or any sub-investigator could have precludes 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 millimeter of mercury (mmHg) or >110 mmHg, respectively - Laboratory findings at the time of screening : Amylase and/or lipase >3 times the upper limit of normal (ULN) laboratory range; alanine aminotransferase (ALT): >3 times ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb), positive serum pregnancy test in females of childbearing potential, and calcitonin >=20 picogram per milliliter (pg/mL) (5.9 picomole per liter) - Patients who are considered by the investigator or any sub-investigator as inappropriate for the study for any reason (for example, 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) - Use of other oral or injectable antidiabetic or hypoglycemic agents than metformin (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, exenatide, dipeptidyl peptidase IV (DPP-IV) inhibitors, insulin) within 3 months prior to the time of screening - History of bariatric surgery, anti-obesity treatment, or unstable diet 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, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening - Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide) - Allergic reaction to any glucagon like peptide-1 (GLP 1) agonist in the past (for example, exenatide, liraglutide) or to metacresol - History of a serious hypersensitivity reaction to sitagliptin - Moderate or severe renal impairment (creatinine clearance inferior to 50 milliliter/minute [mL/min]) - Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in period (>2 injections missed or >2 capsules missed); and patient with any adverse event which could have precludes the inclusion in the study, as assessed by the investigator |
Gender | Both |
Ages | 18 Years |
Accepts Healthy Volunteers | No |
Contacts | Not Provided |
Location Countries | United States, Australia, Brazil, Canada, Chile, Germany, Guatemala, Mexico, Peru, Poland, Romania, Russian Federation, Ukraine |
Administrative Information[ + expand ][ + ]
NCT Number | NCT00976937 |
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Other Study ID Numbers | EFC10780 |
Has Data Monitoring Committee | Yes |
Information Provided By | Sanofi |
Study Sponsor | Sanofi |
Collaborators | Not Provided |
Investigators | Study Director: Clinical Sciences & Operations Sanofi |
Verification Date | March 2014 |
Locations[ + expand ][ + ]
Sanofi-Aventis Investigational Site Number 840019 | Montgomery, Alabama, United States, 36109 |
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Sanofi-Aventis Investigational Site Number 840003 | Muscle Shoals, Alabama, United States, 35661 |
Sanofi-Aventis Investigational Site Number 840022 | Mesa, Arizona, United States, 85206 |
Sanofi-Aventis Investigational Site Number 840011 | Anaheim, California, United States, 92801 |
Sanofi-Aventis Investigational Site Number 840014 | Paramount, California, United States, 90723 |
Sanofi-Aventis Investigational Site Number 840027 | Redlands, California, United States, 92374 |
Sanofi-Aventis Investigational Site Number 840021 | Augusta, Georgia, United States, 30909 |
Sanofi-Aventis Investigational Site Number 840007 | Roswell, Georgia, United States, 30076 |
Sanofi-Aventis Investigational Site Number 840018 | Chicago, Illinois, United States, 60616 |
Sanofi-Aventis Investigational Site Number 840016 | Chicago, Illinois, United States, 60610 |
Sanofi-Aventis Investigational Site Number 840001 | Evansville, Indiana, United States, 47714 |
Sanofi-Aventis Investigational Site Number 840002 | Baton Rouge, Louisiana, United States, 70808 |
Sanofi-Aventis Investigational Site Number 840031 | Clarkston, Michigan, United States, 48346 |
Sanofi-Aventis Investigational Site Number 840020 | Florissant, Missouri, United States, 63031 |
Sanofi-Aventis Investigational Site Number 840006 | Butte, Montana, United States, 59701 |
Sanofi-Aventis Investigational Site Number 840026 | Perrysburg, Ohio, United States, 43551 |
Sanofi-Aventis Investigational Site Number 840004 | Medford, Oregon, United States, 97504 |
Sanofi-Aventis Investigational Site Number 840025 | Altoona, Pennsylvania, United States, 16602 |
Sanofi-Aventis Investigational Site Number 840009 | Brentwood, Tennessee, United States, 37207 |
Sanofi-Aventis Investigational Site Number 840008 | Dallas, Texas, United States, 75230 |
Sanofi-Aventis Investigational Site Number 840010 | San Antonio, Texas, United States, 78229 |
Sanofi-Aventis Investigational Site Number 036006 | Adelaide, Australia, 5000 |
Sanofi-Aventis Investigational Site Number 036001 | Box Hill, Australia, 3128 |
Sanofi-Aventis Investigational Site Number 036004 | Elizabeth Vale, Australia, 5112 |
Sanofi-Aventis Investigational Site Number 036002 | Geelong, Australia, 3220 |
Sanofi-Aventis Investigational Site Number 036005 | Meadowbrook, Australia, 4131 |
Sanofi-Aventis Investigational Site Number 036003 | Sydney, Australia, 2006 |
Sanofi-Aventis Investigational Site Number 076005 | Belem, Brazil, 66073-000 |
Sanofi-Aventis Investigational Site Number 076001 | Brasilia, Brazil, 71625-009 |
Sanofi-Aventis Investigational Site Number 076006 | Caxias Do Sul, Brazil, 95070-560 |
Sanofi-Aventis Investigational Site Number 076003 | Curitiba, Brazil, 80060-900 |
Sanofi-Aventis Investigational Site Number 076002 | Rio De Janeiro, Brazil, 20211-340 |
Sanofi-Aventis Investigational Site Number 076007 | Sao Paulo, Brazil, 05403-000 |
Sanofi-Aventis Investigational Site Number 076004 | Sao Paulo, Brazil, 04024-002 |
Sanofi-Aventis Investigational Site Number 124004 | Calgary, Canada, T2N 4N1 |
Sanofi-Aventis Investigational Site Number 124008 | Hamilton, Canada, L8L 5G8 |
Sanofi-Aventis Investigational Site Number 124005 | London, Canada, N6G 2M3 |
Sanofi-Aventis Investigational Site Number 124006 | Montreal, Canada, H2W 1R7 |
Sanofi-Aventis Investigational Site Number 124013 | Oakville, Canada, L6H 3P1 |
Sanofi-Aventis Investigational Site Number 124002 | St-Romuald, Canada, G6W 5M6 |
Sanofi-Aventis Investigational Site Number 124012 | Thornhill, Canada, L4J 8L7 |
Sanofi-Aventis Investigational Site Number 124011 | Toronto, Canada |
Sanofi-Aventis Investigational Site Number 124003 | Vancouver, Canada, V5Z 1C6 |
Sanofi-Aventis Investigational Site Number 124007 | Victoria, Canada, V8R 6V4 |
Sanofi-Aventis Investigational Site Number 152005 | Santiago, Chile |
Sanofi-Aventis Investigational Site Number 152002 | Santiago, Chile |
Sanofi-Aventis Investigational Site Number 152003 | Santiago, Chile, 8053095 |
Sanofi-Aventis Investigational Site Number 152004 | Santiago, Chile, 7500710 |
Sanofi-Aventis Investigational Site Number 152001 | Santiago, Chile, 7500347 |
Sanofi-Aventis Investigational Site Number 276002 | Berlin, Germany, 13125 |
Sanofi-Aventis Investigational Site Number 276005 | Ludwigshafen, Germany, 67059 |
Sanofi-Aventis Investigational Site Number 276004 | Schkeuditz, Germany, 04435 |
Sanofi-Aventis Investigational Site Number 320001 | Guatemala, Guatemala, 01014 |
Sanofi-Aventis Investigational Site Number 320002 | Guatemala, Guatemala, 01010 |
Sanofi-Aventis Investigational Site Number 320004 | Guatemala, Guatemala, 1010 |
Sanofi-Aventis Investigational Site Number 320005 | Guatemala, Guatemala |
Sanofi-Aventis Investigational Site Number 320006 | Guatemala, Guatemala |
Sanofi-Aventis Investigational Site Number 484003 | Aguascalientes, Mexico, 20230 |
Sanofi-Aventis Investigational Site Number 484010 | Chihuahua, Mexico, 31000 |
Sanofi-Aventis Investigational Site Number 484009 | Chihuahua, Mexico, 31238 |
Sanofi-Aventis Investigational Site Number 484012 | Df, Mexico, 03300 |
Sanofi-Aventis Investigational Site Number 484008 | Merida, Mexico, 97000 |
Sanofi-Aventis Investigational Site Number 484011 | México City, Mexico, 14050 |
Sanofi-Aventis Investigational Site Number 484005 | Pachuca, Mexico, 42090 |
Sanofi-Aventis Investigational Site Number 484001 | Pachuca, Mexico, 42090 |
Sanofi-Aventis Investigational Site Number 484006 | Veracruz, Mexico, 91700 |
Sanofi-Aventis Investigational Site Number 484002 | Zapopan, Mexico, 44030 |
Sanofi-Aventis Investigational Site Number 604002 | Lima, Peru |
Sanofi-Aventis Investigational Site Number 604003 | Lima, Peru, Lima 27 |
Sanofi-Aventis Investigational Site Number 604001 | Lima, Peru |
Sanofi-Aventis Investigational Site Number 604005 | Lima, Peru, 27 |
Sanofi-Aventis Investigational Site Number 604004 | Lima, Peru |
Sanofi-Aventis Investigational Site Number 616002 | Bialystok, Poland, 15-435 |
Sanofi-Aventis Investigational Site Number 616001 | Bydgoszcz, Poland, 85-822 |
Sanofi-Aventis Investigational Site Number 616006 | Warszawa, Poland, 02-507 |
Sanofi-Aventis Investigational Site Number 616003 | Wroclaw, Poland, 50-127 |
Sanofi-Aventis Investigational Site Number 642004 | Bacau, Romania, 600164 |
Sanofi-Aventis Investigational Site Number 642006 | Bucuresti, Romania, 020475 |
Sanofi-Aventis Investigational Site Number 642008 | Bucuresti, Romania, 022441 |
Sanofi-Aventis Investigational Site Number 642010 | Iasi, Romania, 700515 |
Sanofi-Aventis Investigational Site Number 642009 | Ploiesti, Romania, 100097 |
Sanofi-Aventis Investigational Site Number 642001 | Resita, Romania, 320076 |
Sanofi-Aventis Investigational Site Number 642005 | Suceava, Romania, 720262 |
Sanofi-Aventis Investigational Site Number 642007 | Timisoara, Romania, 300593 |
Sanofi-Aventis Investigational Site Number 643002 | Kazan, Russian Federation, 420012 |
Sanofi-Aventis Investigational Site Number 643003 | St-Petersburg, Russian Federation, 195257 |
Sanofi-Aventis Investigational Site Number 643005 | St-Petersburg, Russian Federation, 198013 |
Sanofi-Aventis Investigational Site Number 643001 | St. Petersburg, Russian Federation, 194358 |
Sanofi-Aventis Investigational Site Number 643004 | Tyumen, Russian Federation, 625023 |
Sanofi-Aventis Investigational Site Number 804003 | Chernivtsi, Ukraine, 58022 |
Sanofi-Aventis Investigational Site Number 804001 | Kiev, Ukraine, 2091 |
Sanofi-Aventis Investigational Site Number 804004 | Kyiv, Ukraine, 31156 |