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

NCT ID: NCT00976937

Last Updated: 2016-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 319 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2011-03-31

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lixisenatide

2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24.

Group Type: EXPERIMENTAL

Lixisenatide (AVE0010)

Intervention Type: DRUG

Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Pen auto-injector

Intervention Type: DEVICE

Sitagliptin Placebo

Intervention Type: DRUG

Administered orally once a day in the morning with or without food at approximately the same time each day.

Metformin

Intervention Type: DRUG

Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.

Sitagliptin

Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.

Group Type: ACTIVE_COMPARATOR

Lixisenatide Placebo

Intervention Type: DRUG

Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Pen auto-injector

Intervention Type: DEVICE

Sitagliptin

Intervention Type: DRUG

Administered orally once a day in the morning with or without food at approximately the same time each day.

Metformin

Intervention Type: DRUG

Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.

Interventions

Lixisenatide (AVE0010)

Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Intervention Type: DRUG

Lixisenatide Placebo

Self-administered by subcutaneous injections once daily within the hour preceding breakfast.

Intervention Type: DRUG

Pen auto-injector

Intervention Type: DEVICE

Sitagliptin

Administered orally once a day in the morning with or without food at approximately the same time each day.

Intervention Type: DRUG

Sitagliptin Placebo

Administered orally once a day in the morning with or without food at approximately the same time each day.

Intervention Type: DRUG

Metformin

Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.

Intervention Type: DRUG

Other Intervention Names

OptiClik®; Januvia®

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])

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Investigational Site Number 840019

Montgomery, Alabama, United States

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Muscle Shoals, Alabama, United States

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Mesa, Arizona, United States

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Anaheim, California, United States

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Paramount, California, United States

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Redlands, California, United States

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Augusta, Georgia, United States

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Roswell, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Evansville, Indiana, United States

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Baton Rouge, Louisiana, United States

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Clarkston, Michigan, United States

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Florissant, Missouri, United States

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Perrysburg, Ohio, United States

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Medford, Oregon, United States

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San Antonio, Texas, United States

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Adelaide, , Australia

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Geelong, , Australia

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Meadowbrook, , Australia

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Sydney, , Australia

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Belém, , Brazil

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Brasília, , Brazil

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Caxias do Sul, , Brazil

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Curitiba, , Brazil

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Rio de Janeiro, , Brazil

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Vancouver, , Canada

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Berlin, , Germany

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Ludwigshafen, , Germany

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Schkeuditz, , Germany

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Aguascalientes, , Mexico

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Chihuahua City, , Mexico

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Chihuahua City, , Mexico

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Df, , Mexico

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Mérida, , Mexico

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México, , Mexico

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Pachuca, , Mexico

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Pachuca, , Mexico

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Veracruz, , Mexico

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Zapopan, , Mexico

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

Sanofi-Aventis Investigational Site Number 616002

Bialystok, , Poland

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Bydgoszcz, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

Sanofi-Aventis Investigational Site Number 642004

Bacau, , Romania

Sanofi-Aventis Investigational Site Number 642006

Bucharest, , Romania

Sanofi-Aventis Investigational Site Number 642008

Bucharest, , Romania

Sanofi-Aventis Investigational Site Number 642010

Iași, , Romania

Sanofi-Aventis Investigational Site Number 642009

Ploieşti, , Romania

Sanofi-Aventis Investigational Site Number 642001

Reşiţa, , Romania

Sanofi-Aventis Investigational Site Number 642005

Suceava, , Romania

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Timișoara, , Romania

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Kazan', , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Tyumen, , Russia

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Chernivtsi, , Ukraine

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Kiev, , Ukraine

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Kyiv, , Ukraine

Countries

United States; Australia; Brazil; Canada; Chile; Germany; Guatemala; Mexico; Peru; Poland; Romania; Russia; Ukraine

Other Identifiers

EudraCT:2008-007 334-22

Identifier Type: -

Identifier Source: secondary_id

EFC10780

Identifier Type: -

Identifier Source: org_study_id