Clinical trial NCT00976937: 24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-09-15
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Absolute Change From Baseline in HbA1c at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Body Weight at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Glucose Excursion at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Beta Cell Function Assessed by Homeostasis Model Assessment-Beta (HOMA-beta) at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
timeFrame: Week 24
measure: Percentage of Patients Requiring Rescue Therapy During 24-Week Period
timeFrame: Baseline up to Week 24
Other outcomes:
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
timeFrame: Week 24
measure: Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Proinsulin-to-insulin Ratio and 2-hour Postprandial Proinsulin-to-insulin Ratio at Week 24
timeFrame: Baseline, Week 24
measure: Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
timeFrame: First dose of study drug up to 3 days after the last dose administration
Locations:
city: Montgomery
country: United States
facility: Sanofi-Aventis Investigational Site Number 840019
state: Alabama
city: Muscle Shoals
country: United States
facility: Sanofi-Aventis Investigational Site Number 840003
state: Alabama
city: Mesa
country: United States
facility: Sanofi-Aventis Investigational Site Number 840022
state: Arizona
city: Anaheim
country: United States
facility: Sanofi-Aventis Investigational Site Number 840011
state: California
city: Paramount
country: United States
facility: Sanofi-Aventis Investigational Site Number 840014
state: California
city: Redlands
country: United States
facility: Sanofi-Aventis Investigational Site Number 840027
state: California
city: Augusta
country: United States
facility: Sanofi-Aventis Investigational Site Number 840021
state: Georgia
city: Roswell
country: United States
facility: Sanofi-Aventis Investigational Site Number 840007
state: Georgia
city: Chicago
country: United States
facility: Sanofi-Aventis Investigational Site Number 840016
state: Illinois
city: Chicago
country: United States
facility: Sanofi-Aventis Investigational Site Number 840018
state: Illinois
city: Evansville
country: United States
facility: Sanofi-Aventis Investigational Site Number 840001
state: Indiana
city: Baton Rouge
country: United States
facility: Sanofi-Aventis Investigational Site Number 840002
state: Louisiana
city: Clarkston
country: United States
facility: Sanofi-Aventis Investigational Site Number 840031
state: Michigan
city: Florissant
country: United States
facility: Sanofi-Aventis Investigational Site Number 840020
state: Missouri
city: Butte
country: United States
facility: Sanofi-Aventis Investigational Site Number 840006
state: Montana
city: Perrysburg
country: United States
facility: Sanofi-Aventis Investigational Site Number 840026
state: Ohio
city: Medford
country: United States
facility: Sanofi-Aventis Investigational Site Number 840004
state: Oregon
city: Altoona
country: United States
facility: Sanofi-Aventis Investigational Site Number 840025
state: Pennsylvania
city: Brentwood
country: United States
facility: Sanofi-Aventis Investigational Site Number 840009
state: Tennessee
city: Dallas
country: United States
facility: Sanofi-Aventis Investigational Site Number 840008
state: Texas
city: San Antonio
country: United States
facility: Sanofi-Aventis Investigational Site Number 840010
state: Texas
city: Adelaide
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036006
city: Box Hill
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036001
city: Elizabeth Vale
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036004
city: Geelong
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036002
city: Meadowbrook
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036005
city: Sydney
country: Australia
facility: Sanofi-Aventis Investigational Site Number 036003
city: Belem
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076005
city: Brasilia
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076001
city: Caxias Do Sul
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076006
city: Curitiba
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076003
city: Rio De Janeiro
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076002
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076004
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076007
city: Calgary
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124004
city: Hamilton
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124008
city: London
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124005
city: Montreal
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124006
city: Oakville
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124013
city: St-Romuald
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124002
city: Thornhill
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124012
city: Toronto
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124011
city: Vancouver
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124003
city: Victoria
country: Canada
facility: Sanofi-Aventis Investigational Site Number 124007
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152001
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152004
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152003
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152002
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 152005
city: Berlin
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276002
city: Ludwigshafen
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276005
city: Schkeuditz
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276004
city: Guatemala
country: Guatemala
facility: Sanofi-Aventis Investigational Site Number 320002
city: Guatemala
country: Guatemala
facility: Sanofi-Aventis Investigational Site Number 320001
city: Guatemala
country: Guatemala
facility: Sanofi-Aventis Investigational Site Number 320004
city: Guatemala
country: Guatemala
facility: Sanofi-Aventis Investigational Site Number 320005
city: Guatemala
country: Guatemala
facility: Sanofi-Aventis Investigational Site Number 320006
city: Aguascalientes
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484003
city: Chihuahua
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484010
city: Chihuahua
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484009
city: Df
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484012
city: Merida
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484008
city: México City
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484011
city: Pachuca
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484001
city: Pachuca
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484005
city: Veracruz
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484006
city: Zapopan
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 484002
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604005
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604003
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604001
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604002
city: Lima
country: Peru
facility: Sanofi-Aventis Investigational Site Number 604004
city: Bialystok
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616002
city: Bydgoszcz
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616001
city: Warszawa
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616006
city: Wroclaw
country: Poland
facility: Sanofi-Aventis Investigational Site Number 616003
city: Bacau
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642004
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642006
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642008
city: Iasi
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642010
city: Ploiesti
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642009
city: Resita
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642001
city: Suceava
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642005
city: Timisoara
country: Romania
facility: Sanofi-Aventis Investigational Site Number 642007
city: Kazan
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643002
city: St-Petersburg
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643003
city: St-Petersburg
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643005
city: St. Petersburg
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643001
city: Tyumen
country: Russian Federation
facility: Sanofi-Aventis Investigational Site Number 643004
city: Chernivtsi
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804003
city: Kiev
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804001
city: Kyiv
country: Ukraine
facility: Sanofi-Aventis Investigational Site Number 804004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: