Current partner codePEPTIDESDE
NCT00976937·Phase 3·INTERVENTIONAL

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

Status

Completed

Phase

Phase 3

Enrollment

319

Locations

92

Results

Posted

Publications

0

Study summary

What the protocol is testing.

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.

Interventions

Treatment arms and agents.

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

DRUG

Sitagliptin

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

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.

Timeline

From registration to results.

  1. First posted

    Sep 15, 2009

  2. Study start

    Aug 2009

  3. Primary completion

    Mar 2011

  4. Study completion

    Mar 2011

  5. Results posted

    Oct 11, 2016

  6. Registry updated

    Oct 11, 2016

Outcomes

What the study measures.

Primary outcomes

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

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.

Secondary outcomes

Absolute Change From Baseline in HbA1c at Week 24

Time frame · Baseline, Week 24

Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. 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.

Change From Baseline in Body Weight at Week 24

Time frame · Baseline, Week 24

Change was calculated by subtracting baseline value from Week 24 value. 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.

Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24

Time frame · Baseline, Week 24

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

Time frame · Baseline, Week 24

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Change From Baseline in Glucose Excursion at Week 24

Time frame · Baseline, Week 24

Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.

Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24

Time frame · Baseline, Week 24

Change was calculated for fasting plasma insulin and 2-hour post prandial plasma insulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.

Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24

Time frame · Baseline, Week 24

Change was calculated for fasting C-peptide and 2-hour postprandial C-peptide by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24

Time frame · Baseline, Week 24

Change was calculated for fasting glucagon and 2-hour postprandial glucagon by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24

Time frame · Baseline, Week 24

Change was calculated for fasting proinsulin and 2-hour postprandial proinsulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of the study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24

Time frame · Baseline, Week 24

HOMA-IR was derived from FPG and FPI as: (FPI \[micro units per milliliter\]\*FPG \[mmol/L\]) divided by 22.5. Change was calculated for HOMA-IR by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
49 Years
Sex
ALL
Healthy volunteers
No

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

Study locations

92 registered sites.

Australia · Brazil · Canada · Chile · Germany · Guatemala · Mexico · Peru · Poland · Romania · Russia · Ukraine · United States. Showing up to 24 locations stored in the fast local snapshot.

Sanofi-Aventis Investigational Site Number 840019

Montgomery, Alabama, United States

Sanofi-Aventis Investigational Site Number 840003

Muscle Shoals, Alabama, United States

Sanofi-Aventis Investigational Site Number 840022

Mesa, Arizona, United States

Sanofi-Aventis Investigational Site Number 840011

Anaheim, California, United States

Sanofi-Aventis Investigational Site Number 840014

Paramount, California, United States

Sanofi-Aventis Investigational Site Number 840027

Redlands, California, United States

Sanofi-Aventis Investigational Site Number 840021

Augusta, Georgia, United States

Sanofi-Aventis Investigational Site Number 840007

Roswell, Georgia, United States

Sanofi-Aventis Investigational Site Number 840016

Chicago, Illinois, United States

Sanofi-Aventis Investigational Site Number 840018

Chicago, Illinois, United States

Sanofi-Aventis Investigational Site Number 840001

Evansville, Indiana, United States

Sanofi-Aventis Investigational Site Number 840002

Baton Rouge, Louisiana, United States

Sanofi-Aventis Investigational Site Number 840031

Clarkston, Michigan, United States

Sanofi-Aventis Investigational Site Number 840020

Florissant, Missouri, United States

Sanofi-Aventis Investigational Site Number 840006

Butte, Montana, United States

Sanofi-Aventis Investigational Site Number 840026

Perrysburg, Ohio, United States

Sanofi-Aventis Investigational Site Number 840004

Medford, Oregon, United States

Sanofi-Aventis Investigational Site Number 840025

Altoona, Pennsylvania, United States

Sanofi-Aventis Investigational Site Number 840009

Brentwood, Tennessee, United States

Sanofi-Aventis Investigational Site Number 840008

Dallas, Texas, United States

Sanofi-Aventis Investigational Site Number 840010

San Antonio, Texas, United States

Sanofi-Aventis Investigational Site Number 036006

Adelaide, Australia

Sanofi-Aventis Investigational Site Number 036001

Box Hill, Australia

Sanofi-Aventis Investigational Site Number 036004

Elizabeth Vale, Australia

Publications

Results and literature.

No PMID-linked publications were present in this registry snapshot.

Primary links

Continue at the source.

Related trials

More studies on Lixisenatide.

Related PeptideStat pages

Put the record in context.

Research pages describe evidence. Vendor pages, where available, describe independently tracked research-product listings and are not clinical recommendations.