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

NCT00976937 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC10780EudraCT:2008-007 334-22
• Study Type: interventional
• Target: 319
• Locations: 13 countries
• Sites: 92

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at 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.

  Week 24

Secondary Outcomes (13)

• Absolute Change From Baseline in HbA1c at Week 24

  Baseline, Week 24

• Change From Baseline in Body Weight at Week 24

  Baseline, Week 24

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

  Baseline, Week 24

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

  Baseline, Week 24

• Change From Baseline in Glucose Excursion at Week 24

  Baseline, Week 24

Other Outcomes (4)

• Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24

  Week 24

• Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24

  Baseline, Week 24

• Change From Baseline in Fasting Proinsulin-to-insulin Ratio and 2-hour Postprandial Proinsulin-to-insulin Ratio at Week 24

  Baseline, Week 24

Study Arms (2)

Lixisenatide

EXPERIMENTAL

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.

Drug: Lixisenatide (AVE0010); Device: Pen auto-injector; Drug: Sitagliptin Placebo; Drug: Metformin

Sitagliptin

ACTIVE COMPARATOR

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.

Drug: Lixisenatide Placebo; Device: Pen auto-injector; Drug: Sitagliptin; Drug: Metformin

Interventions

Lixisenatide (AVE0010) DRUG

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

Lixisenatide

Lixisenatide Placebo DRUG

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

Sitagliptin

Pen auto-injector DEVICE

Also known as: OptiClik®

Lixisenatide; Sitagliptin

Sitagliptin DRUG

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

Also known as: Januvia®

Sitagliptin

Sitagliptin Placebo DRUG

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

Lixisenatide

Metformin DRUG

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

Lixisenatide; Sitagliptin

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (92)

Sanofi-Aventis Investigational Site Number 840019

Montgomery, Alabama, 36109, United States

Location

Sanofi-Aventis Investigational Site Number 840003

Muscle Shoals, Alabama, 35661, United States

Location

Sanofi-Aventis Investigational Site Number 840022

Mesa, Arizona, 85206, United States

Location

Sanofi-Aventis Investigational Site Number 840011

Anaheim, California, 92801, United States

Location

Sanofi-Aventis Investigational Site Number 840014

Paramount, California, 90723, United States

Location

Sanofi-Aventis Investigational Site Number 840027

Redlands, California, 92374, United States

Location

Sanofi-Aventis Investigational Site Number 840021

Augusta, Georgia, 30909, United States

Location

Sanofi-Aventis Investigational Site Number 840007

Roswell, Georgia, 30076, United States

Location

Sanofi-Aventis Investigational Site Number 840016

Chicago, Illinois, 60610, United States

Location

Sanofi-Aventis Investigational Site Number 840018

Chicago, Illinois, 60616, United States

Location

Sanofi-Aventis Investigational Site Number 840001

Evansville, Indiana, 47714, United States

Location

Sanofi-Aventis Investigational Site Number 840002

Baton Rouge, Louisiana, 70808, United States

Location

Sanofi-Aventis Investigational Site Number 840031

Clarkston, Michigan, 48346, United States

Location

Sanofi-Aventis Investigational Site Number 840020

Florissant, Missouri, 63031, United States

Location

Sanofi-Aventis Investigational Site Number 840006

Butte, Montana, 59701, United States

Location

Sanofi-Aventis Investigational Site Number 840026

Perrysburg, Ohio, 43551, United States

Location

Sanofi-Aventis Investigational Site Number 840004

Medford, Oregon, 97504, United States

Location

Sanofi-Aventis Investigational Site Number 840025

Altoona, Pennsylvania, 16602, United States

Location

Sanofi-Aventis Investigational Site Number 840009

Brentwood, Tennessee, 37207, United States

Location

Sanofi-Aventis Investigational Site Number 840008

Dallas, Texas, 75230, United States

Location

Sanofi-Aventis Investigational Site Number 840010

San Antonio, Texas, 78229, United States

Location

Sanofi-Aventis Investigational Site Number 036006

Adelaide, 5000, Australia

Location

Sanofi-Aventis Investigational Site Number 036001

Box Hill, 3128, Australia

Location

Sanofi-Aventis Investigational Site Number 036004

Elizabeth Vale, 5112, Australia

Location

Sanofi-Aventis Investigational Site Number 036002

Geelong, 3220, Australia

Location

Sanofi-Aventis Investigational Site Number 036005

Meadowbrook, 4131, Australia

Location

Sanofi-Aventis Investigational Site Number 036003

Sydney, 2006, Australia

Location

Sanofi-Aventis Investigational Site Number 076005

Belém, 66073-000, Brazil

Location

Sanofi-Aventis Investigational Site Number 076001

Brasília, 71625-009, Brazil

Location

Sanofi-Aventis Investigational Site Number 076006

Caxias do Sul, 95070-560, Brazil

Location

Sanofi-Aventis Investigational Site Number 076003

Curitiba, 80060-900, Brazil

Location

Sanofi-Aventis Investigational Site Number 076002

Rio de Janeiro, 20211-340, Brazil

Location

Sanofi-Aventis Investigational Site Number 076004

São Paulo, 04024-002, Brazil

Location

Sanofi-Aventis Investigational Site Number 076007

São Paulo, 05403-000, Brazil

Location

Sanofi-Aventis Investigational Site Number 124004

Calgary, T2N 4N1, Canada

Location

Sanofi-Aventis Investigational Site Number 124008

Hamilton, L8L 5G8, Canada

Location

Sanofi-Aventis Investigational Site Number 124005

London, N6G 2M3, Canada

Location

Sanofi-Aventis Investigational Site Number 124006

Montreal, H2W 1R7, Canada

Location

Sanofi-Aventis Investigational Site Number 124013

Oakville, L6H 3P1, Canada

Location

Sanofi-Aventis Investigational Site Number 124002

Saint Romuald, G6W 5M6, Canada

Location

Sanofi-Aventis Investigational Site Number 124012

Thornhill, L4J 8L7, Canada

Location

Sanofi-Aventis Investigational Site Number 124011

Toronto, Canada

Location

Sanofi-Aventis Investigational Site Number 124003

Vancouver, V5Z 1C6, Canada

Location

Sanofi-Aventis Investigational Site Number 124007

Victoria, V8R 6V4, Canada

Location

Sanofi-Aventis Investigational Site Number 152001

Santiago, 7500347, Chile

Location

Sanofi-Aventis Investigational Site Number 152004

Santiago, 7500710, Chile

Location

Sanofi-Aventis Investigational Site Number 152003

Santiago, 8053095, Chile

Location

Sanofi-Aventis Investigational Site Number 152002

Santiago, Chile

Location

Sanofi-Aventis Investigational Site Number 152005

Santiago, Chile

Location

Sanofi-Aventis Investigational Site Number 276002

Berlin, 13125, Germany

Location

Sanofi-Aventis Investigational Site Number 276005

Ludwigshafen, 67059, Germany

Location

Sanofi-Aventis Investigational Site Number 276004

Schkeuditz, 04435, Germany

Location

Sanofi-Aventis Investigational Site Number 320002

Guatemala City, 01010, Guatemala

Location

Sanofi-Aventis Investigational Site Number 320001

Guatemala City, 01014, Guatemala

Location

Sanofi-Aventis Investigational Site Number 320004

Guatemala City, 1010, Guatemala

Location

Sanofi-Aventis Investigational Site Number 320005

Guatemala City, Guatemala

Location

Sanofi-Aventis Investigational Site Number 320006

Guatemala City, Guatemala

Location

Sanofi-Aventis Investigational Site Number 484003

Aguascalientes, 20230, Mexico

Location

Sanofi-Aventis Investigational Site Number 484010

Chihuahua City, 31000, Mexico

Location

Sanofi-Aventis Investigational Site Number 484009

Chihuahua City, 31238, Mexico

Location

Sanofi-Aventis Investigational Site Number 484012

Df, 03300, Mexico

Location

Sanofi-Aventis Investigational Site Number 484008

Mérida, 97000, Mexico

Location

Sanofi-Aventis Investigational Site Number 484011

México, 14050, Mexico

Location

Sanofi-Aventis Investigational Site Number 484001

Pachuca, 42090, Mexico

Location

Sanofi-Aventis Investigational Site Number 484005

Pachuca, 42090, Mexico

Location

Sanofi-Aventis Investigational Site Number 484006

Veracruz, 91700, Mexico

Location

Sanofi-Aventis Investigational Site Number 484002

Zapopan, 44030, Mexico

Location

Sanofi-Aventis Investigational Site Number 604005

Lima, 27, Peru

Location

Sanofi-Aventis Investigational Site Number 604003

Lima, Lima 27, Peru

Location

Sanofi-Aventis Investigational Site Number 604001

Lima, Peru

Location

Sanofi-Aventis Investigational Site Number 604002

Lima, Peru

Location

Sanofi-Aventis Investigational Site Number 604004

Lima, Peru

Location

Sanofi-Aventis Investigational Site Number 616002

Bialystok, 15-435, Poland

Location

Sanofi-Aventis Investigational Site Number 616001

Bydgoszcz, 85-822, Poland

Location

Sanofi-Aventis Investigational Site Number 616006

Warsaw, 02-507, Poland

Location

Sanofi-Aventis Investigational Site Number 616003

Wroclaw, 50-127, Poland

Location

Sanofi-Aventis Investigational Site Number 642004

Bacau, 600164, Romania

Location

Sanofi-Aventis Investigational Site Number 642006

Bucharest, 020475, Romania

Location

Sanofi-Aventis Investigational Site Number 642008

Bucharest, 022441, Romania

Location

Sanofi-Aventis Investigational Site Number 642010

Iași, 700515, Romania

Location

Sanofi-Aventis Investigational Site Number 642009

Ploieşti, 100097, Romania

Location

Sanofi-Aventis Investigational Site Number 642001

Reşiţa, 320076, Romania

Location

Sanofi-Aventis Investigational Site Number 642005

Suceava, 720262, Romania

Location

Sanofi-Aventis Investigational Site Number 642007

Timișoara, 300593, Romania

Location

Sanofi-Aventis Investigational Site Number 643002

Kazan', 420012, Russia

Location

Sanofi-Aventis Investigational Site Number 643001

Saint Petersburg, 194358, Russia

Location

Sanofi-Aventis Investigational Site Number 643003

Saint Petersburg, 195257, Russia

Location

Sanofi-Aventis Investigational Site Number 643005

Saint Petersburg, 198013, Russia

Location

Sanofi-Aventis Investigational Site Number 643004

Tyumen, 625023, Russia

Location

Sanofi-Aventis Investigational Site Number 804003

Chernivtsi, 58022, Ukraine

Location

Sanofi-Aventis Investigational Site Number 804001

Kiev, 2091, Ukraine

Location

Sanofi-Aventis Investigational Site Number 804004

Kyiv, 31156, Ukraine

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

lixisenatide; Sitagliptin Phosphate; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-us@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 15, 2009
• Study Start: August 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: October 11, 2016
• Results First Posted: October 11, 2016

Record last verified: 2016-08

Locations

US (21); ME (10); GU (5); CL (5); UA (3); AU (6); CA (10); PE (5); PL (4); RU (5); RO (8); DE (3); BR (7)