GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Pioglitazone

NCT00763815 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC6017EudraCT: 2007-005884-92
• Study Type: interventional
• Target: 484
• Locations: 13 countries
• Sites: 150

Brief Summary

The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to pioglitazone with or without metformin, over a period of 24 weeks of treatment, followed by an extension. The primary objective is to assess the effects of lixisenatide when added to pioglitazone on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24. Secondary objectives are to assess the effects of lixisenatide when added to pioglitazone on the percentage of patients reaching HbA1c less than 7 percent (%) and less than or equal to 6.5%, fasting plasma glucose (FPG), body weight, beta-cell function (assessed by homeostatic model assessment of beta-cell function \[HOMA-beta\]), and on fasting plasma insulin (FPI), to assess the safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.

Conditions

Diabetes Mellitus Type 2

Keywords

hyperglycemia GLP-1 pioglitazone

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24

  Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

  Baseline, Week 24

Secondary Outcomes (7)

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

  Baseline, Week 24

• Change From Baseline in Body Weight at Week 24

  Baseline, Week 24

• Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24

  Baseline, Week 24

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

  Week 24

• Percentage of Patients With HbA1c Level Less Than or Equal to 6.5% at Week 24

  Week 24

Other Outcomes (2)

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

  Baseline, Week 24

• Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia

  First dose of study drug up to 3 days after the last dose administration, for up to 132 weeks

Study Arms (2)

Lixisenatide

EXPERIMENTAL

2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.

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

Placebo

PLACEBO COMPARATOR

2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.

Drug: Placebo; Device: Pen auto-injector; Drug: Pioglitazone; Drug: Metformin

Interventions

Lixisenatide (AVE0010) DRUG

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

Lixisenatide

Placebo DRUG

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

Placebo

Pen auto-injector DEVICE

Also known as: OptiClik®

Lixisenatide; Placebo

Pioglitazone DRUG

Dose to be kept stable.

Lixisenatide; Placebo

Metformin DRUG

Metformin, if given to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.

Lixisenatide; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with pioglitazone

You may not qualify if:

• HbA1c less than (\<) 7 percent (%) or greater than (\>) 10% at screening
• At the time of screening age \<legal age of majority
• Pregnant or breastfeeding women and women of childbearing potential without effective contraceptive method of birth control
• Type 1 diabetes mellitus
• Pioglitazone not at a stable dose of at least 30 milligram per day (mg/day) for at least 3 months prior to screening
• If treatment with metformin, no stable dose of at least 1.5 gram per day (g/day) for at least 3 months prior to screening visit
• FPG at screening \>250 milligram per deciliter (mg/dL) (\>13.9 millimole per liter \[mmol/L\])
• Body mass index less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2)
• 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, or inflammatory bowel disease
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
• Hemoglobinopathy or hemolytic anemia, or receipt of blood or plasma products within3 months prior to the time of screening
• History of myocardial infarction or stroke within the last 6 months prior to screening
• Known history of drug or alcohol abuse within 6 months prior to the time of screening
• Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period

Sponsors & Collaborators

• Sanofi: lead

Study Sites (150)

Sanofi-Aventis Investigational Site Number 840723

Birmingham, Alabama, 35205, United States

Location

Sanofi-Aventis Investigational Site Number 840744

Birmingham, Alabama, 35205, United States

Location

Sanofi-Aventis Investigational Site Number 840867

Birmingham, Alabama, 35235, United States

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Sanofi-Aventis Investigational Site Number 840720

Birmingham, Alabama, 35242, United States

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Sanofi-Aventis Investigational Site Number 840855

Mobile, Alabama, 36608, United States

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Sanofi-Aventis Investigational Site Number 840863

Mobile, Alabama, 36608, United States

Location

Sanofi-Aventis Investigational Site Number 840775

Chandler, Arizona, 85224, United States

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Sanofi-Aventis Investigational Site Number 840722

Mesa, Arizona, 85213, United States

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Sanofi-Aventis Investigational Site Number 840769

Phoenix, Arizona, 85050, United States

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Sanofi-Aventis Investigational Site Number 840729

Harrisburg, Arkansas, 72432, United States

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Sanofi-Aventis Investigational Site Number 840776

Mountain Home, Arkansas, 72653, United States

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Sanofi-Aventis Investigational Site Number 840795

Artesia, California, 90701, United States

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Sanofi-Aventis Investigational Site Number 840782

Chino, California, 91710, United States

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Sanofi-Aventis Investigational Site Number 840785

Huntington Beach, California, 92648, United States

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Sanofi-Aventis Investigational Site Number 840858

La Jolla, California, 92037, United States

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Sanofi-Aventis Investigational Site Number 840784

Los Banos, California, 93635, United States

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Sanofi-Aventis Investigational Site Number 840773

Mission Hills, California, 91345, United States

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Sanofi-Aventis Investigational Site Number 840707

Mission Viejo, California, 92691, United States

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Sanofi-Aventis Investigational Site Number 840733

Northridge, California, 91325, United States

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Sanofi-Aventis Investigational Site Number 840864

Roseville, California, 95661, United States

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Sanofi-Aventis Investigational Site Number 840772

San Diego, California, 92123, United States

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Sanofi-Aventis Investigational Site Number 840743

San Mateo, California, 94401, United States

Location

Sanofi-Aventis Investigational Site Number 840721

Stockton, California, 95204, United States

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Sanofi-Aventis Investigational Site Number 840763

West Hills, California, 91307, United States

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Sanofi-Aventis Investigational Site Number 840872

Colorado Springs, Colorado, 80907, United States

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Sanofi-Aventis Investigational Site Number 840868

Colorado Springs, Colorado, 80909, United States

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Sanofi-Aventis Investigational Site Number 840727

Jacksonville, Florida, 32216, United States

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Sanofi-Aventis Investigational Site Number 840745

New Port Richey, Florida, 34652, United States

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Sanofi-Aventis Investigational Site Number 840761

Oviedo, Florida, 32765, United States

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Sanofi-Aventis Investigational Site Number 840799

Wellington, Florida, 33414, United States

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Sanofi-Aventis Investigational Site Number 840857

Augusta, Georgia, 30909, United States

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Sanofi-Aventis Investigational Site Number 840724

Idaho Falls, Idaho, 83404, United States

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Sanofi-Aventis Investigational Site Number 840791

Chicago, Illinois, 60611, United States

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Sanofi-Aventis Investigational Site Number 840738

Avon, Indiana, 46123, United States

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Sanofi-Aventis Investigational Site Number 840794

Indianapolis, Indiana, 46260, United States

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Sanofi-Aventis Investigational Site Number 840767

Kansas City, Kansas, 66160-7321, United States

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Sanofi-Aventis Investigational Site Number 840779

Lansing, Kansas, 66043, United States

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Sanofi-Aventis Investigational Site Number 840739

Wichita, Kansas, 67203, United States

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Sanofi-Aventis Investigational Site Number 840789

Lexington, Kentucky, 40503, United States

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Sanofi-Aventis Investigational Site Number 840850

Lexington, Kentucky, 40504, United States

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Sanofi-Aventis Investigational Site Number 840862

Baton Rouge, Louisiana, 70808, United States

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Sanofi-Aventis Investigational Site Number 840879

Shreveport, Louisiana, 71101, United States

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Sanofi-Aventis Investigational Site Number 840764

Hyattsville, Maryland, 20783, United States

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Sanofi-Aventis Investigational Site Number 840871

Rockville, Maryland, 20850, United States

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Sanofi-Aventis Investigational Site Number 840851

Russells Mills, Massachusetts, 2747, United States

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Sanofi-Aventis Investigational Site Number 840708

Kalamazoo, Michigan, 49001, United States

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Sanofi-Aventis Investigational Site Number 840774

Bloomington, Minnesota, 55435, United States

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Sanofi-Aventis Investigational Site Number 840704

Eagan, Minnesota, 55122, United States

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Sanofi-Aventis Investigational Site Number 840717

Picayune, Mississippi, 39466, United States

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Sanofi-Aventis Investigational Site Number 840765

St Louis, Missouri, 63104, United States

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Sanofi-Aventis Investigational Site Number 840875

Las Vegas, Nevada, 89119, United States

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Sanofi-Aventis Investigational Site Number 840866

Pahrump, Nevada, 89048, United States

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Sanofi-Aventis Investigational Site Number 840865

New York, New York, 10010, United States

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Sanofi-Aventis Investigational Site Number 840766

New York, New York, 10021, United States

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Sanofi-Aventis Investigational Site Number 840874

Staten Island, New York, 10301, United States

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Sanofi-Aventis Investigational Site Number 840762

West Seneca, New York, 14224, United States

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Sanofi-Aventis Investigational Site Number 840747

Burlington, North Carolina, 27215, United States

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Sanofi-Aventis Investigational Site Number 840760

Greensboro, North Carolina, 27401, United States

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Sanofi-Aventis Investigational Site Number 840712

High Point, North Carolina, 27262, United States

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Sanofi-Aventis Investigational Site Number 840780

Bismarck, North Dakota, 58501, United States

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Sanofi-Aventis Investigational Site Number 840877

Fargo, North Dakota, 58103, United States

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Sanofi-Aventis Investigational Site Number 840777

Athens, Ohio, 45701, United States

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Sanofi-Aventis Investigational Site Number 840741

Cleveland, Ohio, 44122, United States

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Sanofi-Aventis Investigational Site Number 840728

Dayton, Ohio, 45458, United States

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Sanofi-Aventis Investigational Site Number 840709

Mentor, Ohio, 44060, United States

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Sanofi-Aventis Investigational Site Number 840716

Norman, Oklahoma, 73069, United States

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Sanofi-Aventis Investigational Site Number 840701

Medford, Oregon, 97504, United States

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Sanofi-Aventis Investigational Site Number 840751

Beaver, Pennsylvania, 15009, United States

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Sanofi-Aventis Investigational Site Number 840798

Red Lion, Pennsylvania, 17356, United States

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Sanofi-Aventis Investigational Site Number 840792

Columbia, South Carolina, 29201, United States

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Sanofi-Aventis Investigational Site Number 840740

Simpsonville, South Carolina, 29681, United States

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Sanofi-Aventis Investigational Site Number 840726

Taylors, South Carolina, 29687-4105, United States

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Sanofi-Aventis Investigational Site Number 840711

Bristol, Tennessee, 37620, United States

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Sanofi-Aventis Investigational Site Number 840853

Colleyville, Texas, 76034, United States

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Sanofi-Aventis Investigational Site Number 840730

Houston, Texas, 77030, United States

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Sanofi-Aventis Investigational Site Number 840854

San Antonio, Texas, 78218, United States

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Sanofi-Aventis Investigational Site Number 840796

Clinton, Utah, 84015, United States

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Sanofi-Aventis Investigational Site Number 840755

Salt Lake City, Utah, 84102, United States

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Sanofi-Aventis Investigational Site Number 840756

Salt Lake City, Utah, 84107, United States

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Sanofi-Aventis Investigational Site Number 840758

Salt Lake City, Utah, 84107, United States

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Sanofi-Aventis Investigational Site Number 840753

Norfolk, Virginia, 23510, United States

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Sanofi-Aventis Investigational Site Number 840770

Norfolk, Virginia, 23510, United States

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Sanofi-Aventis Investigational Site Number 840752

Richmond, Virginia, 23220, United States

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Sanofi-Aventis Investigational Site Number 840757

Virginia Beach, Virginia, 23502, United States

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Sanofi-Aventis Investigational Site Number 840735

Spokane, Washington, 99209, United States

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Sanofi-Aventis Investigational Site Number 040706

Graz, 8036, Austria

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Sanofi-Aventis Investigational Site Number 040702

Vienna, 1030, Austria

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Sanofi-Aventis Investigational Site Number 040704

Vienna, 1060, Austria

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Sanofi-Aventis Investigational Site Number 040701

Vienna, 1100, Austria

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Sanofi-Aventis Investigational Site Number 040705

Vienna, 1100, Austria

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Sanofi-Aventis Investigational Site Number 040707

Wels, 4600, Austria

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Sanofi-Aventis Investigational Site Number 124716

Greater Sudbury, P3E 2P2, Canada

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Sanofi-Aventis Investigational Site Number 124710

London, N6A 5R8, Canada

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Sanofi-Aventis Investigational Site Number 124712

Mirabel, J7J 2K8, Canada

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Sanofi-Aventis Investigational Site Number 124705

Saint Romuald, G6W 5M6, Canada

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Sanofi-Aventis Investigational Site Number 124703

Saskatoon, S7K 3H3, Canada

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Sanofi-Aventis Investigational Site Number 124713

Scarborough, M1E 5E9, Canada

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Sanofi-Aventis Investigational Site Number 124711

Sherbrooke, J1H 5N4, Canada

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Sanofi-Aventis Investigational Site Number 124704

Smiths Falls, K7A 4W8, Canada

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Sanofi-Aventis Investigational Site Number 124701

Thornhill, L4J 8L7, Canada

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Sanofi-Aventis Investigational Site Number 124708

Vancouver, V5Z 1C6, Canada

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Sanofi-Aventis Investigational Site Number 250704

Armentières, 59427, France

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Sanofi-Aventis Investigational Site Number 250707

La Rochelle, 17019, France

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Sanofi-Aventis Investigational Site Number 250705

Labarthe-sur-Lèze, 31860, France

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Sanofi-Aventis Investigational Site Number 250702

Le Creusot, 71200, France

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Sanofi-Aventis Investigational Site Number 250701

Strasbourg, 67091, France

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Sanofi-Aventis Investigational Site Number 276708

Aßlar, 35614, Germany

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Sanofi-Aventis Investigational Site Number 276704

Berlin, 10115, Germany

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Sanofi-Aventis Investigational Site Number 276703

Künzing, 94550, Germany

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Sanofi-Aventis Investigational Site Number 276706

Leipzig, 04103, Germany

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Sanofi-Aventis Investigational Site Number 276707

Pirna, 01796, Germany

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Sanofi-Aventis Investigational Site Number 276702

Sulzbach-Rosenberg, 92237, Germany

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Sanofi-Aventis Investigational Site Number 276701

Würzburg, 97072, Germany

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Sanofi-Aventis Investigational Site Number 300705

Athens, 10552, Greece

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Sanofi-Aventis Investigational Site Number 300703

Athens, Greece

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Sanofi-Aventis Investigational Site Number 300704

Athens, Greece

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Sanofi-Aventis Investigational Site Number 300701

Thessaloniki, 56429, Greece

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Sanofi-Aventis Investigational Site Number 320702

Guatemala City, 01010, Guatemala

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Sanofi-Aventis Investigational Site Number 320701

Guatemala City, 01014, Guatemala

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Sanofi-Aventis Investigational Site Number 320703

Guatemala City, Guatemala

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Sanofi-Aventis Investigational Site Number 320704

Guatemala City, Guatemala

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Sanofi-Aventis Investigational Site Number 356701

Bangalore, 560010, India

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Sanofi-Aventis Investigational Site Number 356703

Bangalore, 560052, India

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Sanofi-Aventis Investigational Site Number 356702

Hyderabad, 500001, India

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Sanofi-Aventis Investigational Site Number 356704

Nagpur, 440012, India

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Sanofi-Aventis Investigational Site Number 484703

Mérida, 97000, Mexico

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Sanofi-Aventis Investigational Site Number 484701

Tlalnepantla, 53160, Mexico

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Sanofi-Aventis Investigational Site Number 484704

Zapopan, 44030, Mexico

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Sanofi-Aventis Investigational Site Number 604703

Lima, Lima 27, Peru

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Sanofi-Aventis Investigational Site Number 604701

Lima, LIMA 31, Peru

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Sanofi-Aventis Investigational Site Number 604702

Lima, Peru

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Sanofi-Aventis Investigational Site Number 604705

Lima, Peru

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Sanofi-Aventis Investigational Site Number 630714

Carolina, 00983, Puerto Rico

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Sanofi-Aventis Investigational Site Number 630715

Carolina, 00983, Puerto Rico

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Sanofi-Aventis Investigational Site Number 642711

Alba Iulia, 510 217, Romania

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Sanofi-Aventis Investigational Site Number 642702

Bacau, 600164, Romania

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Sanofi-Aventis Investigational Site Number 642709

Baia Mare, 430031, Romania

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Sanofi-Aventis Investigational Site Number 642701

Brasov, 500326, Romania

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Sanofi-Aventis Investigational Site Number 642712

Bucharest, 010507, Romania

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Sanofi-Aventis Investigational Site Number 642714

Bucharest, 20475, Romania

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Sanofi-Aventis Investigational Site Number 642705

Constanța, 900591, Romania

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Sanofi-Aventis Investigational Site Number 642707

Galati, 800575, Romania

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Sanofi-Aventis Investigational Site Number 642703

Ploieşti, 100097, Romania

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Sanofi-Aventis Investigational Site Number 642713

Reşiţa, 320076, Romania

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Sanofi-Aventis Investigational Site Number 642708

Satu Mare, 440055, Romania

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Sanofi-Aventis Investigational Site Number 642706

Târgu Mureş, 540061, Romania

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Sanofi-Aventis Investigational Site Number 642715

Timișoara, 300456, Romania

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Sanofi-Aventis Investigational Site Number 642710

Timișoara, 300593, Romania

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Sanofi-Aventis Investigational Site Number 792702

Erzurum, Turkey (Türkiye)

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Sanofi-Aventis Investigational Site Number 792705

Istanbul, Turkey (Türkiye)

Location

Related Publications (1)

• Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Guo H, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab. 2013 Nov;15(11):1000-7. doi: 10.1111/dom.12121. Epub 2013 May 26.

  PMID: 23627775 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

lixisenatide; Pioglitazone; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

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 30, 2008
• First Posted: October 1, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: November 28, 2016
• Results First Posted: October 11, 2016

Record last verified: 2016-10

Locations

TU (2); FR (5); DE (7); IN (4); PE (4); PR (2); RO (14); AU (6); GR (4); US (85); GU (4); ME (3); CA (10)