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

NCT ID: NCT00713830

Last Updated: 2016-12-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

859 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2011-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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 sulfonylurea without or with 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 sulfonylurea with or without metformin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.

The secondary objectives are to assess the effects of lixisenatide on percentage of patients reaching HbA1c less than (\<) 7 percent (%); percentage of patients reaching HbA1c less than or equal to (\<=) 6.5%; body weight; fasting plasma glucose (FPG); beta-cell function assessed by homeostasis model assessment (HOMA) beta; 2-hour postprandial plasma glucose (PPG), glucagon, insulin, proinsulin, and C-peptide after a standardized meal challenge test in a sub-study in all patients in selected centers; to evaluate safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Patients who complete the 24-week main double-blind treatment would undergo a variable double-blind extension treatment, which ends for all patients at approximately the scheduled date of Week 76 visit (Visit 25) for the last randomized patient.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Mellitus, Type 2

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

hyperglycemia, GLP-1

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lixisenatide

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.

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

Sulfonylurea

Intervention Type DRUG

Sulfonylurea to be continued at maximum effective dose according to local labeling up to end of treatment.

Metformin

Intervention Type DRUG

Metformin if given to be continued at stable dose (at least 1.5 gram per day \[except at least 0.75 gram per day in Japan and 1.0 gram per day in South Korea\]) up to the end of treatment.

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Pen auto-injector

Intervention Type DEVICE

Sulfonylurea

Intervention Type DRUG

Sulfonylurea to be continued at maximum effective dose according to local labeling up to end of treatment.

Metformin

Intervention Type DRUG

Metformin if given to be continued at stable dose (at least 1.5 gram per day \[except at least 0.75 gram per day in Japan and 1.0 gram per day in South Korea\]) up to the end of treatment.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Lixisenatide (AVE0010)

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Pen auto-injector

Intervention Type DEVICE

Sulfonylurea

Sulfonylurea to be continued at maximum effective dose according to local labeling up to end of treatment.

Intervention Type DRUG

Metformin

Metformin if given to be continued at stable dose (at least 1.5 gram per day \[except at least 0.75 gram per day in Japan and 1.0 gram per day in South Korea\]) up to the end of treatment.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

OptiClik®

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with a sulfonylurea alone or a sulfonylurea in association with metformin

Exclusion Criteria

* HbA1c less than (\<) 7% or greater than (\>) 10% at screening
* At the time of screening age less than legal age of majority
* Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
* Type 1 diabetes mellitus
* Sulfonylurea less than the maximum effective dose according to local labeling
* Sulfonylurea not at a stable (unchanged) dose for at least 3 months prior to screening
* In case of treatment with metformin in association with sulfonylurea, no stable (unchanged) treatment with metformin of at least 1.5 gram per day (except at least 0.75 gram per day in Japan and at least 1.0 gram per day in South Korea), for at least 3 months prior to screening visit
* FPG at screening \>250 milligram per deciliter (mg/dL) (\>13.9 millimole per liter \[mmol/L\])
* History of hypoglycemia unawareness
* Body mass index less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2)
* Weight change of \>5 kg during the 3 months preceding the screening visit
* History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
* History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
* Hemoglobinopathy or hemolytic anemia, 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
* 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
* Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure (SBP) or diastolic blood pressure (DBP) \>180 millimeter of mercury (mmHg) or \>95 mmHg, respectively
* Laboratory findings at the time of screening: aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase: \>2 times upper limit of the normal (ULN) laboratory range; amylase and/or lipase: \>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 and/or Hepatitis C antibody
* Any clinically significant abnormality identified on physical examination, laboratory tests or vital signs at the time of screening that in the judgment of the Investigator or any sub investigator precludes safe completion of the study or constrains efficacy assessment
* Patients who are considered by the Investigator or any sub investigator as inappropriate for this 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)
* Patients with condition/concomitant diseases making them non-evaluable for the efficacy assessment
* Use of oral or injectable antidiabetic or hypoglycemic agents other than sulfonylurea and metformin (for example, alpha glucosidase inhibitor, thiazolidinedione, rimonabant, exenatide, dipeptidyl-peptidase 4 (DPP-4) inhibitors, insulin) within 3 months prior to the time of screening
* Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
* Use of any investigational drug within 3 months prior to study
* Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide)
* Renal impairment defined with serum creatinine \>1.4 mg/dL in women and serum creatinine \>1.5 mg/dL in men (applicable only for patients with metformin treatment)
* End-stage renal disease as defined by a serum creatinine clearance of \<15 milliliter/minute (calculated by the Cockcroft and Gault formula) and/or patients on dialysis (if no treatment with metformin)
* Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis and gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
* Allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past (for example, exenatide, liraglutide) or to metacresol
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Site Status

Sanofi-Aventis Administrative Office

Sofia, , Bulgaria

Site Status

Sanofi-Aventis Administrative Office

Prague, , Czechia

Site Status

Sanofi-Aventis Administrative Office

Cairo, , Egypt

Site Status

Sanofi-Aventis Administrative Office

Berlin, , Germany

Site Status

Sanofi-Aventis Administrative Office

Mumbai, , India

Site Status

Sanofi-Aventis Administrative Office

Netanya, , Israel

Site Status

Sanofi-Aventis Administrative Office

Tokyo, , Japan

Site Status

Sanofi-Aventis Administrative Office

Gouda, , Netherlands

Site Status

Sanofi-Aventis Administrative Office

Bucharest, , Romania

Site Status

Sanofi-Aventis Administrative Office

Moscow, , Russia

Site Status

Sanofi-Aventis Administrative Office

Seoul, , South Korea

Site Status

Sanofi-Aventis Administrative Office

Taipei, , Taiwan

Site Status

Sanofi-Aventis Administrative Office

Bangkok, , Thailand

Site Status

Sanofi-Aventis Administrative Office

Mégrine, , Tunisia

Site Status

Sanofi-Aventis Administrative Office

Istanbul, , Turkey (Türkiye)

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Bulgaria Czechia Egypt Germany India Israel Japan Netherlands Romania Russia South Korea Taiwan Thailand Tunisia Turkey (Türkiye)

References

Explore related publications, articles, or registry entries linked to this study.

Rosenstock J, Hanefeld M, Shamanna P, Min KW, Boka G, Miossec P, Zhou T, Muehlen-Bartmer I, Ratner RE. Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S). J Diabetes Complications. 2014 May-Jun;28(3):386-92. doi: 10.1016/j.jdiacomp.2014.01.012. Epub 2014 Jan 28.

Reference Type RESULT
PMID: 24650952 (View on PubMed)

Ahren B, Galstyan G, Gautier JF, Giorgino F, Gomez-Peralta F, Krebs M, Nikonova E, Stager W, Vargas-Uricoechea H. Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis. Diabetes Ther. 2016 Sep;7(3):583-90. doi: 10.1007/s13300-016-0179-6. Epub 2016 Jun 18.

Reference Type DERIVED
PMID: 27319011 (View on PubMed)

Yabe D, Ambos A, Cariou B, Duvnjak L, Evans M, Gonzalez-Galvez G, Lin J, Nikonova EV, de Pablos-Velasco P, Yale JF, Ahren B. Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse beta-cell function in the GetGoal-M and GetGoal-S trials. J Diabetes Complications. 2016 Sep-Oct;30(7):1385-92. doi: 10.1016/j.jdiacomp.2016.05.018. Epub 2016 May 24.

Reference Type DERIVED
PMID: 27267268 (View on PubMed)

Seino H, Onishi Y, Naito Y, Komatsu M. Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. Diabetol Metab Syndr. 2016 Jun 1;8:36. doi: 10.1186/s13098-016-0151-7. eCollection 2016.

Reference Type DERIVED
PMID: 27252787 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

EudraCT 2007-005881-11

Identifier Type: -

Identifier Source: secondary_id

EFC6015

Identifier Type: -

Identifier Source: org_study_id