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

NCT ID: NCT00707031

Last Updated: 2016-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 639 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2010-11-30

Brief Summary

The purpose of this study is to compare the benefits and risks of lixisenatide (AVE0010) in comparison to exenatide (Byetta®), as an add-on treatment to metformin, over a period of 24 weeks of treatment, followed by an extension.

The primary objective is to assess the effects of lixisenatide in comparison to exenatide (Byetta®), as an add-on treatment to 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 (%) or HbA1c less than or equal to (<=) 6.5%, fasting plasma glucose (FPG), body weight; to evaluate safety, tolerability and to assess the impact of gastrointestinal tolerance on quality of life (QoL) (patient assessment of upper gastrointestinal disorders - quality of life [PAGI-QOL]).

Detailed Description

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

Conditions

Diabetes Mellitus, Type 2

Keywords

hyperglycemia, GLP-1, metformin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Metformin

Intervention Type: DRUG

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

Exenatide

1-step initiation regimen of exenatide: 5 mcg twice daily (BID) for 4 weeks, followed by 10 mcg BID up to the end of treatment.

Group Type: ACTIVE_COMPARATOR

Exenatide

Intervention Type: DRUG

Self administered by subcutaneous injections twice daily within the hour preceding breakfast and within the hour preceding dinner.

Prefilled pen injector

Intervention Type: DEVICE

Metformin

Intervention Type: DRUG

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

Interventions

Lixisenatide (AVE0010)

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

Intervention Type: DRUG

Pen auto-injector

Intervention Type: DEVICE

Exenatide

Self administered by subcutaneous injections twice daily within the hour preceding breakfast and within the hour preceding dinner.

Intervention Type: DRUG

Prefilled pen injector

Intervention Type: DEVICE

Metformin

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

Intervention Type: DRUG

Other Intervention Names

OptiClik®; Byetta®

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram per day for at least 3 months prior to screening visit

Exclusion Criteria

• HbA1c less than (<) 7% or greater than (>) 10% at screening
• At the time of screening age < legal age of majority
• Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
• Type 1 diabetes mellitus
• Treatment with another antidiabetic pharmacological agent than metformin within the 3 months preceding the screening
• FPG at screening >250 milligram per deciliter (mg/dL) (13.9 millimole per liter [mmol/L])
• Body mass index (BMI) less than or equal to (<=) 20 kilogram per square meter (kg/m^2)
• Weight change of >5 kg during the 3 months preceding the study
• 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 or diastolic blood pressure >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; and positive serum pregnancy test in females of childbearing potential
• Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram 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 attending 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, rimonabant, exenatide, dipeptidyl-peptidase-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
• Participation in any 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
• 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

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Sanofi-Aventis Administrative Office

Buenos Aires, , Argentina

Sanofi-Aventis Administrative Office

Vienna, , Austria

Sanofi-Aventis Administrative Office

São Paulo, , Brazil

Sanofi-Aventis Administrative Office

Bogotá, , Colombia

Sanofi-Aventis Administrative Office

Hørsholm, , Denmark

Sanofi-Aventis Administrative Office

Helsinki, , Finland

Sanofi-Aventis Administrative Office

Berlin, , Germany

Sanofi-Aventis Administrative Office

Athens, , Greece

Sanofi-Aventis Administrative Office

Budapest, , Hungary

Sanofi-Aventis Administrative Office

Milan, , Italy

Sanofi-Aventis Administrative Office

Gouda, , Netherlands

Sanofi-Aventis Administrative Office

Lysaker, , Norway

Sanofi-Aventis Administrative Office

Warsaw, , Poland

Sanofi-Aventis Administrative Office

San Juan, , Puerto Rico

Sanofi-Aventis Administrative Office

Moscow, , Russia

Sanofi-Aventis Administrative Office

Barcelona, , Spain

Sanofi-Aventis Administrative Office

Bromma, , Sweden

Countries

United States; Argentina; Austria; Brazil; Colombia; Denmark; Finland; Germany; Greece; Hungary; Italy; Netherlands; Norway; Poland; Puerto Rico; Russia; Spain; Sweden

References

Rosenstock J, Raccah D, Koranyi L, Maffei L, Boka G, Miossec P, Gerich JE. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care. 2013 Oct;36(10):2945-51. doi: 10.2337/dc12-2709. Epub 2013 May 22.

Reference Type: RESULT

PMID: 23698396 (View on PubMed)

Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

Reference Type: DERIVED

PMID: 39963952 (View on PubMed)

Other Identifiers

2007-005883-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC6019

Identifier Type: -

Identifier Source: org_study_id