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

NCT ID: NCT00715624

Last Updated: 2016-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 496 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2011-02-28

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 basal insulin 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 basal insulin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction at Week 24.

The secondary objectives are to assess the effects of lixisenatide when added to basal insulin on body weight, 2-hour postprandial plasma glucose (PPG) after standardized meal challenge test, percentage of patients reaching HbA1c less than 7 percent (%), percentage of patients reaching HbA1c less than or equal to 6.5%, fasting plasma glucose (FPG), change in 7-point self-monitored plasma glucose (SMPG) profiles, change in basal insulin and total insulin doses; to evaluate safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.

Detailed Description

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 patients.

Conditions

Diabetes Mellitus, Type 2

Keywords

hyperglycemia, GLP-1, metformin, insulin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

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.

Basal Insulin

Intervention Type: DRUG

Dose to be kept stable.

Metformin

Intervention Type: DRUG

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

Pen auto-injector

Intervention Type: DEVICE

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.

Basal Insulin

Intervention Type: DRUG

Dose to be kept stable.

Metformin

Intervention Type: DRUG

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

Pen auto-injector

Intervention Type: DEVICE

Interventions

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

Basal Insulin

Dose to be kept stable.

Intervention Type: DRUG

Metformin

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

Intervention Type: DRUG

Pen auto-injector

Intervention Type: DEVICE

Other Intervention Names

OptiClik®

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with basal insulin with or without metformin

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 basal insulin for less than 3 months prior to screening or insulin regimen changed during the last 3 months prior to screening
• Basal insulin dose at screening <30 units/day and/or not at a stable dose (+/- 20 percent [%]) during the last 2 months
• If treatment with metformin, no stable dose of at least 1.5 gram/day (except for South Korea: at least 1.0 gram/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])
• 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, or 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 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 other than metformin or basal insulin (for example, sulfonylurea, alpha-glucosidase inhibitor, thiazolidinedione, rimonabant, exenatide, dipeptidyl-peptidase-4 inhibitors, fast-acting insulin for 1 week or more) 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
• Any previous treatment with lixisenatide or participation in any previous study with lixisenatide
• Use of any investigational drug within 3 months prior to study
• Renal impairment defined with creatinine >1.4 mg/dL in women and creatinine >1.5 mg/dL in men (applicable only for patients with metformin treatment)
• End-stage renal disease as defined by a calculated serum creatinine clearance of <15 milliliter/minute 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 the previous 6 months
• History of 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

São Paulo, , Brazil

Sanofi-Aventis Administrative Office

Laval, , Canada

Sanofi-Aventis Administrative Office

Santiago, , Chile

Sanofi-Aventis Administrative Office

Cairo, , Egypt

Sanofi-Aventis Administrative Office

Paris, , France

Sanofi-Aventis Administrative Office

Berlin, , Germany

Sanofi-Aventis Administrative Office

Mumbai, , India

Sanofi-Aventis Administrative Office

Milan, , Italy

Sanofi-Aventis Administrative Office

México, , Mexico

Sanofi-Aventis Administrative Office

San Juan, , Puerto Rico

Sanofi-Aventis Administrative Office

Moscow, , Russia

Sanofi-Aventis Administrative Office

Seoul, , South Korea

Sanofi-Aventis Administrative Office

Istanbul, , Turkey (Türkiye)

Sanofi-Aventis Administrative Office

Guildford Surrey, , United Kingdom

Countries

United States; Brazil; Canada; Chile; Egypt; France; Germany; India; Italy; Mexico; Puerto Rico; Russia; South Korea; Turkey (Türkiye); United Kingdom

References

Riddle MC, Aronson R, Home P, Marre M, Niemoeller E, Miossec P, Ping L, Ye J, Rosenstock J. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care. 2013 Sep;36(9):2489-96. doi: 10.2337/dc12-2454. Epub 2013 Apr 29.

Reference Type: RESULT

PMID: 23628617 (View on PubMed)

Yao J, Zhang M, Zhang X, Zhang J. Impact of Type 2 Diabetes Duration on the Efficacy and Safety of Add-on Lixisenatide in Asian Individuals Receiving Basal Insulin: A Pooled Analysis. Diabetes Ther. 2023 Apr;14(4):653-669. doi: 10.1007/s13300-023-01369-6. Epub 2023 Feb 21.

Reference Type: DERIVED

PMID: 36809495 (View on PubMed)

Davidson JA, Stager W, Paranjape S, Berria R, Leiter LA. Achieving postprandial glucose control with lixisenatide improves glycemic control in patients with type 2 diabetes on basal insulin: a post-hoc analysis of pooled data. Clin Diabetes Endocrinol. 2020 Jan 14;6:2. doi: 10.1186/s40842-019-0088-5. eCollection 2020.

Reference Type: DERIVED

PMID: 31956422 (View on PubMed)

Charbonnel B, Bertolini M, Tinahones FJ, Domingo MP, Davies M. Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta-analysis. J Diabetes Complications. 2014 Nov-Dec;28(6):880-6. doi: 10.1016/j.jdiacomp.2014.07.007. Epub 2014 Jul 18.

Reference Type: DERIVED

PMID: 25130920 (View on PubMed)

Other Identifiers

2007-005886-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC6016

Identifier Type: -

Identifier Source: org_study_id