GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Basal Insulin +/- Sulfonylurea (GETGOAL-L-ASIA)

Sanofi

Status and phase

Completed

Phase 3

Conditions

Diabetes Mellitus, Type 2

Treatments

Drug: Lixisenatide (AVE0010)

Device: Pen auto-injector

Drug: Placebo

Drug: Sulfonylurea

Drug: Basal Insulin

Study type

Interventional

Funder types

Industry

Identifiers

NCT00866658

EFC10887

Details and patient eligibility

About

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 sulfonylurea, over a period of 24 weeks of treatment.

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 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 daily basal insulin and total insulin doses; to evaluate safety, tolerability, pharmacokinetics (PK), and anti-lixisenatide antibody development.

Enrollment

311 patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with basal insulin with or without sulfonylurea

Exclusion criteria

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 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 <10 units/day and/or during the last 2 months dose not stable (+/- 20%)
Sulfonylurea not at a stable (unchanged) dose for at least 3 months prior to screening
FPG at screening >250 milligram/deciliter (mg/dL) (>13.9 millimole/liter [mmol/L])
History of hypoglycemia unawareness
Weight change of more than 5 kilogram (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 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 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)
Patient was an 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 sulfonylurea or basal insulin (for example, metformin, alpha glucosidase inhibitor, thiazolidinedione, rimonabant, exenatide, dipeptidyl peptidase 4 inhibitors, fast acting insulin for 1 week or more etc.) 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 screening
Participation in any previous study with lixisenatide
End-stage renal disease defined by a serum creatinine clearance of <15 milliliter/minute (mL/min) (calculated by the Cockcroft and Gault formula) and/or patients on dialysis
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
Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (>2 injections missed); and patient with any adverse event which could have precludes the inclusion in the study, as assessed by the investigator

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

311 participants in 2 patient groups, including a placebo group

Lixisenatide

Experimental group

Description:

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 Week 24.

Treatment:

Drug: Lixisenatide (AVE0010)

Device: Pen auto-injector

Drug: Basal Insulin

Drug: Sulfonylurea

Placebo

Placebo Comparator group

Description:

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 Week 24.

Treatment:

Device: Pen auto-injector

Drug: Basal Insulin