A Randomized, Double-Blind, Placebo-Controlled, 2-arm Parallel-group, Multicenter Study With a 24-Week Treatment Period Assessing the Efficacy and Safety of AVE0010 in Patients With Type 2 Diabetes Insufficiently Controlled With Basal Insulin With or Without Sulfonylurea
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 311
- Locations
- 1
- Primary Endpoint
- Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Study Overview
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 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 19 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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 Week 24.
Intervention: Lixisenatide (AVE0010) (Drug)
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 Week 24.
Intervention: Pen auto-injector (Device)
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 Week 24.
Intervention: Sulfonylurea (Drug)
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 Week 24.
Intervention: Basal Insulin (Drug)
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 Week 24.
Intervention: Placebo (Drug)
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 Week 24.
Intervention: Pen auto-injector (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 Week 24.
Intervention: Sulfonylurea (Drug)
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 Week 24.
Intervention: Basal Insulin (Drug)
Outcomes
Primary Outcomes
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Time Frame: Baseline, Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. 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.
Secondary Outcomes
- Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24(Baseline, Week 24)
- Change From Baseline in Body Weight at Week 24(Baseline, Week 24)
- Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24(Baseline, Week 24)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24(Baseline, Week 24)
- Change From Screening in Total Insulin Dose at Week 24(Screening, Week 24)
- Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24(Week 24)
- Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24(Week 24)
- Percentage of Patients Requiring Rescue Therapy During 24-Week Period(Baseline up to Week 24)