Clinical trial NCT00688701: GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter 12-week Study Assessing the Efficacy and Safety of AVE0010 in Patients With Type 2 Diabetes Not Treated With Antidiabetic Agents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: hyperglycemia, GLP-1
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-06-03
Enrollment: 361
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, used in a 2-step dose titration regimen in monotherapy, over a period of 12 weeks of treatment.

The primary objective is to assess the effects of lixisenatide, in comparison to placebo, on glycemic control using a 2-step dose titration regimen in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 12.

Secondary objectives are to assess the effects of lixisenatide, in comparison to placebo, on glycemic control in terms of HbA1c reduction when it is used in a one-step dose titration regimen over a period of 12 weeks, body weight, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) after a standardized meal, to assess the safety and tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.

Detailed description: This is a double-blind, randomized, placebo-controlled, 4-arm, unbalanced design, parallel group study with a two-step titration regimen or a one-step titration regimen. The study is double-blind with regard to active and placebo treatments; however neither the study drug volume nor the titration regimens (that is, two-step or one-step) are blinded.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes mellitus, diagnosed for at least 2 months at the time of the screening visit, not treated with any antidiabetic agent

Exclusion Criteria:

* HbA1c less than (\<) 7 percent (%) or greater than (\>) 10%
* At the time of screening age \< legal age of majority
* Pregnant or breastfeeding women and women of childbearing potential without effective contraceptive method of birth control
* Type 1 diabetes mellitus
* Type 2 diabetes treated by an antidiabetic agent within the 3 months preceding the study
* Fasting plasma glucose at screening \>250 milligram per deciliter (mg/dL) (\>13.9 millimole per liter \[mmol/L\])
* Body mass index less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2)
* Weight change of more than 5 kg during the previous 3 months
* History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
* History of metabolic acidosis, including diabetic ketoacidosis within the previous year
* Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within the previous 3 months
* History of myocardial infarction, stroke, or heart failure requiring hospitalization within the previous 6 months
* Known history of drug or alcohol abuse within the previous 6 months
* 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 with a resting supine systolic 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 the upper limit of the normal (ULN) laboratory range; amylase and/or lipase: \>3 ULN; total bilirubin: \>1.5 ULN (except in case of Gilbert's syndrome); hemoglobin \<11 gram/deciliter (g/dL) and/or neutrophils \<1,500 per cubic mm (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 by physical examination, laboratory tests, electrocardiogram or vital sign at the time of screening that in the judgment of the investigator or any sub investigator precludes safe completion of the study or hinders the efficacy assessment
* Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason
* Use of systemic glucocorticoids (excluding topical application or inhaled forms) within the previous 3 months
* Participation in any previous study with lixisenatide
* Use of any investigational drug within 3 months prior to study
* End-stage renal disease as defined by a calculated serum creatinine clearance of \<15 milliliter/minute 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 the previous 6 months
* History of allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past 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: more than 2 injections missed; and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator

Primary outcomes:
measure: Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Body Weight at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12
timeFrame: Week 12
measure: Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12
timeFrame: Week 12
measure: Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period
timeFrame: Baseline up to Week 12
Other outcomes:
measure: Change From Baseline in Glucose Excursion at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12
timeFrame: Baseline, Week 12
measure: Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
timeFrame: First dose of study drug up to 3 days after the last dose administration
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Mumbai
country: India
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Tokyo
country: Japan
facility: Sanofi-Aventis Administrative Office
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis Administrative Office
city: Mexico
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Administrative Office
city: Megrine
country: Tunisia
facility: Sanofi-Aventis Administrative Office
city: Kiev
country: Ukraine
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE; EFC6018 GetGoal-Mono Study Investigators. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012 Jun;35(6):1225-31. doi: 10.2337/dc11-1935. Epub 2012 Mar 19.