GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy

Diabetes Mellitus, Type 2 Clinical Trial

— GETGOAL-MONO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00688701
• Other study ID #: EFC6018
• Secondary ID: EudraCT 2007-005
• Status: Completed
• Phase: Phase 3
• First received: May 7, 2008
• Last updated: February 26, 2014
• Start date: May 2008
• Est. completion date: December 2009

Study information

• Verified date: February 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 361
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Lixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
• Placebo
Self administered by subcutaneous injections once daily within the hour preceding breakfast.

Device:
• Pen auto-injector

Locations

Country	Name	City	State
Belgium	Sanofi-Aventis Administrative Office	Diegem
India	Sanofi-Aventis Administrative Office	Mumbai
Israel	Sanofi-Aventis Administrative Office	Natanya
Japan	Sanofi-Aventis Administrative Office	Tokyo
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Mexico	Sanofi-Aventis Administrative Office	Mexico
Poland	Sanofi-Aventis Administrative Office	Warszawa
Romania	Sanofi-Aventis Administrative Office	Bucuresti
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Tunisia	Sanofi-Aventis Administrative Office	Megrine
Ukraine	Sanofi-Aventis Administrative Office	Kiev
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Belgium,  India,  Israel,  Japan,  Korea, Republic of,  Mexico,  Poland,  Romania,  Russian Federation,  Tunisia,  Ukraine, 

References & Publications (1)

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 i — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Glucose Excursion at Week 12	Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test (performed in selected sites), before study drug administration. Change was calculated by subtracting baseline value from Week 12 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.	Baseline, Week 12	No
Other	Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12	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.	Baseline, Week 12	No
Other	Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia	Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.	First dose of study drug up to 3 days after the last dose administration	Yes
Primary	Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	Absolute change = HbA1c value at Week 12 minus HbA1c value at baseline. 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 modified intent-to-treat (mITT) population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.	Baseline, Week 12	No
Secondary	Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12	The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal (performed in selected sites). Change was calculated by subtracting baseline value from Week 12 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day 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.	Baseline, Week 12	No
Secondary	Change From Baseline in Body Weight at Week 12	Change was calculated by subtracting baseline value from Week 12 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.	Baseline, Week 12	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12	Change was calculated by subtracting baseline value from Week 12 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day 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.	Baseline, Week 12	No
Secondary	Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12	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.	Week 12	No
Secondary	Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12	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.	Week 12	No
Secondary	Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period	Routine fasting self monitored plasma glucose (SMPG) and central laboratory FPG values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG was performed. Threshold values for fasting SMPG/FPG: from baseline to Week 8: >270 milligram/deciliter (mg/dL) (15 mmol/L) and from Week 8 to Week 12: >240 mg/dL (13.3 mmol/L). 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.	Baseline up to Week 12	No