Back to resultsGLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy (GETGOAL-MONO)
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Lixisenatide (AVE0010)
Placebo
Pen auto-injector
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring hyperglycemia, GLP-1
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
Sites / Locations
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
- Sanofi-Aventis Administrative Office
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo (Two-Step Titration)
Placebo (One-Step Titration)
Lixisenatide (Two-Step Titration)
Lixisenatide (One-Step Titration)
Arm Description
2-step initiation regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 12.
1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, then 20 mcg QD up to Week 12.
2-step initiation regimen of lixisenatide: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 12.
1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to Week 12.
Outcomes
Primary Outcome Measures
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 mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00688701
Brief Title
GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
hyperglycemia, GLP-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
361 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo (Two-Step Titration)
Arm Type
Placebo Comparator
Arm Description
2-step initiation regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 12.
Arm Title
Placebo (One-Step Titration)
Arm Type
Placebo Comparator
Arm Description
1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, then 20 mcg QD up to Week 12.
Arm Title
Lixisenatide (Two-Step Titration)
Arm Type
Experimental
Arm Description
2-step initiation regimen of lixisenatide: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 12.
Arm Title
Lixisenatide (One-Step Titration)
Arm Type
Experimental
Arm Description
1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to Week 12.
Intervention Type
Drug
Intervention Name(s)
Lixisenatide (AVE0010)
Intervention Description
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
Intervention Type
Device
Intervention Name(s)
Pen auto-injector
Other Intervention Name(s)
OptiClik®
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
Description
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 mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Body Weight at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12
Description
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.
Time Frame
Week 12
Title
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12
Description
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.
Time Frame
Week 12
Title
Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period
Description
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.
Time Frame
Baseline up to Week 12
Other Pre-specified Outcome Measures:
Title
Change From Baseline in Glucose Excursion at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12
Description
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.
Time Frame
Baseline, Week 12
Title
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
Description
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.
Time Frame
First dose of study drug up to 3 days after the last dose administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Diegem
Country
Belgium
Facility Name
Sanofi-Aventis Administrative Office
City
Mumbai
Country
India
Facility Name
Sanofi-Aventis Administrative Office
City
Natanya
Country
Israel
Facility Name
Sanofi-Aventis Administrative Office
City
Tokyo
Country
Japan
Facility Name
Sanofi-Aventis Administrative Office
City
Seoul
Country
Korea, Republic of
Facility Name
Sanofi-Aventis Administrative Office
City
Mexico
Country
Mexico
Facility Name
Sanofi-Aventis Administrative Office
City
Warszawa
Country
Poland
Facility Name
Sanofi-Aventis Administrative Office
City
Bucuresti
Country
Romania
Facility Name
Sanofi-Aventis Administrative Office
City
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis Administrative Office
City
Megrine
Country
Tunisia
Facility Name
Sanofi-Aventis Administrative Office
City
Kiev
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
22432104
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.
Results Reference
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GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy
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