GLP-1 Receptor Agonist Lixisenatide (Morning or Evening) in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin
Official Title
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin
Acronym
GETGOAL-M
Organization
SanofiINDUSTRY
Status Module
Record Verification Date
Oct 2016
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jun 2008
Primary Completion Date
Mar 2011Actual
Completion Date
Mar 2011Actual
First Submitted Date
Jul 7, 2008
First Submission Date that Met QC Criteria
Jul 7, 2008
First Posted Date
Jul 10, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 18, 2016
Results First Submitted that Met QC Criteria
Oct 24, 2016
Results First Posted Date
Dec 15, 2016Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Apr 13, 2012
Certification/Extension First Submitted that Passed QC Review
Apr 13, 2012
Certification/Extension First Posted Date
Apr 16, 2012Estimated
Last Update Submitted Date
Oct 24, 2016
Last Update Posted Date
Dec 15, 2016Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
SanofiINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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 metformin, over a period of 24 weeks of treatment, followed by an extension.
The primary objective is to assess the effects of lixisenatide as an add-on treatment to metformin in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
The secondary objectives are to assess the effect of lixisenatide, in comparison to placebo, when administered in the evening within 1 hour prior to the meal in terms of HbA1c reduction, 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), plasma glucose, plasma insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test (only in morning injection arms), body weight, beta-cell function assessed by homeostasis model assessment (HOMA)-beta, fasting plasma insulin (FPI) and adiponectin; to evaluate safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development, beta-cell function 4 weeks after study drug discontinuation (only in patients from the morning injection arms in some selected centers).
Detailed Description
Patients who complete the 24-week main double-blind treatment would undergo a variable double-blind extension treatment, which ends for all patients at approximately the scheduled date of Week 76 visit (Visit 25) for the last randomized patient.
Conditions Module
Conditions
Diabetes Mellitus, Type 2
Keywords
hyperglycemia, GLP-1, metformin
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
680Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Lixisenatide (Morning Injection)
Experimental
2-step initiation morning 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 end of treatment.
Drug: Lixisenatide (AVE0010)
Device: Pen auto-injector
Drug: Metformin
Lixisenatide (Evening Injection)
Experimental
2-step initiation evening regimen of lixisenatide: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
Drug: Lixisenatide (AVE0010)
Device: Pen auto-injector
Drug: Metformin
Placebo (Morning Injection)
Placebo Comparator
2-step initiation morning 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 end of treatment.
Drug: Placebo
Device: Pen auto-injector
Drug: Metformin
Placebo (Evening Injection)
Placebo Comparator
2-step initiation evening 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 end of treatment.
Drug: Placebo
Device: Pen auto-injector
Drug: Metformin
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Lixisenatide (AVE0010)
Drug
Self administered by subcutaneous injections once daily within the hour preceding meal (either breakfast or dinner).
Lixisenatide (Evening Injection)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
Other Outcomes
Measure
Description
Time Frame
Change From Baseline in Glucose Excursion at Week 24
Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/ day (g/day) for at least 3 months prior to screening visit
Exclusion Criteria:
HbA1c <7% 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 an antidiabetic pharmacological agent other than metformin within the 3 months preceding the screening
FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
Body mass index (BMI) <=20 kilogram per square meter (kg/m^2)
Weight change of >5 kg during the 3 months preceding the study 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 supine 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 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; positive serum pregnancy test in females of child bearing 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 or any sub-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; 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 metformin (for example, sulfonylurea, alpha glucosidase inhibitor, other thiazolidinediones, rimonabant, exenatide, dipeptidyl-peptidase-4 inhibitors, insulin) 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 study
Any previous treatment with lixisenatide or participation in a previous study with lixisenatide
Renal impairment defined with creatinine >1.4 mg/dL in women and creatinine >1.5 mg/dL in men
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 precludes the inclusion in the study, as assessed by the investigator
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Clinical Sciences & Operations
Sanofi
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Sanofi-Aventis Administrative Office
Bridgewater
New Jersey
08807
United States
sanofi-aventis Australia & New Zealand administrative office
Ahren B, Leguizamo Dimas A, Miossec P, Saubadu S, Aronson R. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M). Diabetes Care. 2013 Sep;36(9):2543-50. doi: 10.2337/dc12-2006. Epub 2013 Mar 27.
Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
A total of 1374 patients were screened of which 694 (50.5%) were screen failures; main reason for screen failure was glycosylated hemoglobin (HbA1c) values being out of the defined protocol range (greater than or equal to 7% and less than or equal to 10%). A total of 680 patients were randomized.
Recruitment Details
The study was conducted at 133 centers in 16 countries between June 30, 2008 and March 09, 2011. The overall duration of treatment was at least 76 weeks (24 weeks main double-blind treatment; variable double-blind extension treatment).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
FG001
Placebo (Evening Injection)
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Lixisenatide (Morning Injection)
Placebo
Drug
Self administered by subcutaneous injections once daily within the hour preceding meal (either breakfast or dinner).
Placebo (Evening Injection)
Placebo (Morning Injection)
Pen auto-injector
Device
Lixisenatide (Evening Injection)
Lixisenatide (Morning Injection)
Placebo (Evening Injection)
Placebo (Morning Injection)
OptiClik®
Metformin
Drug
Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
Lixisenatide (Evening Injection)
Lixisenatide (Morning Injection)
Placebo (Evening Injection)
Placebo (Morning Injection)
Baseline, Week 24
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in Body Weight at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in Fasting Proinsulin at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in 2-Hour Postprandial Proinsulin at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in Fasting C-Peptide at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in 2-Hour Postprandial C-Peptide at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in Fasting Glucagon at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in 2-Hour Postprandial Glucagon at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Baseline, Week 24
Change From Baseline in Adiponectin at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24
Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin [micro unit per milliliter]) divided by (FPG [mmol/L] minus 3.5). Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period
Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) 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 (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG >270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8.5%. 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 24
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
Baseline, Week 24
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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 24
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
Ahren B, Galstyan G, Gautier JF, Giorgino F, Gomez-Peralta F, Krebs M, Nikonova E, Stager W, Vargas-Uricoechea H. Postprandial Glucagon Reductions Correlate to Reductions in Postprandial Glucose and Glycated Hemoglobin with Lixisenatide Treatment in Type 2 Diabetes Mellitus: A Post Hoc Analysis. Diabetes Ther. 2016 Sep;7(3):583-90. doi: 10.1007/s13300-016-0179-6. Epub 2016 Jun 18.
Yabe D, Ambos A, Cariou B, Duvnjak L, Evans M, Gonzalez-Galvez G, Lin J, Nikonova EV, de Pablos-Velasco P, Yale JF, Ahren B. Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse beta-cell function in the GetGoal-M and GetGoal-S trials. J Diabetes Complications. 2016 Sep-Oct;30(7):1385-92. doi: 10.1016/j.jdiacomp.2016.05.018. Epub 2016 May 24.
2-step initiation evening regimen of volume matching placebo: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
FG002
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
FG003
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
FG00085 subjectsRandomized.
FG00185 subjects
FG002255 subjects
FG003255 subjects
Safety Population
FG00085 subjectsAll patients who were exposed to at least 1 dose, regardless of amount of treatment administered.
FG00185 subjects
FG002255 subjects
FG003255 subjects
Modified Intent-to-Treat(mITT)Population
FG00085 subjectsAll patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment.
FG00185 subjects
FG002255 subjects
FG003255 subjects
Subgroup for Standardized Meal Test
FG00085 subjectsPatients from morning injection arms where standardized meal test was performed.
FG0010 subjects
FG002255 subjects
FG0030 subjects
COMPLETED
FG00064 subjects
FG00164 subjects
FG002198 subjects
FG003185 subjects
NOT COMPLETED
FG00021 subjects
FG00121 subjects
FG00257 subjects
FG00370 subjects
Type
Comment
Reasons
Adverse Event
FG0003 subjects
FG0013 subjects
FG00221 subjects
FG00326 subjects
Lack of Efficacy
FG0002 subjects
FG0018 subjects
FG0028 subjects
FG0036 subjects
Poor Compliance to Protocol
FG0003 subjects
FG0013 subjects
FG0024 subjects
FG00316 subjects
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
Withdrawal by Subject
FG0006 subjects
FG0017 subjects
FG00215 subjects
FG00320 subjects
Familial and Personal Reasons
FG0005 subjects
FG0010 subjects
FG0025 subjects
FG0032 subjects
Investigator's Decision
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
BG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
BG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000170
BG001255
BG002255
BG003680
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00055.0± 9.4
BG00154.5± 9.2
BG00254.8± 10.4
BG003
Gender
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00089
BG001157
BG002
Race/Ethnicity, Customized
Number
participants
Title
Denominators
Categories
Race: Caucasian/White
Title
Measurements
BG000155
BG001221
BG002
Glycosylated Hemoglobin (HbA1c)
Mean
Standard Deviation
percentage of hemoglobin
Title
Denominators
Categories
Title
Measurements
BG0008.06± 0.90
BG0018.04± 0.86
BG002
Fasting Plasma Glucose (FPG)
Mean
Standard Deviation
millimole per liter (mmol/L)
Title
Denominators
Categories
Title
Measurements
BG0009.51± 2.28
BG0019.43± 2.15
BG002
2-hour Postprandial Plasma Glucose (PPG)
Number of patients analyzed = 169, 253 and 252 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
mmol/L
Title
Denominators
Categories
Title
Measurements
BG00015.51± 3.43
BG001
Body Weight
Mean
Standard Deviation
kilogram (kg)
Title
Denominators
Categories
Title
Measurements
BG00090.15± 20.14
BG00190.09± 21.10
BG002
Homeostasis Model Assessment for Beta-cell Function (HOMA-beta)
Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin [micro unit per milliliter]) divided by (fasting plasma glucose [mmol/L] minus 3.5). Number of patients analyzed = 168, 251 and 252 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
percentage of normal beta cells function
Title
Denominators
Categories
Title
Measurements
BG00041.48± 42.12
BG001
Adiponectin
Number of patients analyzed = 164, 248 and 248 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
microgram per milliliter (mcg/mL)
Title
Denominators
Categories
Title
Measurements
BG0005.61± 3.26
BG001
Fasting Plasma Insulin (FPI)
Number of patients analyzed = 168, 251 and 253 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
picomole per liter (pmol/L)
Title
Denominators
Categories
Title
Measurements
BG00075.79± 48.02
BG001
2-hour Postprandial Plasma Insulin (PPI)
Number of patients analyzed = 151, 232 and 240 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
pmol/L
Title
Denominators
Categories
Title
Measurements
BG000374.28± 266.55
BG001
Fasting C-peptide
Number of patients analyzed = 164, 252 and 249 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
nanomole per liter (nmol/L)
Title
Denominators
Categories
Title
Measurements
BG0000.90± 0.36
BG001
2-hour Postprandial C-peptide
Number of patients analyzed = 166, 251 and 249 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
nmol/L
Title
Denominators
Categories
Title
Measurements
BG0002.46± 1.08
BG001
Fasting Glucagon
Number of patients analyzed = 162, 242 and 247 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
nanogram per liter (ng/L)
Title
Denominators
Categories
Title
Measurements
BG00087.92± 29.05
BG001
2-hour Postprandial Glucagon
Number of patients analyzed = 163, 241 and 248 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
ng/L
Title
Denominators
Categories
Title
Measurements
BG000101.30± 33.88
BG001
Fasting Proinsulin
Number of patients analyzed = 142, 223 and 226 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
pmol/L
Title
Denominators
Categories
Title
Measurements
BG00031.68± 20.10
BG001
2-hour Postprandial Proinsulin
Number of patients analyzed = 139, 204 and 213 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
pmol/L
Title
Denominators
Categories
Title
Measurements
BG00083.48± 58.02
BG001
Glucose Excursion
Number of patients analyzed = 168, 252 and 252 for Placebo (Combined), Lixisenatide (Morning Injection) and Lixisenatide (Evening Injection) treatment arms, respectively.
Mean
Standard Deviation
mmol/L
Title
Denominators
Categories
Title
Measurements
BG0005.64± 2.81
BG001
Body Mass Index (BMI)
BMI was calculated by dividing body weight by the height squared.
Mean
Standard Deviation
kilogram per square meter (kg/m^2)
Title
Denominators
Categories
Title
Measurements
BG00033.12± 6.45
BG00133.22± 6.85
Duration of Diabetes
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG0005.87± 4.72
BG0016.18± 5.25
BG002
Duration of Metformin Treatment
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG0003.34± 3.45
BG0013.73± 3.34
BG002
Metformin Daily Dose
Mean
Standard Deviation
milligram (mg)
Title
Denominators
Categories
Title
Measurements
BG0002001.18± 439.70
BG0011968.82± 446.99
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population:all randomized patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment, irrespective of compliance with study protocol/procedures. Last observation carried forward used. Number of patients analyzed=patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
percentage of hemoglobin
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Units
Counts
Participants
OG000164
OG001244
OG002239
Title
Denominators
Categories
Title
Measurements
OG000-0.38± 0.075
OG001-0.87± 0.065
OG002-0.75± 0.066
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
To detect 0.5%(or 0.4%) difference between 1 lixisenatide arm and placebo(combined), 225 patients in lixisenatide arm, 170 in placebo(combined) would provide a power of 97% (or 87%) assuming common standard deviation=1.3% with 2-sided test at 5% significance. Statistical testing:2-sided at significance level=0.05. Analysis of co-variance(ANCOVA)included treatment arms, randomization strata of screening HbA1c(<8.0,>=8.0%),BMI(<30,>=30 kg/m^2),country as fixed effects, baseline HbA1c as covariate.
ANCOVA
<0.0001
Stepwise testing procedure applied to control type 1 error: lixisenatide (morning) compared with placebo (combined), if found statistically significant, then lixisenatide (evening) compared with placebo (combined).
Least squares (LS) mean difference
-0.48
Standard Error of the Mean
0.088
2-Sided
95
-0.657
-0.312
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Missing data was imputed using last observation carried forward (LOCF). Here, number of patients analyzed = patients with baseline and at least 1 post-baseline FPG assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
mmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Secondary
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline 2-hour PPG assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
mmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in Body Weight at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
kilogram
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Secondary
Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline plasma insulin assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
pmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Secondary
Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline PPI assessment during on-treatment period
Posted
Least Squares Mean
Standard Error
pmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in Fasting Proinsulin at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
pmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in 2-Hour Postprandial Proinsulin at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
pmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in Fasting C-Peptide at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline C-peptide assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
nmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in 2-Hour Postprandial C-Peptide at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline C-peptide assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
nmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Other Pre-specified
Change From Baseline in Glucose Excursion at Week 24
Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal teat. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucose excursion assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
mmol/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in Fasting Glucagon at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucagon assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
ng/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in 2-Hour Postprandial Glucagon at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.
Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucagon assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
ng/L
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo to lixisenatide.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Units
Counts
Participants
Secondary
Change From Baseline in Adiponectin at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline adiponectin assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
mcg/mL
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Secondary
Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24
Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin [micro unit per milliliter]) divided by (FPG [mmol/L] minus 3.5). Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HOMA-beta assessment during on-treatment period.
Posted
Least Squares Mean
Standard Error
% of normal beta cells function
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
Other Pre-specified
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.
Posted
Number
percentage of participants
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation, morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Other Pre-specified
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.
Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Posted
Number
participants
First dose of study drug up to 3 days after the last dose administration
ID
Title
Description
OG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo.
OG001
Placebo (Evening Injection)
2-step initiation evening regimen of volume matching placebo.
OG002
Placebo (Combined)
Secondary
Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period
Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) 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 (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG >270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8.5%. 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.
mITT population.
Posted
Number
percentage of participants
Baseline up to Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Secondary
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Posted
Number
percentage of participants
Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Secondary
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. 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.
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Posted
Number
percentage of participants
Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
OG001
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Time Frame
First dose of study drug up to 3 days after the last dose administration
Description
Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo (Morning Injection)
2-step initiation morning regimen of volume matching placebo.
2
85
45
85
EG001
Placebo (Evening Injection)
2-step initiation evening regimen of volume matching placebo.
9
85
50
85
EG002
Placebo (Combined)
Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.
11
170
95
170
EG003
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
21
255
182
255
EG004
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
26
255
169
255
EG005
Lixisenatide (Combined)
Included all patients who received 2-step initiation morning and evening regimen of lixisenatide.
47
510
351
510
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anal abscess
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG0030 affected255 at risk
EG0041 affected255 at risk
EG0051 affected510 at risk
Bacterial sepsis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Escherichia urinary tract infection
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Influenza
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Staphylococcal sepsis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Pancreatic carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Rectal cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Renal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Signet-ring cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0001 affected85 at risk
EG0010 affected85 at risk
EG0021 affected170 at risk
EG003
Thyroid neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Lymphadenitis
Blood and lymphatic system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected85 at risk
EG0010 affected85 at risk
EG0021 affected170 at risk
EG003
Obesity
Metabolism and nutrition disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Psychosomatic disease
Psychiatric disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Suicide attempt
Psychiatric disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Carpal tunnel syndrome
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Cerebral infarction
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Hypertensive encephalopathy
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Lacunar infarction
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Ruptured cerebral aneurysm
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Retinal haemorrhage
Eye disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Vitreous haemorrhage
Eye disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Angina unstable
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Atrioventricular block first degree
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Cardiomyopathy
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Coronary artery disease
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Ventricular extrasystoles
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Hypertensive crisis
Vascular disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Peripheral arterial occlusive disease
Vascular disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Bronchial obstruction
Respiratory, thoracic and mediastinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Abdominal adhesions
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Gastric haemorrhage
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected85 at risk
EG0010 affected85 at risk
EG0021 affected170 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Inguinal hernia, obstructive
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Rectal polyp
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Angioedema
Skin and subcutaneous tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Necrobiosis
General disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Pancreatic enzymes increased
Investigations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Dislocation of vertebra
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Joint injury
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0011 affected85 at risk
EG0021 affected170 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Skull fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Spinal cord injury
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Spinal fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Wrist fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Cardiac pacemaker insertion
Surgical and medical procedures
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Coronary artery bypass
Surgical and medical procedures
MedDRA 13.1
Non-systematic Assessment
EG0000 affected85 at risk
EG0010 affected85 at risk
EG0020 affected170 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Bronchitis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0008 affected85 at risk
EG0016 affected85 at risk
EG00214 affected170 at risk
EG00322 affected255 at risk
EG0046 affected255 at risk
EG00528 affected510 at risk
Gastroenteritis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0004 affected85 at risk
EG0014 affected85 at risk
EG0028 affected170 at risk
EG003
Influenza
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0005 affected85 at risk
EG0019 affected85 at risk
EG00214 affected170 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG00011 affected85 at risk
EG00115 affected85 at risk
EG00226 affected170 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0002 affected85 at risk
EG0013 affected85 at risk
EG0025 affected170 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0006 affected85 at risk
EG00110 affected85 at risk
EG00216 affected170 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0002 affected85 at risk
EG0015 affected85 at risk
EG0027 affected170 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 13.1
Non-systematic Assessment
Hypoglycaemia adverse event is based on investigator reported hypoglycaemia.
EG0000 affected85 at risk
EG0015 affected85 at risk
EG0025 affected170 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0005 affected85 at risk
EG0016 affected85 at risk
EG00211 affected170 at risk
EG003
Headache
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0008 affected85 at risk
EG00120 affected85 at risk
EG00228 affected170 at risk
EG003
Hypertension
Vascular disorders
MedDRA 13.1
Non-systematic Assessment
EG0003 affected85 at risk
EG0016 affected85 at risk
EG0029 affected170 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0002 affected85 at risk
EG0015 affected85 at risk
EG0027 affected170 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0002 affected85 at risk
EG0012 affected85 at risk
EG0024 affected170 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0003 affected85 at risk
EG0016 affected85 at risk
EG0029 affected170 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG00010 affected85 at risk
EG00110 affected85 at risk
EG00220 affected170 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected85 at risk
EG0010 affected85 at risk
EG0021 affected170 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0007 affected85 at risk
EG0019 affected85 at risk
EG00216 affected170 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0006 affected85 at risk
EG0013 affected85 at risk
EG0029 affected170 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0003 affected85 at risk
EG0012 affected85 at risk
EG0025 affected170 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0006 affected85 at risk
EG0016 affected85 at risk
EG00212 affected170 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected85 at risk
EG0012 affected85 at risk
EG0023 affected170 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0002 affected85 at risk
EG0011 affected85 at risk
EG0023 affected170 at risk
EG003
Fatigue
General disorders
MedDRA 13.1
Non-systematic Assessment
EG0003 affected85 at risk
EG0012 affected85 at risk
EG0025 affected170 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Point of Contact
Title
Organization
Phone
Extension
Email
Trial Transparency Team
Sanofi
Contact-us@sanofi.com
ID
Term
D003924
Diabetes Mellitus, Type 2
D006943
Hyperglycemia
Ancestor Terms
ID
Term
D003920
Diabetes Mellitus
D044882
Glucose Metabolism Disorders
D008659
Metabolic Diseases
D009750
Nutritional and Metabolic Diseases
D004700
Endocrine System Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C479460
lixisenatide
D008687
Metformin
Ancestor Terms
ID
Term
D001645
Biguanides
D006146
Guanidines
D000578
Amidines
D009930
Organic Chemicals
Browse Leaves
Not provided
Browse Branches
Not provided
54.7
± 9.7
141
BG003387
Male
BG00081
BG00198
BG002114
BG003293
228
BG003604
Race: Black
Title
Measurements
BG0004
BG0017
BG0026
BG00317
Race: Asian/Oriental
Title
Measurements
BG00011
BG00122
BG00220
BG00353
Race: Other
Title
Measurements
BG0000
BG0015
BG0021
BG0036
Ethnicity: Hispanic
Title
Measurements
BG00049
BG00196
BG00298
BG003243
Ethnicity: Non Hispanic
Title
Measurements
BG000121
BG001159
BG002157
BG003437
8.09
± 0.91
BG0038.06± 0.89
9.31
± 2.25
BG0039.40± 2.22
15.62
± 3.97
BG00215.46± 4.03
BG00315.53± 3.86
89.05
± 20.74
BG00389.71± 20.70
42.82
± 32.33
BG00245.21± 46.09
BG00343.38± 40.38
5.25
± 2.90
BG0025.25± 2.93
BG0035.34± 3.01
83.68
± 63.60
BG00277.90± 65.46
BG00379.53± 60.84
380.53
± 260.96
BG002378.67± 328.19
BG003378.30± 289.51
0.97
± 0.43
BG0020.94± 0.43
BG0030.94± 0.41
2.56
± 1.11
BG0022.42± 1.16
BG0032.48± 1.12
88.89
± 32.90
BG00288.53± 27.30
BG00388.51± 29.88
101.46
± 34.54
BG002100.90± 34.12
BG003101.21± 34.17
34.93
± 24.14
BG00232.35± 18.45
BG00333.16± 21.16
83.71
± 54.65
BG00277.19± 53.44
BG00381.15± 55.05
6.09
± 3.09
BG0025.80± 3.13
BG0035.87± 3.04
BG00232.47± 5.77
BG00332.91± 6.36
6.21
± 5.40
BG0036.11± 5.17(0.8 to 52.1)
3.68
± 3.90
BG0033.61± 3.59
1942.65
± 406.17
BG0031967.10± 430.22
No
Superiority or Other
OG000
OG002
To detect 0.5%(or 0.4%) difference between 1 lixisenatide arm and placebo(combined), 225 patients in lixisenatide arm, 170 in placebo(combined) would provide a power of 97% (or 87%) assuming common standard deviation=1.3% with 2-sided test at 5% significance. Statistical testing:2-sided at significance level=0.05. Analysis of co-variance(ANCOVA)included treatment arms, randomization strata of screening HbA1c(<8.0,>=8.0%),BMI(<30,>=30 kg/m^2),country as fixed effects, baseline HbA1c as covariate.
ANCOVA
<0.0001
Stepwise testing procedure applied to control type 1 error: lixisenatide (morning) compared with placebo (combined), if found statistically significant, then lixisenatide (evening) compared with placebo (combined).
LS mean difference
-0.37
Standard Error of the Mean
0.088
2-Sided
95
-0.540
-0.193
No
Superiority or Other
Units
Counts
Participants
OG000170
OG001253
OG002255
Title
Denominators
Categories
Title
Measurements
OG000-0.25± 0.166
OG001-1.19± 0.145
OG002-0.81± 0.146
OG00064
OG001200
Title
Denominators
Categories
Title
Measurements
OG000-1.41± 0.588
OG001-5.92± 0.415
Units
Counts
Participants
OG000168
OG001248
OG002249
Title
Denominators
Categories
Title
Measurements
OG000-1.64± 0.269
OG001-2.01± 0.234
OG002-2.02± 0.236
Units
Counts
Participants
OG000157
OG001237
OG002229
Title
Denominators
Categories
Title
Measurements
OG000-6.23± 3.254
OG001-5.09± 2.812
OG002-1.88± 2.862
OG00054
OG001181
Title
Denominators
Categories
Title
Measurements
OG000-25.67± 38.028
OG001-87.24± 24.885
OG00048
OG001154
Title
Denominators
Categories
Title
Measurements
OG000-3.78± 2.246
OG001-7.78± 1.414
OG00043
OG001129
Title
Denominators
Categories
Title
Measurements
OG000-6.83± 5.253
OG001-18.88± 3.406
OG00063
OG001192
Title
Denominators
Categories
Title
Measurements
OG000-0.13± 0.031
OG001-0.10± 0.020
OG00062
OG001193
Title
Denominators
Categories
Title
Measurements
OG000-0.20± 0.137
OG001-0.46± 0.097
OG00063
OG001198
Title
Denominators
Categories
Title
Measurements
OG000-0.76± 0.483
OG001-4.64± 0.340
OG00059
OG001191
Title
Denominators
Categories
Title
Measurements
OG000-13.53± 3.054
OG001-13.27± 2.074
OG00062
OG001191
Title
Denominators
Categories
Title
Measurements
OG000-12.79± 3.551
OG001-27.04± 2.467
Units
Counts
Participants
OG000155
OG001236
OG002227
Title
Denominators
Categories
Title
Measurements
OG0000.54± 0.183
OG0010.55± 0.159
OG0020.58± 0.160
OG002
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
Units
Counts
Participants
OG000157
OG001235
OG002226
Title
Denominators
Categories
Title
Measurements
OG000-4.16± 2.823
OG0017.96± 2.450
OG0024.80± 2.486
Units
Counts
Participants
OG000168
OG001248
OG002249
Title
Denominators
Categories
Title
Measurements
OG00011.3
OG00114.9
OG00219.3
Included all patients who received 2-step initiation, morning and evening regimen of volume matching placebo.
OG003
Lixisenatide (Morning Injection)
2-step initiation morning regimen of lixisenatide.
OG004
Lixisenatide (Evening Injection)
2-step initiation evening regimen of lixisenatide.
OG005
Lixisenatide (Combined)
Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.