GLP-1 Receptor Agonist Lixisenatide in Patients With Type... | NCT00763451 | Trialant
NCT00763451
Sponsor
Sanofi
Status
Completed
Last Update Posted
Dec 14, 2016Estimated
Enrollment
484Actual
Phase
Phase 3
Conditions
Diabetes Mellitus, Type 2
Interventions
Lixisenatide (AVE0010)
Placebo
Pen auto-injector
Metformin
Countries
United States
Brazil
Chile
Colombia
Estonia
Germany
Italy
Lithuania
Malaysia
Mexico
Philippines
Poland
Romania
Slovakia
Ukraine
Protocol Section
Identification Module
NCT ID
NCT00763451
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
EFC10743
Secondary IDs
ID
Type
Description
Link
2008-001002-16
EudraCT Number
Brief Title
GLP-1 Receptor Agonist Lixisenatide 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 in Two Titration Regimens on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin
Acronym
GETGOAL-F1
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
Sep 2008
Primary Completion Date
Jan 2011Actual
Completion Date
Jan 2011Actual
First Submitted Date
Sep 30, 2008
First Submission Date that Met QC Criteria
Sep 30, 2008
First Posted Date
Oct 1, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 18, 2016
Results First Submitted that Met QC Criteria
Oct 21, 2016
Results First Posted Date
Dec 14, 2016Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Feb 21, 2012
Certification/Extension First Submitted that Passed QC Review
Feb 21, 2012
Certification/Extension First Posted Date
Feb 23, 2012Estimated
Last Update Submitted Date
Oct 21, 2016
Last Update Posted Date
Dec 14, 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 when added to metformin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction when it is used in two steps dose titration regimen at Week 24.
Secondary objectives are to assess the effects of lixisenatide when added to metformin on glycemic control in comparison to placebo in terms of HbA1c reduction when it is used in a one-step dose titration regimen, the percentage of patients with HbA1c less than 7 percent or less than or equal to 6.5%, body weight, fasting plasma glucose (FPG); to assess the safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.
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 patients.
Conditions Module
Conditions
Diabetes Mellitus, Type 2
Keywords
hyperglycemia, GLP-1
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
484Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Lixisenatide (Two-Step Titration)
Experimental
2-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
Drug: Lixisenatide (AVE0010)
Device: Pen auto-injector
Drug: Metformin
Lixisenatide (One-Step Titration)
Experimental
1-step initiation regimen of lixisenatide: 10 mcg QD for 2 weeks, then 20 mcg QD up to the end of treatment.
Drug: Lixisenatide (AVE0010)
Device: Pen auto-injector
Drug: Metformin
Placebo (Two-Step Titration)
Placebo Comparator
2-step initiation regimen of volume matching placebo: 10 mcg QD for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
Drug: Placebo
Device: Pen auto-injector
Drug: Metformin
Placebo (One-Step Titration)
Placebo Comparator
1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, then 20 mcg QD up to the 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 breakfast.
Lixisenatide (One-Step Titration)
Lixisenatide (Two-Step Titration)
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 mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
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
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.
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/day for at least 3 months prior to screening visit
Exclusion Criteria:
HbA1c less than (<) 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 less than or equal to (<)20 kilogram per square meter (kg/m^2)
Weight change of more than 5 kg during the 3 months preceding the screening visit
History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
Known history of drug or alcohol abuse within 6 months prior to the time of screening
Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic or diastolic blood pressure >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
Laboratory findings at the time of screening: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP): >2 times upper limit of the normal (ULN) laboratory range; amylase and/or lipase: >3 times ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb) and positive serum pregnancy test in females of childbearing potential
Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram (ECG) 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 oral or injectable antidiabetic or hypoglycemic agents other than metformin (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, rimonabant, exenatide, dipeptidylpeptidase-4 (DPP-IV) inhibitor, insulin) within 3 months prior to the time of screening
Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one 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 any 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
Bolli GB, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Wu Y, Hanefeld M. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med. 2014 Feb;31(2):176-84. doi: 10.1111/dme.12328. Epub 2013 Oct 24.
A total of 884 patients were screened of which 400 (45.2%) 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 percent [%] and less than or equal to 10%). A total of 484 patients were randomized.
Recruitment Details
The study was conducted at 75 centers in 15 countries between September 29, 2008 and January 27, 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 (Two-Step Titration)
2-step initiation 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 the end of treatment.
FG001
Placebo (One-Step Titration)
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
Placebo
Drug
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
Placebo (One-Step Titration)
Placebo (Two-Step Titration)
Pen auto-injector
Device
Lixisenatide (One-Step Titration)
Lixisenatide (Two-Step Titration)
Placebo (One-Step Titration)
Placebo (Two-Step Titration)
OptiClik®
Metformin
Drug
Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
Lixisenatide (One-Step Titration)
Lixisenatide (Two-Step Titration)
Placebo (One-Step Titration)
Placebo (Two-Step Titration)
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
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
Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
Routine fasting self-measured 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
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, for up to 112 weeks
Ambery P, Donner TW, Biswas N, Donaldson J, Parkin J, Dayan CM. Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. Diabet Med. 2014 Apr;31(4):399-402. doi: 10.1111/dme.12361. Epub 2013 Dec 6.
1-step initiation regimen of volume matching placebo: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment.
FG002
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
FG003
Lixisenatide (One-Step Titration)
1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment.
FG00080 subjectsRandomized.
FG00182 subjects
FG002161 subjects
FG003161 subjects
Treated/Safety Population
FG00079 subjectsAll patients who were exposed to at least 1 dose, regardless of amount of treatment administered.
FG00181 subjects
FG002161 subjects
FG003161 subjects
Modified Intent-to-Treat(mITT)Population
FG00079 subjectsAll patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment.
FG00180 subjects
FG002160 subjects
FG003160 subjects
COMPLETED
FG00067 subjects
FG00160 subjects
FG002121 subjects
FG003131 subjects
NOT COMPLETED
FG00013 subjects
FG00122 subjects
FG00240 subjects
FG00330 subjects
Type
Comment
Reasons
Adverse Event
FG0004 subjects
FG0016 subjects
FG00219 subjects
FG00314 subjects
Lack of Efficacy
FG0001 subjects
FG0014 subjects
FG0023 subjects
FG0032 subjects
Withdrawal by Subject
FG0001 subjects
FG0016 subjects
FG0029 subjects
FG0037 subjects
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
Poor Compliance to Protocol
FG0001 subjects
FG0011 subjects
FG0022 subjects
FG0032 subjects
Familial and Personal Reasons
FG0005 subjects
FG0013 subjects
FG0025 subjects
FG0034 subjects
Randomized but not Treated
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
Study Site Reason
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0031 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 (Two-step Titration)
2-step initiation 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 the end of treatment.
BG001
Placebo (One-step Titration)
1-step initiation regimen of volume matching placebo: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment.
BG002
Lixisenatide (Two-step Titration)
2-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment.
BG003
Lixisenatide (One-step Titration)
1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00079
BG00181
BG002161
BG003161
BG004482
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
BG00058.9± 8.8
BG00157.5± 10.8
BG00254.6± 8.9
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00043
BG00145
BG002
Race/Ethnicity, Customized
Number
participants
Title
Denominators
Categories
Race: Caucasian/White
Title
Measurements
BG00072
BG00176
BG002
Glycosylated Hemoglobin (HbA1c)
Mean
Standard Deviation
percentage of hemoglobin
Title
Denominators
Categories
Title
Measurements
BG0008.03± 0.81
BG0018.02± 0.84
BG002
Fasting Plasma Glucose (FPG)
Mean
Standard Deviation
millimole per liter (mmol/L)
Title
Denominators
Categories
Title
Measurements
BG0009.60± 2.06
BG0019.31± 1.82
BG002
Body Weight
Mean
Standard Deviation
kilogram
Title
Denominators
Categories
Title
Measurements
BG00087.45± 16.32
BG00188.28± 18.43
BG002
Duration of Diabetes
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG0006.68± 5.33
BG0015.77± 4.00
BG002
Body Mass Index (BMI)
BMI was calculated by dividing body weight (kilogram) by the height (meter) squared.
Mean
Standard Deviation
kilogram per square meter (kg/m^2)
Title
Denominators
Categories
Title
Measurements
BG00032.38± 5.04
BG00132.35± 5.86
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 mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
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 regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
OG002
Lixisenatide (One-Step Titration)
1-step initiation regimen of lixisenatide.
Units
Counts
Participants
OG000158
OG001152
OG002156
Title
Denominators
Categories
Title
Measurements
OG000-0.42± 0.099
OG001-0.83± 0.099
OG002-0.92± 0.101
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 a difference of 0.5% (or 0.4%) in absolute change from baseline in HbA1c at Week 24 between 1 lixisenatide arm and placebo (combined), 150 patients per group would provide a power of 91% (or 75%) assuming common standard deviation of 1.3% with 2-sided test at 5% significance level.
Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (<8.0,>=8.0%) and screening BMI (<30,>=30 kg/m^2), country as fixed effects, baseline HbA1c as covariate.
ANCOVA
Threshold for significance at 0,05 level
<0.0001
Stepwise testing procedure applied to control type 1 error: Lixisenatide (2-step titration) was compared with Placebo (combined), if found statistically significant, then Lixisenatide (1-step titration) arm compared with Placebo (combined).
Least squares (LS) mean difference
-0.41
Standard Error of the Mean
0.089
2-Sided
95
-0.583
-0.232
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.The "Placebo (Two-step Titration)"and"Placebo (One-step Titration)"Arms/Groups were combined as pre-specified in the study protocol
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 regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
OG002
Lixisenatide (One-Step Titration)
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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Posted
Least Squares Mean
Standard Error
kilogram
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
OG002
Lixisenatide (One-Step Titration)
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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Posted
Number
percentage of participants
Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
OG002
Lixisenatide (One-Step Titration)
1-step initiation 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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Posted
Number
percentage of participants
Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
OG002
Lixisenatide (One-Step Titration)
1-step initiation regimen of lixisenatide.
Secondary
Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
Routine fasting self-measured 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. The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Posted
Number
percentage of participants
Baseline up to Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
OG002
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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Posted
Number
percentage of participants
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
OG002
Lixisenatide (One-Step Titration)
1-step initiation 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.The "Placebo (Two-step Titration)" and "Placebo (One-step Titration)" Arms/Groups were combined as pre-specified in the study protocol
Posted
Number
participants
First dose of study drug up to 3 days after the last dose administration, for up to 112 weeks
ID
Title
Description
OG000
Placebo (Combined)
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
OG001
Lixisenatide (Two-Step Titration)
2-step initiation regimen of lixisenatide.
Time Frame
First dose of study drug up to 3 days after the last dose administration, for up to 112 weeks
Description
Median exposure to study treatment was 567, 588 and 589 days in lixisenatide two step titration, one step titration and placebo combined 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 (Two-step Titration)
2-step initiation regimen of volume matching placebo.
13
79
51
79
EG001
Placebo (One-step Titration)
1-step initiation regimen of volume matching placebo.
9
81
53
81
EG002
Placebo (Combined)
Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo.
22
160
104
160
EG003
Lixisenatide (Two-step Titration)
2-step initiation regimen of lixisenatide.
21
161
119
161
EG004
Lixisenatide One-step Titration
1-step initiation regimen of lixisenatide.
16
161
101
161
EG005
Lixisenatide (Combined)
Included all patients who received 2-step initiation regimen of lixisenatide and 1-step initiation regimen of lixisenatide.
37
322
220
322
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Appendicitis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG0030 affected161 at risk
EG0041 affected161 at risk
EG0051 affected322 at risk
Bronchitis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Dengue fever
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Hepatitis B
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Lobar pneumonia
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Peritonsillar abscess
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0011 affected81 at risk
EG0022 affected160 at risk
EG003
Septic shock
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Soft tissue infection
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Bladder cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Ovarian cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Pancreatic carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Renal neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Goitre
Endocrine disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Diabetes mellitus
Metabolism and nutrition disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Depression
Psychiatric disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Cerebral infarction
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Coma
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Diabetic neuropathy
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Haemorrhagic stroke
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Polyneuropathy
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Ruptured cerebral aneurysm
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Retinal detachment
Eye disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Adams-Stokes syndrome
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Angina unstable
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Coronary artery disease
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Coronary artery stenosis
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Hypertension
Vascular disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Irritable bowel syndrome
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Dermatitis allergic
Skin and subcutaneous tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Arthropathy
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Osteochondrosis
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Blood calcitonin increased
Investigations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Pancreatic enzymes increased
Investigations
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Ankle fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Incisional hernia
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Meniscus lesion
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Multiple injuries
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Spinal fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Sternal fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Wrist fracture
Injury, poisoning and procedural complications
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0010 affected81 at risk
EG0020 affected160 at risk
EG003
Coronary arterial stent insertion
Surgical and medical procedures
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 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
EG0006 affected79 at risk
EG0017 affected81 at risk
EG00213 affected160 at risk
EG0033 affected161 at risk
EG0047 affected161 at risk
EG00510 affected322 at risk
Gastroenteritis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0007 affected79 at risk
EG0012 affected81 at risk
EG0029 affected160 at risk
EG003
Influenza
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0009 affected79 at risk
EG0019 affected81 at risk
EG00218 affected160 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG00013 affected79 at risk
EG0018 affected81 at risk
EG00221 affected160 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0006 affected79 at risk
EG0016 affected81 at risk
EG00212 affected160 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0015 affected81 at risk
EG0029 affected160 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 13.1
Non-systematic Assessment
EG0006 affected79 at risk
EG0015 affected81 at risk
EG00211 affected160 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 13.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0010 affected81 at risk
EG0024 affected160 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 13.1
Non-systematic Assessment
Hypoglycaemia adverse event is based on investigator reported hypoglycaemia.
EG0008 affected79 at risk
EG0015 affected81 at risk
EG00213 affected160 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG00011 affected79 at risk
EG00110 affected81 at risk
EG00221 affected160 at risk
EG003
Headache
Nervous system disorders
MedDRA 13.1
Non-systematic Assessment
EG00011 affected79 at risk
EG0019 affected81 at risk
EG00220 affected160 at risk
EG003
Hypertension
Vascular disorders
MedDRA 13.1
Non-systematic Assessment
EG0002 affected79 at risk
EG00110 affected81 at risk
EG00212 affected160 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0003 affected79 at risk
EG0014 affected81 at risk
EG0027 affected160 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0003 affected79 at risk
EG0010 affected81 at risk
EG0023 affected160 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG00010 affected79 at risk
EG00111 affected81 at risk
EG00221 affected160 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0010 affected81 at risk
EG0024 affected160 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0008 affected79 at risk
EG0015 affected81 at risk
EG00213 affected160 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 13.1
Non-systematic Assessment
EG0001 affected79 at risk
EG0010 affected81 at risk
EG0021 affected160 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0009 affected79 at risk
EG0015 affected81 at risk
EG00214 affected160 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0008 affected79 at risk
EG0013 affected81 at risk
EG00211 affected160 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0014 affected81 at risk
EG0028 affected160 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0012 affected81 at risk
EG0026 affected160 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Non-systematic Assessment
EG0005 affected79 at risk
EG0013 affected81 at risk
EG0028 affected160 at risk
EG003
Asthenia
General disorders
MedDRA 13.1
Non-systematic Assessment
EG0000 affected79 at risk
EG0011 affected81 at risk
EG0021 affected160 at risk
EG003
Oedema peripheral
General disorders
MedDRA 13.1
Non-systematic Assessment
EG0004 affected79 at risk
EG0013 affected81 at risk
EG0027 affected160 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
55.4
± 8.9
BG00456.1± 9.3
89
BG00390
BG004267
Male
BG00036
BG00136
BG00272
BG00371
BG004215
146
BG003141
BG004435
Race: Black
Title
Measurements
BG0000
BG0011
BG0022
BG0031
BG0044
Race: Asian/Oriental
Title
Measurements
BG0005
BG0014
BG00211
BG00313
BG00433
Race: Other
Title
Measurements
BG0002
BG0010
BG0022
BG0036
BG00410
Ethnicity: Hispanic
Title
Measurements
BG00024
BG00122
BG00255
BG00344
BG004145
Ethnicity: Non Hispanic
Title
Measurements
BG00055
BG00159
BG002106
BG003117
BG004337
8.10
± 0.88
BG0037.99± 0.87
BG0048.04± 0.86
9.54
± 2.50
BG0039.56± 2.02
BG0049.52± 2.17
87.41
± 16.90
BG00390.21± 18.95
BG00488.50± 17.77
6.01
± 4.60
BG0035.77± 3.85
BG0046.00± 4.40
BG00232.06± 4.84
BG00332.99± 5.80
BG00432.47± 5.38
No
Superiority or Other
OG000
OG002
To detect a difference of 0.5% (or 0.4%) in absolute change from baseline in HbA1c at Week 24 between 1 lixisenatide arm and placebo (combined), 150 patients per group would provide a power of 91% (or 75%) assuming common standard deviation of 1.3% with 2-sided test at 5% significance level.
Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (<8.0,>=8.0%) and screening BMI (<30,>=30 kg/m^2), country as fixed effects, baseline HbA1c as covariate.
ANCOVA
Threshold for significance at 0,05 level
<0.0001
Stepwise testing procedure applied to control type 1 error: Lixisenatide (2-step titration) was compared with Placebo (combined), if found statistically significant, then Lixisenatide (1-step titration) arm compared with Placebo (combined).