Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 29 of 61 for:    Lixisenatide

Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (GetGoal-M-Asia)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01169779
Recruitment Status : Completed
First Posted : July 26, 2010
Results First Posted : October 13, 2016
Last Update Posted : October 13, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: Lixisenatide (AVE0010)
Drug: Placebo
Device: Pen auto-injector
Drug: Metformin
Drug: Sulfonylurea
Enrollment 391
Recruitment Details The study was conducted at 35 centers in 4 countries between July 21, 2010 and December 22, 2011.
Pre-assignment Details A total of 655 patients were screened of which 264 (40.3%) 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 391 patients were randomized.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description 1-step initiation regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) subcutaneously for 2 weeks, followed by 20 mcg QD up to Week 24. 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, followed by 20 mcg QD up to Week 24.
Period Title: Overall Study
Started 195 [1] 196
Treated/Safety Population 194 [2] 196
Modified Intent-to-Treat(mITT)Population 193 [3] 195
Subgroup for Standardized Meal Test 130 [4] 121
Completed 184 179
Not Completed 11 17
Reason Not Completed
Adverse Event             3             11
Lack of Efficacy             1             0
Protocol Violation             1             1
Withdrawal by Subject             3             2
Familial and personal reasons             3             3
[1]
Randomized.
[2]
All patients who were exposed to at least 1 dose, regardless of amount of treatment administered.
[3]
All patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment.
[4]
Patients at selected sites where standardized meal test was performed.
Arm/Group Title Placebo Lixisenatide Total
Hide Arm/Group Description 1-step initiation regimen of volume matching placebo: 10 mcg QD subcutaneously for 2 weeks, followed by 20 mcg QD up to Week 24. 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, followed by 20 mcg QD up to Week 24. Total of all reporting groups
Overall Number of Baseline Participants 194 196 390
Hide Baseline Analysis Population Description
Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 194 participants 196 participants 390 participants
55.1  (10.5) 54.5  (10.3) 54.8  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 194 participants 196 participants 390 participants
Female
103
  53.1%
95
  48.5%
198
  50.8%
Male
91
  46.9%
101
  51.5%
192
  49.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Race: Asian/Oriental Number Analyzed 194 participants 196 participants 390 participants
194 196 390
Glycosylated Hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of hemoglobin
Number Analyzed 194 participants 196 participants 390 participants
7.85  (0.71) 7.95  (0.81) 7.90  (0.76)
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  Millimole per liter (mmol/L)
Number Analyzed 194 participants 196 participants 390 participants
8.74  (1.83) 8.84  (2.12) 8.79  (1.98)
2-Hour Postprandial Plasma Glucose (PPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 194 participants 196 participants 390 participants
17.19  (4.06) 16.07  (3.77) 16.65  (3.95)
[1]
Measure Description: The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Number of patients analyzed = 130 and 121 for Placebo and Lixisenatide treatment arm, respectively, as meal challenge test was performed at selected sites only.
Glucose Excursion   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 194 participants 196 participants 390 participants
8.14  (3.11) 7.12  (3.21) 7.65  (3.20)
[1]
Measure Description: Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the meal test, before study drug administration. Number of patients analyzed = 130 and 121 for Placebo and Lixisenatide treatment arm, respectively, as meal challenge test was performed at selected sites only.
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 194 participants 196 participants 390 participants
72.74  (13.64) 73.18  (13.93) 72.96  (13.77)
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 194 participants 196 participants 390 participants
6.84  (4.80) 6.45  (4.64) 6.64  (4.72)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 194 participants 196 participants 390 participants
27.08  (3.75) 26.75  (3.86) 26.91  (3.80)
[1]
Measure Description: BMI was calculated by dividing body weight by the height squared.
Metformin Daily Dose  
Mean (Standard Deviation)
Unit of measure:  Milligram (mg) per day
Number Analyzed 194 participants 196 participants 390 participants
1363.4  (221.9) 1369.9  (219.9) 1366.7  (220.7)
Number of Patients With Sulfonylurea use at Baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 194 participants 196 participants 390 participants
Yes 92 82 174
No 102 114 216
1.Primary Outcome
Title Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Hide Description Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 188 185
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-0.47  (0.104) -0.83  (0.102)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lixisenatide
Comments To detect a difference of 0.5% in change in HbA1c at Week 24 between lixisenatide arm and placebo arm, 190 patients per group would provide a power of 96% assuming common standard deviation of 1.3% with 2-sided test at 5% significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments 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%), sulfonylurea use (Yes,No), country as fixed effects, baseline HbA1c as covariate.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.551 to -0.162
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.099
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Hide Description Change was calculated by subtracting Baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 191 190
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.21  (0.200) -0.69  (0.197)
3.Secondary Outcome
Title Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
Hide Description The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting Baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test. 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.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 116 107
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-1.33  (0.376) -5.61  (0.393)
4.Secondary Outcome
Title Change From Baseline in Body Weight at Week 24
Hide Description Change was calculated by subtracting Baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 191 188
Least Squares Mean (Standard Error)
Unit of Measure: kilogram
-1.24  (0.273) -1.50  (0.267)
5.Secondary Outcome
Title Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
Hide Description The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 188 185
Measure Type: Number
Unit of Measure: percentage of participants
38.8 53.0
6.Secondary Outcome
Title Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
Hide Description The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 188 185
Measure Type: Number
Unit of Measure: percentage of participants
18.1 32.4
7.Secondary Outcome
Title Change From Baseline in Glucose Excursion at Week 24
Hide Description 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 the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup for standardized meal test. 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.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 116 106
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.79  (0.340) -4.78  (0.356)
8.Secondary Outcome
Title Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
Hide Description 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 >250 milligram/deciliter (mg/dL) (13.9 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >220 mg/dL (12.2 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 on-treatment assessment for at least 1 efficacy variable, were required.
Time Frame Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 193 195
Measure Type: Number
Unit of Measure: percentage of participants
6.7 3.6
9.Other Pre-specified Outcome
Title Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
Hide Description The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 191 188
Measure Type: Number
Unit of Measure: percentage of participants
14.7 19.7
10.Other Pre-specified Outcome
Title Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia
Hide Description Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.
Time Frame First dose of study drug up to 3 days after the last dose administration
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description:
1-step initiation regimen of volume matching placebo.
1-step initiation regimen of lixisenatide.
Overall Number of Participants Analyzed 194 196
Measure Type: Number
Unit of Measure: participants
Symptomatic hypoglycemia 5 11
Severe symptomatic hypoglycemia 0 0
Time Frame First dose of study drug up to 3 days after the last dose administration
Adverse Event Reporting Description Median exposure to study treatment was 169 days for both treatment arms. 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.
 
Arm/Group Title Placebo Lixisenatide
Hide Arm/Group Description 1-step initiation regimen of volume matching placebo. 1-step initiation regimen of lixisenatide.
All-Cause Mortality
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   4/194 (2.06%)   3/196 (1.53%) 
Cardiac disorders     
Acute myocardial infarction * 1  0/194 (0.00%)  1/196 (0.51%) 
Gastrointestinal disorders     
Abdominal pain * 1  0/194 (0.00%)  1/196 (0.51%) 
Hepatobiliary disorders     
Hepatic function abnormal * 1  1/194 (0.52%)  0/196 (0.00%) 
Immune system disorders     
Anaphylactic shock * 1  0/194 (0.00%)  1/196 (0.51%) 
Nervous system disorders     
Cerebral infarction * 1  0/194 (0.00%)  1/196 (0.51%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  1/194 (0.52%)  0/196 (0.00%) 
Prostatitis * 1  1/194 (0.52%)  0/196 (0.00%) 
Vascular disorders     
Hypertension * 1  1/194 (0.52%)  0/196 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Lixisenatide
Affected / at Risk (%) Affected / at Risk (%)
Total   46/194 (23.71%)   80/196 (40.82%) 
Gastrointestinal disorders     
Nausea * 1  5/194 (2.58%)  32/196 (16.33%) 
Vomiting * 1  2/194 (1.03%)  15/196 (7.65%) 
Infections and infestations     
Upper respiratory tract infection * 1  8/194 (4.12%)  12/196 (6.12%) 
Investigations     
Blood glucose decreased * 1  5/194 (2.58%)  10/196 (5.10%) 
Metabolism and nutrition disorders     
Hyperuricaemia * 1  10/194 (5.15%)  7/196 (3.57%) 
Hypoglycaemia * 1 [1]  9/194 (4.64%)  18/196 (9.18%) 
Nervous system disorders     
Dizziness * 1  8/194 (4.12%)  17/196 (8.67%) 
Renal and urinary disorders     
Diabetic nephropathy * 1  13/194 (6.70%)  13/196 (6.63%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
[1]
Hypoglycaemia adverse event is based on investigator reported hypoglycaemia.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01169779     History of Changes
Other Study ID Numbers: EFC11321
U1111-1116-8938 ( Other Identifier: UTN )
First Submitted: July 23, 2010
First Posted: July 26, 2010
Results First Submitted: August 18, 2016
Results First Posted: October 13, 2016
Last Update Posted: October 13, 2016