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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-002090-36 | EudraCT Number | ||
| U1111-1121-7111 | Other Identifier | UTN |
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Primary Objective:
Secondary Objectives:
To compare insulin glargine/lixisenatide FRC versus insulin glargine over 24 weeks on:
To assess safety and tolerability of insulin glargine/lixisenatide FRC.
Approximately 27 weeks including a 24-week treatment period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin glargine/Lixisenatide Fixed Ratio Combination (FRC) | Experimental | FRC injected once daily (QD) for 24 weeks. Dose individually adjusted. |
|
| Insulin glargine | Active Comparator | Insulin glargine QD for 24 weeks. Dose individually adjusted. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin glargine /lixisenatide Fixed Ratio Combination | Drug | FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using pen-type injector (Tactipen®): 100 U/ml insulin glargine and 50 mcg Lixisenatide (ratio of 2 U/1 mcg). The initial dose was 10 U/5 mcg and then dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in HbA1c From Baseline to Week 24 | Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of investigational medicinal product (IMP). | Baseline, Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 2-hour Postprandial Plasma Glucose (PPG) From Baseline to Week 24 | The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. |
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Inclusion criteria:
Exclusion criteria:
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Site Number 840408 | Little Rock | Arkansas | 72205 | United States | ||
| Investigational Site Number 840412 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27284114 | Result | Rosenstock J, Diamant M, Aroda VR, Silvestre L, Souhami E, Zhou T, Perfetti R, Fonseca V; LixiLan PoC Study Group. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial. Diabetes Care. 2016 Sep;39(9):1579-86. doi: 10.2337/dc16-0046. Epub 2016 Jun 9. |
| Label | URL |
|---|---|
| Related Info | View source |
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A total of 323 participants were randomized in 1:1 ratio to insulin glargine/lixisenatide fixed ratio combination (FRC) and insulin glargine arms, stratified by screening HbA1c values (<8% or ≥8%) and screening body mass index (BMI) values (<30 kg/m^2, ≥30 kg/m^2).
The study was conducted at 70 centers in 13 countries. A total of 520 participants were screened between November 21, 2011 and June 08, 2012. Out of 520 participants, 197 were screen failure; main reason for screen failure was that glycosylated hemoglobin (HbA1c) values were out of the protocol defined range.
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| ID | Title | Description |
|---|---|---|
| FG000 | Insulin Glargine/Lixisenatide Fixed Ratio Combination | FRC injected subcutaneously once daily (QD) for 24 weeks. Dose individually adjusted. |
| FG001 | Insulin Glargine | Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Insulin glargine | Drug | Insulin glargine (100 U/ml) was self-administered by SC injection before breakfast using pen-type injector (Lantus® Solostar®). The initial daily dose of insulin glargine was 10 U and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L). |
|
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| Metformin (Background drug) | Drug | Pharmaceutical form: Tablet; Route of administration: oral administration. To be kept at stable dose (≥1.5 g/day) throughout the study. |
|
| Baseline, Week 24 |
| Change in 2-hour Plasma Glucose Excursion From Baseline to Week 24 | 2-hour plasma glucose excursion = 2-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | Baseline, Week 24 |
| Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profiles From Baseline to Week 24 | Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, over a single day, once in a week before baseline, before visit Week 12 and before visit Week 24 and the average value across the profiles performed in the week before a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | Baseline, Week 24 |
| Change in Body Weight From Baseline to Week 24 | Change in body weight was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 3 days after the last injection of IMP. | Baseline, Week 24 |
| Average Daily Insulin Glargine Dose at Week 24 | Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | Week 24 |
| Change in FPG From Baseline to Week 24 | Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 1 day after the last injection of IMP. | Baseline, Week 24 |
| Percentage of Participants Requiring Rescue Therapy During 24-week Treatment Period | Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceed the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) were performed. Threshold values from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8%. | Baseline up to Week 24 |
| Percentage of Participants With HbA1c ≤6.5 % or <7.0 % at Week 24 | On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP. | Week 24 |
| Change in 30-minute and 1-hour PPG From Baseline to Week 24 | The 30 minute and 1-hour PPG test measured blood glucose 30 minutes and 1-hour after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | Baseline, Week 24 |
| Change in 30 Minute and 1-hour Plasma Glucose Excursion From Baseline to Week 24 | 30-minute and 1-hour plasma glucose excursion = 30-minute and 1-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | Baseline, Week 24 |
| Percentage of Participants Reaching HbA1c <7% at Week 24 With no Documented Symptomatic Hypoglycemia During 24-week Treatment Period | Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L). Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one documented symptomatic hypoglycemia before the introduction of rescue medication and up to 1 day after the last injection of IMP. Otherwise, they were counted as missing data. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP. | Baseline up to Week 24 |
| Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 | Participants without any post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (for HbA1c and body weight) was available and showed non-response. Otherwise, they were counted as missing data. | Week 24 |
| Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia | Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes were associated with sufficient neuroglycopenia to induce seizure, unconsciousness or coma. All episodes in which neurological impairment was severe enough to prevent self-treatment and which were thought to place participants at risk for injury to themselves or others. | First dose of study drug up to 3 days after the last dose administration (maximum of 219 days) |
| Paramount |
| California |
| 90723 |
| United States |
| Investigational Site Number 840401 | Larenceville | Georgia | 30045 | United States |
| Investigational Site Number 840417 | Roswell | Georgia | 30076 | United States |
| Investigational Site Number 840403 | Lexington | Kentucky | 40504 | United States |
| Investigational Site Number 840404 | Hyattsville | Maryland | 20782 | United States |
| Investigational Site Number 840405 | Rockville | Maryland | 20852 | United States |
| Investigational Site Number 840411 | Las Vegas | Nevada | 89148 | United States |
| Investigational Site Number 840415 | West Seneca | New York | 14224 | United States |
| Investigational Site Number 840402 | Norman | Oklahoma | 73069 | United States |
| Investigational Site Number 840407 | Medford | Oregon | 97504 | United States |
| Investigational Site Number 840413 | Durham | Pennsylvania | 27713 | United States |
| Investigational Site Number 840410 | Dallas | Texas | 75230 | United States |
| Investigational Site Number 840414 | Renton | Washington | 98055 | United States |
| Investigational Site Number 152404 | Santiago | 7500347 | Chile |
| Investigational Site Number 152405 | Santiago | 7500347 | Chile |
| Investigational Site Number 152403 | Santiago | 7500710 | Chile |
| Investigational Site Number 152401 | Santiago | 7980378 | Chile |
| Investigational Site Number 152402 | Santiago | 8320000 | Chile |
| Investigational Site Number 203403 | Nový Jičín | 74101 | Czechia |
| Investigational Site Number 203401 | Pilsen | 32600 | Czechia |
| Investigational Site Number 203402 | Prague | 12808 | Czechia |
| Investigational Site Number 203405 | Prague | 18100 | Czechia |
| Investigational Site Number 208401 | København NV | 2400 | Denmark |
| Investigational Site Number 208404 | Køge | 4600 | Denmark |
| Investigational Site Number 208402 | Slagelse | 4200 | Denmark |
| Investigational Site Number 208403 | Svendborg | 5700 | Denmark |
| Investigational Site Number 250402 | Narbonne | 11018 | France |
| Investigational Site Number 250404 | Poitiers | 86021 | France |
| Investigational Site Number 250401 | Vandœuvre-lès-Nancy | 54511 | France |
| Investigational Site Number 276401 | Dresden | 01307 | Germany |
| Investigational Site Number 276402 | Ludwigshafen | 67059 | Germany |
| Investigational Site Number 276403 | Oberhausen | 46045 | Germany |
| Investigational Site Number 348401 | Balatonfüred | 8230 | Hungary |
| Investigational Site Number 348405 | Budapest | 1041 | Hungary |
| Investigational Site Number 348406 | Budapest | 1212 | Hungary |
| Investigational Site Number 348404 | Debrecen | 4043 | Hungary |
| Investigational Site Number 348402 | Szeged | 6720 | Hungary |
| Investigational Site Number 348403 | Szeged | 6722 | Hungary |
| Investigational Site Number 440401 | Kaunas | LT-49456 | Lithuania |
| Investigational Site Number 440402 | Kaunas | LT-51270 | Lithuania |
| Investigational Site Number 440403 | Kėdainiai | LT-57164 | Lithuania |
| Investigational Site Number 440404 | Klaipėda | LT-92304 | Lithuania |
| Investigational Site Number 484404 | Acapulco | 39670 | Mexico |
| Investigational Site Number 484401 | Cuernavaca | 62250 | Mexico |
| Investigational Site Number 484405 | Durango | 34270 | Mexico |
| Investigational Site Number 484402 | Guadalajara | 44210 | Mexico |
| Investigational Site Number 484403 | Guadalajara | 44656 | Mexico |
| Investigational Site Number 616405 | Bialystok | 15-435 | Poland |
| Investigational Site Number 616406 | Gdansk | 80-847 | Poland |
| Investigational Site Number 616403 | Krakow | 31-548 | Poland |
| Investigational Site Number 616407 | Lodz | 94-074 | Poland |
| Investigational Site Number 616404 | Puławy | 24-100 | Poland |
| Investigational Site Number 616402 | Szczecin | 70-506 | Poland |
| Investigational Site Number 616401 | Warsaw | 02-507 | Poland |
| Investigational Site Number 642402 | Brasov | 500365 | Romania |
| Investigational Site Number 642403 | Bucharest | 020475 | Romania |
| Investigational Site Number 642405 | Iași | 700547 | Romania |
| Investigational Site Number 642401 | Oradea | 410169 | Romania |
| Investigational Site Number 642406 | Târgu Mureş | 540142 | Romania |
| Investigational Site Number 642404 | Timișoara | 300133 | Romania |
| Investigational Site Number 703402 | Bratislava | 85101 | Slovakia |
| Investigational Site Number 703403 | Košice | 04001 | Slovakia |
| Investigational Site Number 703406 | Košice | 04013 | Slovakia |
| Investigational Site Number 703404 | Moldava nad Bodvou | 04525 | Slovakia |
| Investigational Site Number 703405 | Nitra | 94911 | Slovakia |
| Investigational Site Number 703401 | Žilina | 01001 | Slovakia |
| Investigational Site Number 752402 | Skellefteå | 931 32 | Sweden |
| Investigational Site Number 752401 | Stockholm | 171 76 | Sweden |
| Investigational Site Number 752403 | Vaxjo | 351 85 | Sweden |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Insulin Glargine/Lixisenatide Fixed Ratio Combination | FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted. |
| BG001 | Insulin Glargine | Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Gender | Count of Participants | Participants |
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| Race | Number | participants |
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| Ethnicity | Number | participants |
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| Screening HbA1c | Mean | Standard Deviation | percentage of haemoglobin |
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| Baseline BMI | Mean | Standard Deviation | kg/m^2 |
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| Duration of Diabetes | Mean | Standard Deviation | years |
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| Daily Dose of Metformin | Mean | Standard Deviation | mg |
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| Fasting Plasma Glucose (FPG) | Mean | Standard Deviation | mmol/L |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change in HbA1c From Baseline to Week 24 | Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of investigational medicinal product (IMP). | Modified intent-to-treat (mITT) population consisted of all randomized participants received at least 1 dose of IMP and had both baseline and at least 1 post-baseline efficacy assessment. Number of participants analyzed = participants with both baseline and at least one post-baseline HbA1c assessment during on-treatment period. | Posted | Least Squares Mean | Standard Error | percentage of hemoglobin | Baseline, Week 24 |
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| Secondary | Change in 2-hour Postprandial Plasma Glucose (PPG) From Baseline to Week 24 | The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | mITT population.Here, number of participants analyzed = participants with both baseline and at least one post-baseline 2-hour PPG assessment during on-treatment period. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Week 24 |
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| Secondary | Change in 2-hour Plasma Glucose Excursion From Baseline to Week 24 | 2-hour plasma glucose excursion = 2-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | mITT population. Here, number of participants analyzed = participants with both baseline and at least one post-baseline plasma glucose excursion assessment during on-treatment period. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Week 24 |
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| Secondary | Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profiles From Baseline to Week 24 | Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, over a single day, once in a week before baseline, before visit Week 12 and before visit Week 24 and the average value across the profiles performed in the week before a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline 7-point SMPG assessment during on-treatment period. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Week 24 |
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| Secondary | Change in Body Weight From Baseline to Week 24 | Change in body weight was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 3 days after the last injection of IMP. | mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during on-treatment period. | Posted | Least Squares Mean | Standard Error | kg | Baseline, Week 24 |
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| Secondary | Average Daily Insulin Glargine Dose at Week 24 | Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | mITT population. Here, number of participants analyzed = participants with insulin glargine dose measured during on-treatment period | Posted | Least Squares Mean | Standard Error | Units (U) | Week 24 |
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| Secondary | Change in FPG From Baseline to Week 24 | Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 1 day after the last injection of IMP. | mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline FPG assessment during on-treatment period. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Week 24 |
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| Secondary | Percentage of Participants Requiring Rescue Therapy During 24-week Treatment Period | Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceed the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) were performed. Threshold values from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8%. | mITT population. | Posted | Number | percentage of participants | Baseline up to Week 24 |
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| Secondary | Percentage of Participants With HbA1c ≤6.5 % or <7.0 % at Week 24 | On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP. | mITT population. Here, number of participants analyzed = participants with at least one post-baseline HbA1c assessment during on-treatment period. | Posted | Number | percentage of participants | Week 24 |
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| Secondary | Change in 30-minute and 1-hour PPG From Baseline to Week 24 | The 30 minute and 1-hour PPG test measured blood glucose 30 minutes and 1-hour after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline PPG assessment during on-treatment period. Here, 'n' signifies number of participants with available data for specified category. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Week 24 |
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| Secondary | Change in 30 Minute and 1-hour Plasma Glucose Excursion From Baseline to Week 24 | 30-minute and 1-hour plasma glucose excursion = 30-minute and 1-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP. | mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline plasma glucose excursion assessment during on-treatment period. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Week 24 |
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| Secondary | Percentage of Participants Reaching HbA1c <7% at Week 24 With no Documented Symptomatic Hypoglycemia During 24-week Treatment Period | Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L). Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one documented symptomatic hypoglycemia before the introduction of rescue medication and up to 1 day after the last injection of IMP. Otherwise, they were counted as missing data. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP. | mITT population. Here, number of participants analyzed = participants with at least one post-baseline HbA1c assessment during on-treatment period. | Posted | Number | percentage of participants | Baseline up to Week 24 |
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| Secondary | Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 | Participants without any post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (for HbA1c and body weight) was available and showed non-response. Otherwise, they were counted as missing data. | mITT population. Here, number of participants analyzed = participants with any post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart or with one of the components (for HbA1c and body weight) showing non-response based on the last post-baseline on-treatment value. | Posted | Number | percentage of participants | Week 24 |
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| Secondary | Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia | Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes were associated with sufficient neuroglycopenia to induce seizure, unconsciousness or coma. All episodes in which neurological impairment was severe enough to prevent self-treatment and which were thought to place participants at risk for injury to themselves or others. | Safety population that included all randomized participants who received at least 1 dose of study medication regardless of the amount of treatment administered. | Posted | Number | percentage of participants | First dose of study drug up to 3 days after the last dose administration (maximum of 219 days) |
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All Adverse events (AEs) were collected from signature of the informed consent from up to the final visit (Week 24) regardless of seriousness or relationship to investigational product.
Reported adverse events are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first injection of open-label IMP up to 3 days after the last injection of IMP, regardless of the introduction of rescue therapy).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Insulin Glargine/Lixisenatide Fixed Ratio Combination | FRC injected subcutaneously QD for 24 weeks. Dose individually adjusted (median exposure: 169 days). | 9 | 161 | 26 | 161 | ||
| EG001 | Insulin Glargine | Insulin glargine injected subcutaneously QD for 24 weeks. Dose individually adjusted (median exposure: 169 days). | 6 | 162 | 21 | 162 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
| |
| Ovarian cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Diabetic neuropathy | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Calculus ureteric | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
| |
| ECG signs of myocardial ischaemia | Investigations | MedDRA 15.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | Contact-US@sanofi.com |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069036 | Insulin Glargine |
| C479460 | lixisenatide |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D049528 | Insulin, Long-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Male |
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| Black |
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| Asian/Oriental |
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| Non Hispanic |
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The non-inferiority of insulin glargine/lixisenatide FRC versus insulin glargine was tested first, at alpha level of 0.025 (1-sided) and a non-inferiority margin of 0.4% HbA1c. If non-inferiority was established, then a test of superiority of insulin glargine/lixisenatide FRC over insulin glargine would be performed, at alpha level of 0.05 (2-sided). The non-inferiority was assessed using upper bound of 2-sided 95% confidence interval (CI) at ≤0.4%. |
| Analysis was performed using ANCOVA model with treatment groups, randomization strata of screening HbA1c (<8.0, ≥8.0%), randomization strata of screening BMI (<30 kg/m^2, ≥30 kg/m^2), and country as fixed effects and baseline HbA1c value as covariates. If non-inferiority was established, then a test of superiority of insulin glargine/lixisenatide FRC over insulin glargine would be performed, at alpha level of 0.05 (2-sided). | ANCOVA | 0.0130 | Threshold for significance at 0.05 level. | LS Mean Difference | -0.17 | Standard Error of the Mean | 0.070 | 2-Sided | 95 | -0.312 | -0.037 | Insulin glargine/Lixisenatide FRC vs Insulin glargine | No | Superiority or Other |
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