Type 2 Diabetes
Conditions
Brief summary
Primary objective: \- To evaluate the effect of lixisenatide versus placebo over a period of 24 weeks on glycemic control, as evaluated by glycosylated hemoglobin (HbA1c) reduction, in older type 2 diabetes participants (T2DM) who are inadequately controlled with their current anti-diabetic treatment regimen. Main secondary objective: \- To assess the safety and tolerability of lixisenatide compared to placebo in older T2DM participants (including occurrence of documented (Plasma Glucose PG \< 60 mg/dL) symptomatic hypoglycemia and gastrointestinal side effects). Other secondary objectives: * To assess the effect of lixisenatide compared to placebo after 24-week treatment on: * Fasting plasma glucose (FPG); * During liquid standardized breakfast meal challenge test : 2 hour- Postprandial Plasma Glucose (PPG) and Plasma Glucose Excursion; * 7-point Self-monitored plasma glucose (SMPG) profile; * Body weight; * Change in total daily dose of basal insulin (if taken); * Percentage of participants requiring rescue therapy * Safety and tolerability; * To assess lixisenatide pharmacokinetic profile; * To assess anti-lixisenatide antibody development.
Detailed description
Approximately 31 weeks including 24 week treatment period.
Interventions
DRUGLixisenatide (AVE0010)
Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning Route of administration: Subcutaneous injection
DRUGPlacebo
Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning Route of administration: Subcutaneous injection
DRUGAntidiabetic background therapy
Participants received a stable regimen of anti-diabetic background therapy for at least 3 months prior to screening, during the placebo run-in period and the 24 week treatment period. Allowed background antidiabetic therapy included metformin, sulfonylurea (except glibenclamide \>10 mg, gliclazide \>160 mg), meglitinides (except repaglinide \>6 mg), pioglitazone and basal insulin. Insulin glargine, neutral protamine hagedorn (NPH) insulin, detemir, lente and ultralente were considered as basal insulin.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Older participants, aged 70 years and above, with T2DM inadequately controlled on their current anti-diabetic pharmaceutical treatment regimen. * Signed written informed consent.
Exclusion criteria
* At screening HbA1c ≤7.0% or \>10% (Acknowledging that the threshold of 7% may not be appropriate for all older participants and that this was the responsibility of the investigator to include the participant based on an individual evaluation of the expected benefits of better glycemic control versus risk of hypoglycemia). * At screening participants on both basal insulin and sulfonylurea or basal insulin and meglitinides. * At screening FPG \>250 mg/dL (\>13.9 mmol/L). * Type 1 diabetes mellitus or history of ketoacidosis within one year prior to the screening visit. * Type 2 diabetes mellitus diagnosed less than 1 year prior to screening. * Anti-diabetic treatment not at a stable regimen or initiated within the last 3 months prior to screening. * Treatment within the 3 months preceding the screening with other anti-diabetic agent than allowed background therapy. Allowed therapy includes metformin, sulfonylurea (except glibenclamide \>10mg, gliclazide \>160mg), meglitinides (except repaglinide \>6mg), pioglitazone and basal insulin and should follow local product circulars and labeling restrictions for the study population. * Participants who had been on an approved or an investigational Glucagon-like peptide 1 (GLP-1) medication (exenatide, liraglutide, lixisenatide or others). * History of severe hypoglycemia associated with symptoms unawareness or results in unconsciousness/coma/seizure in the 6 months prior to screening. * BMI \<22 or \>40 kg/m\^2. * Malnutrition assessed clinically by the investigator or any sub-investigator and by Mini-Nutritional Assessment-Short Form (MNA-SF) score \<12 in countries (the judgment of the investigator prevails on questionnaires scores). * Cognitive disorder and dementia assessed clinically by the investigator or any sub investigator and by Mini Mental State Examination (MMSE) score \<24 (the judgment of the investigator prevails on questionnaires scores), or any neurologic disorder that affected the participant's ability to participate in the study. * Participant who had a glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease (MDRD) formula \<30ml/min/1.73m\^2). * Participant with severe or uncontrolled disease, or any clinically significant abnormality identified on physical examination or investigational clinical procedure that, in the judgment of the investigator or any sub-investigator, would preclude safe completion of the study or constrains efficacy assessment. * Laboratory findings at the time of screening: * Amylase and/or lipase: \>3 times the upper limit of the normal (ULN) laboratory range * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times ULN * Calcitonin \>20 pg/mL (5.9 pmol/L). * Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (i.e. worsening) and not controlled (i.e. prolonged nausea and vomiting) gastroesophageal reflux disease within 6 months prior to screening. * History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease. * Personal or immediate family history of medullary thyroid cancer or genetic conditions that predisposed to medullary thyroid cancer (e.g., multiple endocrine neoplasia syndromes). The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in HbA1c From Baseline to Week 24 | Baseline, Week 24 | Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed=participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average 7-point SMPG Profiles From Baseline to Week 24 | Baseline, Week 24 | Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week 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. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug. |
| Change in Body Weight From Baseline to Week 24 | Baseline, 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 up to 3 days after the last dose of study drug. |
| Change in FPG From Baseline to Week 24 | Baseline, Week 24 | Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug. |
| Percentage of Participants Requiring Rescue Therapy During 24 Week Treatment Period | Baseline up to Week 24 | 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 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 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 \>9%. |
| Change in 2-Hour PPG From Baseline to Week 24 | Baseline, Week 24 | The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. |
| Change in Total Daily Basal Insulin Dose From Baseline to Week 24 (in Participants Who Took Basal Insulin as Background Therapy) | Baseline, Week 24 | Change in basal insulin dose was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. |
| Percentage of Participants With Symptomatic and Severe Symptomatic Hypoglycemia | First dose of study drug up to 3 days after the last dose administration (maximum of 171 days) | 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 participant 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. |
| Percentage of Participants With HbA1c Reduction >0.5% at Week 24 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia | Week 24 | The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. |
| Percentage of Participants With Gastrointestinal Disorders | Up to Day 171 | — |
| Change in Plasma Glucose Excursions From Baseline to Week 24 | Baseline, Week 24 | Plasma glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the liquid standardized breakfast meal test, before study drug administration. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. |
Countries
Australia, Bulgaria, Canada, Denmark, Germany, Norway, Peru, Poland, South Africa, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 83 centers in 13 countries. A total of 786 participants were screened between June 10, 2013 and July 09, 2014.
Pre-assignment details
A total of 426 participants underwent 4 week placebo run-in period. 436 participants were screen failures and 76 were run-in failures; the most frequent reason for screen and run-in failure was glycosylated hemoglobin (HbA1c) criteria not met at end of the run-in phase. A total of 350 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Lixisenatide Lixisenatide 10 mcg subcutaneously QD for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to Week 24. If the maintenance dose of 20 mcg was not tolerated, dose could be reduced to 10 mcg. | 176 |
| Placebo Placebo (matched to lixisenatide) subcutaneously QD for 24 Weeks. | 174 |
| Total | 350 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 10 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Other than specified above | 5 | 9 |
| Overall Study | Poor compliance to protocol | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Lixisenatide | Total |
|---|---|---|---|
| 2-Hour Postprandial Plasma Glucose (PPG) | 14.87 mmol/L STANDARD_DEVIATION 3.69 | 15.18 mmol/L STANDARD_DEVIATION 3.78 | 15.03 mmol/L STANDARD_DEVIATION 3.74 |
| 7-Point Self-monitored Plasma Glucose (SMPG) | 9.97 mmol/L STANDARD_DEVIATION 1.98 | 9.79 mmol/L STANDARD_DEVIATION 2.02 | 9.87 mmol/L STANDARD_DEVIATION 2 |
| Age, Continuous | 74.4 years STANDARD_DEVIATION 3.8 | 74 years STANDARD_DEVIATION 4 | 74.2 years STANDARD_DEVIATION 3.9 |
| Body Mass Index (BMI) | 30.09 kg/m^2 STANDARD_DEVIATION 4.53 | 29.91 kg/m^2 STANDARD_DEVIATION 3.7 | 30.00 kg/m^2 STANDARD_DEVIATION 4.13 |
| Body Weight | 80.08 kg STANDARD_DEVIATION 16.76 | 80.81 kg STANDARD_DEVIATION 14.54 | 80.45 kg STANDARD_DEVIATION 15.66 |
| Duration of Diabetes | 14.63 years STANDARD_DEVIATION 7.87 | 13.63 years STANDARD_DEVIATION 7.34 | 14.13 years STANDARD_DEVIATION 7.62 |
| Ethnicity Hispanic | 48 participants | 51 participants | 99 participants |
| Ethnicity Not Hispanic | 126 participants | 125 participants | 251 participants |
| Fasting Plasma Glucose (FPG) | 8.89 mmol/L STANDARD_DEVIATION 2.26 | 8.83 mmol/L STANDARD_DEVIATION 2.38 | 8.86 mmol/L STANDARD_DEVIATION 2.32 |
| Glucose Excursion | 6.02 mmol/L STANDARD_DEVIATION 3.17 | 6.51 mmol/L STANDARD_DEVIATION 3.15 | 6.26 mmol/L STANDARD_DEVIATION 3.16 |
| HbA1c | 8.05 Percentage of HbA1c STANDARD_DEVIATION 0.69 | 8.04 Percentage of HbA1c STANDARD_DEVIATION 0.72 | 8.04 Percentage of HbA1c STANDARD_DEVIATION 0.71 |
| Number of Participants with Categorical BMI <30 kg/m^2 | 96 participants | 102 participants | 198 participants |
| Number of Participants with Categorical BMI ≥30 kg/m^2 | 78 participants | 74 participants | 152 participants |
| Race Asian/Oriental | 11 participants | 5 participants | 16 participants |
| Race Black | 0 participants | 3 participants | 3 participants |
| Race Caucasian/white | 122 participants | 128 participants | 250 participants |
| Race Other | 41 participants | 40 participants | 81 participants |
| Sex: Female, Male Female | 84 Participants | 84 Participants | 168 Participants |
| Sex: Female, Male Male | 90 Participants | 92 Participants | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 89 / 176 | 58 / 174 |
| serious Total, serious adverse events | 8 / 176 | 10 / 174 |
Outcome results
Primary
Absolute 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 on-treatment observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed=participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.
Time frame: Baseline, Week 24
Population: Modified intent to treat (mITT) population: all randomized participants who received at least one dose of study drug; and had both baseline and at least one post-baseline efficacy assessment, irrespective of compliance with study protocol/procedures.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Absolute Change in HbA1c From Baseline to Week 24 | -0.57 percentage of hemoglobin | Standard Error 0.075 |
| Placebo | Absolute Change in HbA1c From Baseline to Week 24 | 0.06 percentage of hemoglobin | Standard Error 0.072 |
Comparison: Analysis was performed using analysis of covariance (ANCOVA) model with treatment groups, randomization strata of Week -1 HbA1c (\<8.0, ≥8.0%), randomization strata of basal insulin use at screening, randomization strata of Week -1 glomerular filtration rate (eGFR) (≥30 to \<60, ≥60 ml/min/1.73 m\^2), and country as fixed effects and baseline HbA1c value as a covariate.p-value: <0.000195% CI: [-0.81, -0.464]ANCOVA
Secondary
Change in 2-Hour PPG From Baseline to Week 24
The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
Time frame: Baseline, Week 24
Population: mITT population. Here, number of participants analyzed=participants with baseline and at least one post-baseline 2-hour PPG assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Change in 2-Hour PPG From Baseline to Week 24 | -5.12 mmol/L | Standard Error 0.392 |
| Placebo | Change in 2-Hour PPG From Baseline to Week 24 | -0.07 mmol/L | Standard Error 0.393 |
Comparison: Analysis was performed using ANCOVA model with treatment groups, randomization strata of Week -1 HbA1c (\<8.0, ≥8.0%), randomization strata of basal insulin use at screening, randomization strata of Week -1 eGFR (≥30 to \<60, ≥60 ml/min/1.73 m\^2), and country as fixed effects and baseline 2-hour PPG value as a covariate. Hierarchical testing procedure was used to control type I error at 0.05. Testing was then performed sequentially in the order the endpoints were reported.p-value: <0.000195% CI: [-5.96, -4.132]ANCOVA
Secondary
Change in Average 7-point 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 three times in a week before baseline, before visit Week 12 and before visit week 26 and the average value across the profiles performed in the week 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. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug.
Time frame: Baseline, Week 24
Population: mITT population. Here, number of participants analyzed=participants with baseline and at least one post-baseline 7-point SMPG assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Change in Average 7-point SMPG Profiles From Baseline to Week 24 | -1.15 mmol/L | Standard Error 0.186 |
| Placebo | Change in Average 7-point SMPG Profiles From Baseline to Week 24 | -0.19 mmol/L | Standard Error 0.189 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with treatment groups, randomization strata of Week -1 HbA1c (\<8.0, ≥8.0%), randomization strata of basal insulin use at screening, randomization strata of Week -1 eGFR (≥30 to \<60, ≥60 ml/min/1.73 m\^2), and country as fixed effects and baseline 7-point SMPG value as a covariate.p-value: <0.000195% CI: [-1.39, -0.527]ANCOVA
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 up to 3 days after the last dose of study drug.
Time frame: Baseline, Week 24
Population: mITT population. Here, number of participants analyzed=participants with baseline and at least one post-baseline body weight assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Change in Body Weight From Baseline to Week 24 | -1.47 kg | Standard Error 0.241 |
| Placebo | Change in Body Weight From Baseline to Week 24 | -0.16 kg | Standard Error 0.228 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with treatment groups, randomization strata of Week -1 HbA1c (\<8.0, ≥8.0%), randomization strata of basal insulin use at screening, randomization strata of Week -1 eGFR (≥30 to \<60, ≥60 ml/min/1.73 m\^2), and country as fixed effects and baseline body weight value as a covariate.p-value: <0.000195% CI: [-1.862, -0.769]ANCOVA
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. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug.
Time frame: Baseline, Week 24
Population: mITT population. Here, number of participants analyzed=participants with baseline and at least one post-baseline FPG assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Change in FPG From Baseline to Week 24 | -0.3 mmol/L | Standard Error 0.224 |
| Placebo | Change in FPG From Baseline to Week 24 | 0.01 mmol/L | Standard Error 0.218 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using ANCOVA model with treatment groups, randomization strata of Week -1 HbA1c (\<8.0, ≥8.0%), randomization strata of basal insulin use at screening, randomization strata of Week -1 eGFR (≥30 to \<60, ≥60 ml/min/1.73 m\^2), and country as fixed effects and baseline FPG value as a covariate.p-value: 0.234795% CI: [-0.828, 0.204]ANCOVA
Secondary
Change in Plasma Glucose Excursions From Baseline to Week 24
Plasma glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the liquid standardized breakfast meal test, before study drug administration. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
Time frame: Baseline, Week 24
Population: mITT population. Here, number of participants=participants with baseline and at least one post-baseline plasma glucose excursion assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Change in Plasma Glucose Excursions From Baseline to Week 24 | -4.71 mmol/L | Standard Error 0.331 |
| Placebo | Change in Plasma Glucose Excursions From Baseline to Week 24 | -0.25 mmol/L | Standard Error 0.331 |
Secondary
Change in Total Daily Basal Insulin Dose From Baseline to Week 24 (in Participants Who Took Basal Insulin as Background Therapy)
Change in basal insulin dose was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug.
Time frame: Baseline, Week 24
Population: mITT population. Here, number of participants analyzed=participants with baseline and at least one post-baseline basal insulin dose assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Change in Total Daily Basal Insulin Dose From Baseline to Week 24 (in Participants Who Took Basal Insulin as Background Therapy) | -2.97 units | Standard Error 1.145 |
| Placebo | Change in Total Daily Basal Insulin Dose From Baseline to Week 24 (in Participants Who Took Basal Insulin as Background Therapy) | -1.3 units | Standard Error 1.076 |
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 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 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 \>9%.
Time frame: Baseline up to Week 24
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lixisenatide | Percentage of Participants Requiring Rescue Therapy During 24 Week Treatment Period | 2.9 percentage of participants |
| Placebo | Percentage of Participants Requiring Rescue Therapy During 24 Week Treatment Period | 10.4 percentage of participants |
Secondary
Percentage of Participants With Gastrointestinal Disorders
Time frame: Up to Day 171
Population: Analysis was performed on safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lixisenatide | Percentage of Participants With Gastrointestinal Disorders | 40.3 percentage of participants |
| Placebo | Percentage of Participants With Gastrointestinal Disorders | 20.7 percentage of participants |
Secondary
Percentage of Participants With HbA1c Reduction >0.5% at Week 24 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia
The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug.
Time frame: Week 24
Population: mITT population. Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one symptomatic hypoglycemia. Otherwise, they were counted as missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lixisenatide | Percentage of Participants With HbA1c Reduction >0.5% at Week 24 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia | 57.6 percentage of participants |
| Placebo | Percentage of Participants With HbA1c Reduction >0.5% at Week 24 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia | 21.5 percentage of participants |
Secondary
Percentage of Participants With Symptomatic 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 participant 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 (maximum of 171 days)
Population: Analysis was performed on safety population defined as all randomized participants who received any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lixisenatide | Percentage of Participants With Symptomatic and Severe Symptomatic Hypoglycemia | Symptomatic hypoglycemia | 7.4 percentage of participants |
| Lixisenatide | Percentage of Participants With Symptomatic and Severe Symptomatic Hypoglycemia | Severe symptomatic hypoglycemia | 0.57 percentage of participants |
| Placebo | Percentage of Participants With Symptomatic and Severe Symptomatic Hypoglycemia | Symptomatic hypoglycemia | 5.7 percentage of participants |
| Placebo | Percentage of Participants With Symptomatic and Severe Symptomatic Hypoglycemia | Severe symptomatic hypoglycemia | 0 percentage of participants |