Diabetes Mellitus, Type 2
Conditions
Keywords
hyperglycemia, GLP-1
Brief summary
The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, used in a 2-step dose titration regimen in monotherapy, over a period of 12 weeks of treatment. The primary objective is to assess the effects of lixisenatide, in comparison to placebo, on glycemic control using a 2-step dose titration regimen in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 12. Secondary objectives are to assess the effects of lixisenatide, in comparison to placebo, on glycemic control in terms of HbA1c reduction when it is used in a one-step dose titration regimen over a period of 12 weeks, body weight, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) after a standardized meal, to assess the safety and tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.
Detailed description
This is a double-blind, randomized, placebo-controlled, 4-arm, unbalanced design, parallel group study with a two-step titration regimen or a one-step titration regimen. The study is double-blind with regard to active and placebo treatments; however neither the study drug volume nor the titration regimens (that is, two-step or one-step) are blinded.
Interventions
DRUGLixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
DRUGPlacebo
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
DEVICEPen auto-injector
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus, diagnosed for at least 2 months at the time of the screening visit, not treated with any antidiabetic agent
Exclusion criteria
* HbA1c less than (\<) 7 percent (%) or greater than (\>) 10% * At the time of screening age \< legal age of majority * Pregnant or breastfeeding women and women of childbearing potential without effective contraceptive method of birth control * Type 1 diabetes mellitus * Type 2 diabetes treated by an antidiabetic agent within the 3 months preceding the study * Fasting plasma glucose 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 previous 3 months * History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease * History of metabolic acidosis, including diabetic ketoacidosis within the previous year * Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within the previous 3 months * History of myocardial infarction, stroke, or heart failure requiring hospitalization within the previous 6 months * Known history of drug or alcohol abuse within the previous 6 months * 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 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, alanine aminotransferase or alkaline phosphatase: \>2 times the upper limit of the normal (ULN) laboratory range; amylase and/or lipase: \>3 ULN; total bilirubin: \>1.5 ULN (except in case of Gilbert's syndrome); hemoglobin \<11 gram/deciliter (g/dL) and/or neutrophils \<1,500 per cubic mm (mm\^3) and/or platelets \<100,000/mm\^3; positive test for Hepatitis B surface antigen and/or hepatitis C antibody * Any clinically significant abnormality identified by physical examination, laboratory tests, electrocardiogram or vital sign at the time of screening that in the judgment of the investigator or any sub investigator precludes safe completion of the study or hinders the efficacy assessment * Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason * Use of systemic glucocorticoids (excluding topical application or inhaled forms) within the previous 3 months * Participation in any previous study with lixisenatide * Use of any investigational drug within 3 months prior to study * End-stage renal disease as defined by a calculated serum creatinine clearance of \<15 milliliter/minute and/or patients on dialysis * 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 the previous 6 months * History of allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past or to metacresol * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 | Baseline, Week 12 | Absolute change = HbA1c value at Week 12 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 assessment for at least 1 efficacy variable, were required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | Baseline, Week 12 | Change was calculated by subtracting baseline value from Week 12 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 assessment for at least 1 efficacy variable, were required. |
| Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12 | Week 12 | 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 assessment for at least 1 efficacy variable, were required. |
| Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12 | Week 12 | 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 assessment for at least 1 efficacy variable, were required. |
| Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period | Baseline up to Week 12 | Routine fasting self monitored plasma glucose (SMPG) and central laboratory FPG 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 was performed. Threshold values for fasting SMPG/FPG: from baseline to Week 8: \>270 milligram/deciliter (mg/dL) (15 mmol/L) and from Week 8 to Week 12: \>240 mg/dL (13.3 mmol/L). 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. |
| Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12 | Baseline, Week 12 | The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal (performed in selected sites). Change was calculated by subtracting baseline value from Week 12 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. 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. |
| Change From Baseline in Body Weight at Week 12 | Baseline, Week 12 | Change was calculated by subtracting baseline value from Week 12 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 assessment for at least 1 efficacy variable, were required. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | First dose of study drug up to 3 days after the last dose administration | 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. |
| Change From Baseline in Glucose Excursion at Week 12 | Baseline, Week 12 | Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test (performed in selected sites), before study drug administration. Change was calculated by subtracting baseline value from Week 12 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. 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. |
| Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12 | Baseline, Week 12 | 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 assessment for at least 1 efficacy variable, were required. |
Countries
Belgium, India, Israel, Japan, Mexico, Poland, Romania, Russia, South Korea, Tunisia, Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 61 centers (68 were initiated) in 12 countries between May 14, 2008 and December 14, 2009.
Pre-assignment details
A total of 795 patients were screened of which 434 (54.6%) 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 361 patients were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Combined) Included all patients who received 2-step initiation regimen of volume matching placebo and 1-step initiation regimen of volume matching placebo. | 122 |
| 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 Week 12. | 120 |
| Lixisenatide (One-Step Titration) 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to Week 12. | 119 |
| Total | 361 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 5 | 3 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Overall Study | Poor compliance to protocol | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 4 | 8 |
Baseline characteristics
| Characteristic | Total | Placebo (Combined) | Lixisenatide (Two-Step Titration) | Lixisenatide (One-Step Titration) |
|---|---|---|---|---|
| 2-Hour Postprandial Plasma Glucose (PPG) | 14.57 mmol/L STANDARD_DEVIATION 4.05 | 14.27 mmol/L STANDARD_DEVIATION 4.84 | 14.81 mmol/L STANDARD_DEVIATION 3.87 | 14.62 mmol/L STANDARD_DEVIATION 3.41 |
| Age, Continuous | 53.7 years STANDARD_DEVIATION 10.5 | 54.1 years STANDARD_DEVIATION 11 | 53.3 years STANDARD_DEVIATION 9.7 | 53.8 years STANDARD_DEVIATION 10.9 |
| Body Mass Index (BMI) | 31.91 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.66 | 31.76 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.69 | 32.34 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.72 | 31.65 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.62 |
| Body Weight | 87.20 kilogram (kg) STANDARD_DEVIATION 21.78 | 86.08 kilogram (kg) STANDARD_DEVIATION 22.21 | 89.04 kilogram (kg) STANDARD_DEVIATION 22.16 | 86.50 kilogram (kg) STANDARD_DEVIATION 21 |
| Duration of Diabetes | 1.33 years | 1.37 years | 1.42 years | 1.11 years |
| Fasting Plasma Glucose (FPG) | 9.03 millimole per liter (mmol/L) STANDARD_DEVIATION 2.04 | 8.90 millimole per liter (mmol/L) STANDARD_DEVIATION 2.16 | 9.15 millimole per liter (mmol/L) STANDARD_DEVIATION 1.99 | 9.04 millimole per liter (mmol/L) STANDARD_DEVIATION 1.97 |
| Glucose Excursion | 5.27 mmol/L STANDARD_DEVIATION 3.25 | 4.82 mmol/L STANDARD_DEVIATION 3.69 | 5.67 mmol/L STANDARD_DEVIATION 3.05 | 5.34 mmol/L STANDARD_DEVIATION 2.96 |
| Glycosylated Hemoglobin (HbA1c) | 8.04 percentage of hemoglobin STANDARD_DEVIATION 0.9 | 8.07 percentage of hemoglobin STANDARD_DEVIATION 0.91 | 7.98 percentage of hemoglobin STANDARD_DEVIATION 0.92 | 8.07 percentage of hemoglobin STANDARD_DEVIATION 0.87 |
| Race/Ethnicity, Customized Ethnicity: Hispanic | 78 participants | 31 participants | 25 participants | 22 participants |
| Race/Ethnicity, Customized Ethnicity: Non Hispanic | 283 participants | 91 participants | 95 participants | 97 participants |
| Race/Ethnicity, Customized Race: Asian/Oriental | 80 participants | 24 participants | 27 participants | 29 participants |
| Race/Ethnicity, Customized Race: Black | 6 participants | 3 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Race: Caucasian/White | 263 participants | 90 participants | 88 participants | 85 participants |
| Race/Ethnicity, Customized Race: Other | 12 participants | 5 participants | 5 participants | 2 participants |
| Sex: Female, Male Female | 175 Participants | 62 Participants | 57 Participants | 56 Participants |
| Sex: Female, Male Male | 186 Participants | 60 Participants | 63 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 61 | 8 / 61 | 19 / 122 | 35 / 120 | 31 / 119 | 66 / 239 |
| serious Total, serious adverse events | 3 / 61 | 2 / 61 | 5 / 122 | 1 / 120 | 0 / 119 | 1 / 239 |
Outcome results
Primary
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
Absolute change = HbA1c value at Week 12 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 assessment for at least 1 efficacy variable, were required.
Time frame: Baseline, Week 12
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 | -0.19 percentage of hemoglobin | Standard Error 0.121 |
| Lixisenatide (Two-Step Titration) | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 | -0.73 percentage of hemoglobin | Standard Error 0.116 |
| Lixisenatide (One-Step Titration) | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 | -0.85 percentage of hemoglobin | Standard Error 0.119 |
Comparison: To detect a difference of 0.5% in change in HbA1c at Week 12 between 1 lixisenatide arm and placebo (combined), 120 patients per group would provide a power of 90% assuming common standard deviation of 1.2% with 2-sided test at 5% significance level.~Statistical testing: 2-sided at significance level=0.05. Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (\<8.0,\>=8.0%), BMI (\<30,\>=30 kg/m\^2), country as fixed effects, baseline HbA1c as covariate.p-value: <0.000195% CI: [-0.785, -0.3]ANCOVA
Comparison: To detect a difference of 0.5% in change in HbA1c at Week 12 between 1 lixisenatide arm and placebo (combined), 120 patients per group would provide a power of 90% assuming common standard deviation of 1.2% with 2-sided test at 5% significance level.~Statistical testing: 2-sided at significance level=0.05. Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (\<8.0,\>=8.0%), BMI (\<30,\>=30 kg/m\^2), country as fixed effects, baseline HbA1c as covariate.p-value: <0.000195% CI: [-0.903, -0.423]ANCOVA
Secondary
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12
The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal (performed in selected sites). Change was calculated by subtracting baseline value from Week 12 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. 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.
Time frame: Baseline, Week 12
Population: Subgroup for standardized meal test. Missing data was imputed using last observation carried forward (LOCF). Here, number of patients analyzed = patients with baseline and at least 1 post-baseline 2-hour PPG assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12 | -0.65 mmol/L | Standard Error 0.563 |
| Lixisenatide (Two-Step Titration) | Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12 | -4.51 mmol/L | Standard Error 0.572 |
| Lixisenatide (One-Step Titration) | Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 12 | -5.47 mmol/L | Standard Error 0.549 |
Secondary
Change From Baseline in Body Weight at Week 12
Change was calculated by subtracting baseline value from Week 12 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 assessment for at least 1 efficacy variable, were required.
Time frame: Baseline, Week 12
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Body Weight at Week 12 | -1.98 kilogram | Standard Error 0.341 |
| Lixisenatide (Two-Step Titration) | Change From Baseline in Body Weight at Week 12 | -1.96 kilogram | Standard Error 0.326 |
| Lixisenatide (One-Step Titration) | Change From Baseline in Body Weight at Week 12 | -1.92 kilogram | Standard Error 0.338 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
Change was calculated by subtracting baseline value from Week 12 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 assessment for at least 1 efficacy variable, were required.
Time frame: Baseline, Week 12
Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline FPG assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | 0.19 mmol/L | Standard Error 0.255 |
| Lixisenatide (Two-Step Titration) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | -0.68 mmol/L | Standard Error 0.247 |
| Lixisenatide (One-Step Titration) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | -0.89 mmol/L | Standard Error 0.254 |
Secondary
Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period
Routine fasting self monitored plasma glucose (SMPG) and central laboratory FPG 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 was performed. Threshold values for fasting SMPG/FPG: from baseline to Week 8: \>270 milligram/deciliter (mg/dL) (15 mmol/L) and from Week 8 to Week 12: \>240 mg/dL (13.3 mmol/L). 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.
Time frame: Baseline up to Week 12
Population: mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period | 2.5 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period | 1.7 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients Requiring Rescue Therapy During the Double-Blind Treatment Period | 0.8 percentage of participants |
Secondary
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12
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 assessment for at least 1 efficacy variable, were required.
Time frame: Week 12
Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12 | 26.8 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12 | 52.2 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 12 | 46.5 percentage of participants |
Secondary
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12
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 assessment for at least 1 efficacy variable, were required.
Time frame: Week 12
Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12 | 12.5 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12 | 31.9 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 12 | 25.4 percentage of participants |
Other Pre-specified
Change From Baseline in Glucose Excursion at Week 12
Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test (performed in selected sites), before study drug administration. Change was calculated by subtracting baseline value from Week 12 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. 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.
Time frame: Baseline, Week 12
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Glucose Excursion at Week 12 | -0.67 mmol/L | Standard Error 0.447 |
| Lixisenatide (Two-Step Titration) | Change From Baseline in Glucose Excursion at Week 12 | -3.77 mmol/L | Standard Error 0.454 |
| Lixisenatide (One-Step Titration) | Change From Baseline in Glucose Excursion at Week 12 | -4.36 mmol/L | Standard Error 0.436 |
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.
Time frame: First dose of study drug up to 3 days after the last dose administration
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Combined) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic hypoglycemia | 2 participants |
| Placebo (Combined) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe symptomatic hypoglycemia | 0 participants |
| Lixisenatide (Two-Step Titration) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic hypoglycemia | 3 participants |
| Lixisenatide (Two-Step Titration) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe symptomatic hypoglycemia | 0 participants |
| Lixisenatide (One-Step Titration) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic hypoglycemia | 1 participants |
| Lixisenatide (One-Step Titration) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe symptomatic hypoglycemia | 0 participants |
Other Pre-specified
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12
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 assessment for at least 1 efficacy variable, were required.
Time frame: Baseline, Week 12
Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12 | 17.2 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12 | 16.2 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 12 | 18.3 percentage of participants |