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, as an add-on treatment to metformin, over a period of 24 weeks of treatment, followed by an extension. The primary objective is to assess the effects of lixisenatide when added to metformin on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction when it is used in two steps dose titration regimen at Week 24. Secondary objectives are to assess the effects of lixisenatide when added to metformin on glycemic control in comparison to placebo in terms of HbA1c reduction when it is used in a one-step dose titration regimen, the percentage of patients with HbA1c less than 7 percent or less than or equal to 6.5%, body weight, fasting plasma glucose (FPG); to assess the safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.
Detailed description
Patients who complete the 24-week main double-blind treatment would undergo a variable double-blind extension treatment, which ends for all patients at approximately the scheduled date of Week 76 visit (Visit 25) for the last randomized patients.
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
DRUGMetformin
Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/day for at least 3 months prior to screening visit
Exclusion criteria
* HbA1c less than (\<) 7% or greater than (\>) 10% at screening * At the time of screening age \<legal age of majority * Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method * Type 1 diabetes mellitus * Treatment with an antidiabetic pharmacological agent other than metformin within the 3 months preceding the screening * FPG at screening \>250 milligram per deciliter (mg/dL) (\>13.9 millimole per liter \[mmol/L\]) * Body mass index less than or equal to (\<)20 kilogram per square meter (kg/m\^2) * Weight change of more than 5 kg during the 3 months preceding the screening visit * History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease * History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening * Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening * Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization * Known history of drug or alcohol abuse within 6 months prior to the time of screening * Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period * Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic or diastolic blood pressure \>180 millimeter of mercury (mmHg) or \>95 mmHg, respectively * Laboratory findings at the time of screening: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP): \>2 times upper limit of the normal (ULN) laboratory range; amylase and/or lipase: \>3 times ULN; total bilirubin: \>1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin \<11 gram/deciliter and/or neutrophils \<1500 per cubic millimeter (mm\^3) and/or platelets \<100000/mm\^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb) and positive serum pregnancy test in females of childbearing potential * Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram (ECG) or vital signs at the time of screening that in the judgment of the investigator or any sub-investigator precludes safe completion of the study or constrains efficacy assessment * Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements, such as scheduled visits, being able to do self-injections), likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol) * Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, rimonabant, exenatide, dipeptidylpeptidase-4 (DPP-IV) inhibitor, insulin) within 3 months prior to the time of screening * Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening * Use of any investigational drug within 3 months prior to study * Any previous treatment with lixisenatide or participation in any previous study with lixisenatide * Renal impairment defined with creatinine \>1.4 mg/dL in women and creatinine \>1.5 mg/dL in men * Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis and gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening * Allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past (for example, exenatide, liraglutide) or to metacresol * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | Baseline, Week 24 | Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | Week 24 | The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. |
| Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | Week 24 | The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. |
| Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period | Baseline up to Week 24 | Routine fasting self-measured plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline, Week 24 | Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. |
| Change From Baseline in Body Weight at Week 24 | Baseline, Week 24 | Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | Baseline, Week 24 | The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. |
| Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | First dose of study drug up to 3 days after the last dose administration, for up to 112 weeks | 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. |
Countries
Brazil, Chile, Colombia, Estonia, Germany, Italy, Lithuania, Malaysia, Mexico, Philippines, Poland, Romania, Slovakia, Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 75 centers in 15 countries between September 29, 2008 and January 27, 2011. The overall duration of treatment was at least 76 weeks (24 weeks main double-blind treatment; variable double-blind extension treatment).
Pre-assignment details
A total of 884 patients were screened of which 400 (45.2%) were screen failures; main reason for screen failure was glycosylated hemoglobin (HbA1c) values being out of the defined protocol range (greater than or equal to 7 percent \[%\] and less than or equal to 10%). A total of 484 patients were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Two-step Titration) 2-step initiation regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. | 79 |
| Placebo (One-step Titration) 1-step initiation regimen of volume matching placebo: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment. | 81 |
| Lixisenatide (Two-step Titration) 2-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to the end of treatment. | 161 |
| Lixisenatide (One-step Titration) 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, then 20 mcg QD up to the end of treatment. | 161 |
| Total | 482 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 | 19 | 14 |
| Overall Study | Familial and Personal Reasons | 5 | 3 | 5 | 4 |
| Overall Study | Lack of Efficacy | 1 | 4 | 3 | 2 |
| Overall Study | Poor Compliance to Protocol | 1 | 1 | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
| Overall Study | Randomized but not Treated | 1 | 1 | 0 | 0 |
| Overall Study | Study Site Reason | 0 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 6 | 9 | 7 |
Baseline characteristics
| Characteristic | Placebo (Two-step Titration) | Placebo (One-step Titration) | Lixisenatide (Two-step Titration) | Lixisenatide (One-step Titration) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 8.8 | 57.5 years STANDARD_DEVIATION 10.8 | 54.6 years STANDARD_DEVIATION 8.9 | 55.4 years STANDARD_DEVIATION 8.9 | 56.1 years STANDARD_DEVIATION 9.3 |
| Body Mass Index (BMI) | 32.38 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.04 | 32.35 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.86 | 32.06 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.84 | 32.99 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.8 | 32.47 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.38 |
| Body Weight | 87.45 kilogram STANDARD_DEVIATION 16.32 | 88.28 kilogram STANDARD_DEVIATION 18.43 | 87.41 kilogram STANDARD_DEVIATION 16.9 | 90.21 kilogram STANDARD_DEVIATION 18.95 | 88.50 kilogram STANDARD_DEVIATION 17.77 |
| Duration of Diabetes | 6.68 years STANDARD_DEVIATION 5.33 | 5.77 years STANDARD_DEVIATION 4 | 6.01 years STANDARD_DEVIATION 4.6 | 5.77 years STANDARD_DEVIATION 3.85 | 6.00 years STANDARD_DEVIATION 4.4 |
| Fasting Plasma Glucose (FPG) | 9.60 millimole per liter (mmol/L) STANDARD_DEVIATION 2.06 | 9.31 millimole per liter (mmol/L) STANDARD_DEVIATION 1.82 | 9.54 millimole per liter (mmol/L) STANDARD_DEVIATION 2.5 | 9.56 millimole per liter (mmol/L) STANDARD_DEVIATION 2.02 | 9.52 millimole per liter (mmol/L) STANDARD_DEVIATION 2.17 |
| Glycosylated Hemoglobin (HbA1c) | 8.03 percentage of hemoglobin STANDARD_DEVIATION 0.81 | 8.02 percentage of hemoglobin STANDARD_DEVIATION 0.84 | 8.10 percentage of hemoglobin STANDARD_DEVIATION 0.88 | 7.99 percentage of hemoglobin STANDARD_DEVIATION 0.87 | 8.04 percentage of hemoglobin STANDARD_DEVIATION 0.86 |
| Race/Ethnicity, Customized Ethnicity: Hispanic | 24 participants | 22 participants | 55 participants | 44 participants | 145 participants |
| Race/Ethnicity, Customized Ethnicity: Non Hispanic | 55 participants | 59 participants | 106 participants | 117 participants | 337 participants |
| Race/Ethnicity, Customized Race: Asian/Oriental | 5 participants | 4 participants | 11 participants | 13 participants | 33 participants |
| Race/Ethnicity, Customized Race: Black | 0 participants | 1 participants | 2 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Race: Caucasian/White | 72 participants | 76 participants | 146 participants | 141 participants | 435 participants |
| Race/Ethnicity, Customized Race: Other | 2 participants | 0 participants | 2 participants | 6 participants | 10 participants |
| Sex: Female, Male Female | 43 Participants | 45 Participants | 89 Participants | 90 Participants | 267 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 72 Participants | 71 Participants | 215 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 | 51 / 79 | 53 / 81 | 104 / 160 | 119 / 161 | 101 / 161 | 220 / 322 |
| serious Total, serious adverse events | 13 / 79 | 9 / 81 | 22 / 160 | 21 / 161 | 16 / 161 | 37 / 322 |
Outcome results
Primary
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required. The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol
Time frame: Baseline, Week 24
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 24 | -0.42 percentage of hemoglobin | Standard Error 0.099 |
| Lixisenatide (Two-Step Titration) | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.83 percentage of hemoglobin | Standard Error 0.099 |
| Lixisenatide (One-Step Titration) | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.92 percentage of hemoglobin | Standard Error 0.101 |
Comparison: To detect a difference of 0.5% (or 0.4%) in absolute change from baseline in HbA1c at Week 24 between 1 lixisenatide arm and placebo (combined), 150 patients per group would provide a power of 91% (or 75%) assuming common standard deviation of 1.3% with 2-sided test at 5% significance level.~Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (\<8.0,\>=8.0%) and screening BMI (\<30,\>=30 kg/m\^2), country as fixed effects, baseline HbA1c as covariate.p-value: <0.000195% CI: [-0.583, -0.232]ANCOVA
Comparison: To detect a difference of 0.5% (or 0.4%) in absolute change from baseline in HbA1c at Week 24 between 1 lixisenatide arm and placebo (combined), 150 patients per group would provide a power of 91% (or 75%) assuming common standard deviation of 1.3% with 2-sided test at 5% significance level.~Analysis of co-variance (ANCOVA) included treatment arms, randomization strata of screening HbA1c (\<8.0,\>=8.0%) and screening BMI (\<30,\>=30 kg/m\^2), country as fixed effects, baseline HbA1c as covariate.p-value: <0.000195% CI: [-0.67, -0.317]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time frame: Baseline, Week 24
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.The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Body Weight at Week 24 | -1.63 kilogram | Standard Error 0.385 |
| Lixisenatide (Two-Step Titration) | Change From Baseline in Body Weight at Week 24 | -2.68 kilogram | Standard Error 0.385 |
| Lixisenatide (One-Step Titration) | Change From Baseline in Body Weight at Week 24 | -2.63 kilogram | Standard Error 0.389 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time frame: Baseline, Week 24
Population: mITT population. Missing data was imputed using last observation carried forward (LOCF). Here, number of patients analyzed = patients with baseline and at least 1 post-baseline FPG assessment during on-treatment period.The Placebo (Two-step Titration)andPlacebo (One-step Titration)Arms/Groups were combined as pre-specified in the study protocol
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | 0.11 mmol/L | Standard Error 0.209 |
| Lixisenatide (Two-Step Titration) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -0.56 mmol/L | Standard Error 0.208 |
| Lixisenatide (One-Step Titration) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -0.53 mmol/L | Standard Error 0.212 |
Secondary
Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
Routine fasting self-measured plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time frame: Baseline up to Week 24
Population: mITT population. The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period | 4.4 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period | 3.1 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period | 1.3 percentage of participants |
Secondary
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time frame: Week 24
Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 24.1 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 42.1 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 47.4 percentage of participants |
Secondary
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time frame: Week 24
Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 7.6 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 20.4 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 25.6 percentage of participants |
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, for up to 112 weeks
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.The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Combined) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic hypoglycemia | 12 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 | 12 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 | 6 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 24
The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.
Time frame: Baseline, Week 24
Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.The Placebo (Two-step Titration) and Placebo (One-step Titration) Arms/Groups were combined as pre-specified in the study protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 15.2 percentage of participants |
| Lixisenatide (Two-Step Titration) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 25.8 percentage of participants |
| Lixisenatide (One-Step Titration) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 19.6 percentage of participants |