Diabetes Mellitus, Type 2
Conditions
Keywords
hyperglycemia, GLP-1, metformin
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 as an add-on treatment to metformin in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24. The secondary objectives are to assess the effect of lixisenatide, in comparison to placebo, when administered in the evening within 1 hour prior to the meal in terms of HbA1c reduction, percentage of patients reaching HbA1c less than (\<) 7 percent (%), percentage of patients reaching HbA1c less than or equal to 6.5%, fasting plasma glucose (FPG), plasma glucose, plasma insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test (only in morning injection arms), body weight, beta-cell function assessed by homeostasis model assessment (HOMA)-beta, fasting plasma insulin (FPI) and adiponectin; to evaluate safety, tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development, beta-cell function 4 weeks after study drug discontinuation (only in patients from the morning injection arms in some selected centers).
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 patient.
Interventions
DRUGLixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding meal (either breakfast or dinner).
DRUGPlacebo
Self administered by subcutaneous injections once daily within the hour preceding meal (either breakfast or dinner).
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 before screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 gram/ day (g/day) for at least 3 months prior to screening visit
Exclusion criteria
* HbA1c \<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 (BMI) \<=20 kilogram per square meter (kg/m\^2) * Weight change of \>5 kg during the 3 months preceding the study 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 blood pressure 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 upper limit of 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 \<100 000/mm\^3; positive test for Hepatitis B surface antigen and/or Hepatitis C antibody; positive serum pregnancy test in females of child bearing potential * Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram, 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 other oral or injectable antidiabetic or hypoglycemic agents other than metformin (for example, sulfonylurea, alpha glucosidase inhibitor, other thiazolidinediones, rimonabant, exenatide, dipeptidyl-peptidase-4 inhibitors, insulin) within 3 months prior to the time of screening * Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 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 a 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 Modified Intent-to-treat (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 C-Peptide 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 last dosing day 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. |
| Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period | Baseline up to Week 24 | Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>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. |
| 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. |
| 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 2-Hour Postprandial Plasma Glucose (PPG) at Week 24 | Baseline, Week 24 | The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the 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. |
| 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. |
| Change From Baseline in Fasting Plasma Insulin (FPI) 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 2-Hour Postprandial Plasma Insulin (PPI) 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 the last dosing day of the 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. |
| Change From Baseline in Fasting Proinsulin 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 last dosing day 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. |
| Change From Baseline in 2-Hour Postprandial Proinsulin 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 last dosing day 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. |
| Change From Baseline in 2-Hour Postprandial C-Peptide 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 last dosing day 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. |
| Change From Baseline in Fasting Glucagon 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 last dosing day 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. |
| Change From Baseline in 2-Hour Postprandial Glucagon 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 last dosing day 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. |
| Change From Baseline in Adiponectin 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. |
| Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24 | Baseline, Week 24 | Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin \[micro unit per milliliter\]) divided by (FPG \[mmol/L\] minus 3.5). 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 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 |
|---|---|---|
| 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. |
| 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. |
| Change From Baseline in Glucose Excursion at Week 24 | Baseline, Week 24 | Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day 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. |
Countries
Australia, Canada, Chile, Croatia, Czechia, Germany, Mexico, Morocco, Philippines, Romania, Russia, South Africa, Spain, Ukraine, United States, Venezuela
Participant flow
Recruitment details
The study was conducted at 133 centers in 16 countries between June 30, 2008 and March 09, 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 1374 patients were screened of which 694 (50.5%) 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 680 patients were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Combined) Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo. | 170 |
| Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. | 255 |
| Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment. | 255 |
| Total | 680 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 21 | 26 |
| Overall Study | Familial and Personal Reasons | 5 | 0 | 5 | 2 |
| Overall Study | Investigator's Decision | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 8 | 8 | 6 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 | 0 |
| Overall Study | Poor Compliance to Protocol | 3 | 3 | 4 | 16 |
| Overall Study | Protocol Violation | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 7 | 15 | 20 |
Baseline characteristics
| Characteristic | Placebo (Combined) | Total | Lixisenatide (Evening Injection) | Lixisenatide (Morning Injection) |
|---|---|---|---|---|
| 2-hour Postprandial C-peptide | 2.46 nmol/L STANDARD_DEVIATION 1.08 | 2.48 nmol/L STANDARD_DEVIATION 1.12 | 2.42 nmol/L STANDARD_DEVIATION 1.16 | 2.56 nmol/L STANDARD_DEVIATION 1.11 |
| 2-hour Postprandial Glucagon | 101.30 ng/L STANDARD_DEVIATION 33.88 | 101.21 ng/L STANDARD_DEVIATION 34.17 | 100.90 ng/L STANDARD_DEVIATION 34.12 | 101.46 ng/L STANDARD_DEVIATION 34.54 |
| 2-hour Postprandial Plasma Glucose (PPG) | 15.51 mmol/L STANDARD_DEVIATION 3.43 | 15.53 mmol/L STANDARD_DEVIATION 3.86 | 15.46 mmol/L STANDARD_DEVIATION 4.03 | 15.62 mmol/L STANDARD_DEVIATION 3.97 |
| 2-hour Postprandial Plasma Insulin (PPI) | 374.28 pmol/L STANDARD_DEVIATION 266.55 | 378.30 pmol/L STANDARD_DEVIATION 289.51 | 378.67 pmol/L STANDARD_DEVIATION 328.19 | 380.53 pmol/L STANDARD_DEVIATION 260.96 |
| 2-hour Postprandial Proinsulin | 83.48 pmol/L STANDARD_DEVIATION 58.02 | 81.15 pmol/L STANDARD_DEVIATION 55.05 | 77.19 pmol/L STANDARD_DEVIATION 53.44 | 83.71 pmol/L STANDARD_DEVIATION 54.65 |
| Adiponectin | 5.61 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 3.26 | 5.34 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 3.01 | 5.25 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 2.93 | 5.25 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 2.9 |
| Age, Continuous | 55.0 years STANDARD_DEVIATION 9.4 | 54.7 years STANDARD_DEVIATION 9.7 | 54.8 years STANDARD_DEVIATION 10.4 | 54.5 years STANDARD_DEVIATION 9.2 |
| Body Mass Index (BMI) | 33.12 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.45 | 32.91 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.36 | 32.47 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.77 | 33.22 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.85 |
| Body Weight | 90.15 kilogram (kg) STANDARD_DEVIATION 20.14 | 89.71 kilogram (kg) STANDARD_DEVIATION 20.7 | 89.05 kilogram (kg) STANDARD_DEVIATION 20.74 | 90.09 kilogram (kg) STANDARD_DEVIATION 21.1 |
| Duration of Diabetes | 5.87 years STANDARD_DEVIATION 4.72 | 6.11 years STANDARD_DEVIATION 5.17 | 6.21 years STANDARD_DEVIATION 5.4 | 6.18 years STANDARD_DEVIATION 5.25 |
| Duration of Metformin Treatment | 3.34 years STANDARD_DEVIATION 3.45 | 3.61 years STANDARD_DEVIATION 3.59 | 3.68 years STANDARD_DEVIATION 3.9 | 3.73 years STANDARD_DEVIATION 3.34 |
| Fasting C-peptide | 0.90 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.36 | 0.94 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.41 | 0.94 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.43 | 0.97 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.43 |
| Fasting Glucagon | 87.92 nanogram per liter (ng/L) STANDARD_DEVIATION 29.05 | 88.51 nanogram per liter (ng/L) STANDARD_DEVIATION 29.88 | 88.53 nanogram per liter (ng/L) STANDARD_DEVIATION 27.3 | 88.89 nanogram per liter (ng/L) STANDARD_DEVIATION 32.9 |
| Fasting Plasma Glucose (FPG) | 9.51 millimole per liter (mmol/L) STANDARD_DEVIATION 2.28 | 9.40 millimole per liter (mmol/L) STANDARD_DEVIATION 2.22 | 9.31 millimole per liter (mmol/L) STANDARD_DEVIATION 2.25 | 9.43 millimole per liter (mmol/L) STANDARD_DEVIATION 2.15 |
| Fasting Plasma Insulin (FPI) | 75.79 picomole per liter (pmol/L) STANDARD_DEVIATION 48.02 | 79.53 picomole per liter (pmol/L) STANDARD_DEVIATION 60.84 | 77.90 picomole per liter (pmol/L) STANDARD_DEVIATION 65.46 | 83.68 picomole per liter (pmol/L) STANDARD_DEVIATION 63.6 |
| Fasting Proinsulin | 31.68 pmol/L STANDARD_DEVIATION 20.1 | 33.16 pmol/L STANDARD_DEVIATION 21.16 | 32.35 pmol/L STANDARD_DEVIATION 18.45 | 34.93 pmol/L STANDARD_DEVIATION 24.14 |
| Gender Female | 89 Participants | 387 Participants | 141 Participants | 157 Participants |
| Gender Male | 81 Participants | 293 Participants | 114 Participants | 98 Participants |
| Glucose Excursion | 5.64 mmol/L STANDARD_DEVIATION 2.81 | 5.87 mmol/L STANDARD_DEVIATION 3.04 | 5.80 mmol/L STANDARD_DEVIATION 3.13 | 6.09 mmol/L STANDARD_DEVIATION 3.09 |
| Glycosylated Hemoglobin (HbA1c) | 8.06 percentage of hemoglobin STANDARD_DEVIATION 0.9 | 8.06 percentage of hemoglobin STANDARD_DEVIATION 0.89 | 8.09 percentage of hemoglobin STANDARD_DEVIATION 0.91 | 8.04 percentage of hemoglobin STANDARD_DEVIATION 0.86 |
| Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) | 41.48 percentage of normal beta cells function STANDARD_DEVIATION 42.12 | 43.38 percentage of normal beta cells function STANDARD_DEVIATION 40.38 | 45.21 percentage of normal beta cells function STANDARD_DEVIATION 46.09 | 42.82 percentage of normal beta cells function STANDARD_DEVIATION 32.33 |
| Metformin Daily Dose | 2001.18 milligram (mg) STANDARD_DEVIATION 439.7 | 1967.10 milligram (mg) STANDARD_DEVIATION 430.22 | 1942.65 milligram (mg) STANDARD_DEVIATION 406.17 | 1968.82 milligram (mg) STANDARD_DEVIATION 446.99 |
| Race/Ethnicity, Customized Ethnicity: Hispanic | 49 participants | 243 participants | 98 participants | 96 participants |
| Race/Ethnicity, Customized Ethnicity: Non Hispanic | 121 participants | 437 participants | 157 participants | 159 participants |
| Race/Ethnicity, Customized Race: Asian/Oriental | 11 participants | 53 participants | 20 participants | 22 participants |
| Race/Ethnicity, Customized Race: Black | 4 participants | 17 participants | 6 participants | 7 participants |
| Race/Ethnicity, Customized Race: Caucasian/White | 155 participants | 604 participants | 228 participants | 221 participants |
| Race/Ethnicity, Customized Race: Other | 0 participants | 6 participants | 1 participants | 5 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 | 45 / 85 | 50 / 85 | 95 / 170 | 182 / 255 | 169 / 255 | 351 / 510 |
| serious Total, serious adverse events | 2 / 85 | 9 / 85 | 11 / 170 | 21 / 255 | 26 / 255 | 47 / 510 |
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 Modified Intent-to-treat (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: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 | -0.38 percentage of hemoglobin | Standard Error 0.075 |
| Lixisenatide (Morning Injection) | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.87 percentage of hemoglobin | Standard Error 0.065 |
| Lixisenatide (Evening Injection) | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.75 percentage of hemoglobin | Standard Error 0.066 |
Comparison: To detect 0.5%(or 0.4%) difference between 1 lixisenatide arm and placebo(combined), 225 patients in lixisenatide arm, 170 in placebo(combined) would provide a power of 97% (or 87%) assuming common standard deviation=1.3% with 2-sided test at 5% significance. 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: [-0.657, -0.312]ANCOVA
Comparison: To detect 0.5%(or 0.4%) difference between 1 lixisenatide arm and placebo(combined), 225 patients in lixisenatide arm, 170 in placebo(combined) would provide a power of 97% (or 87%) assuming common standard deviation=1.3% with 2-sided test at 5% significance. 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: [-0.54, -0.193]ANCOVA
Secondary
Change From Baseline in 2-Hour Postprandial C-Peptide 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 last dosing day 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline C-peptide assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in 2-Hour Postprandial C-Peptide at Week 24 | -0.20 nmol/L | Standard Error 0.137 |
| Lixisenatide (Morning Injection) | Change From Baseline in 2-Hour Postprandial C-Peptide at Week 24 | -0.46 nmol/L | Standard Error 0.097 |
Secondary
Change From Baseline in 2-Hour Postprandial Glucagon 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 last dosing day 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucagon assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in 2-Hour Postprandial Glucagon at Week 24 | -12.79 ng/L | Standard Error 3.551 |
| Lixisenatide (Morning Injection) | Change From Baseline in 2-Hour Postprandial Glucagon at Week 24 | -27.04 ng/L | Standard Error 2.467 |
Secondary
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline 2-hour PPG assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24 | -1.41 mmol/L | Standard Error 0.588 |
| Lixisenatide (Morning Injection) | Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24 | -5.92 mmol/L | Standard Error 0.415 |
Secondary
Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) 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 the last dosing day of the 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline PPI assessment during on-treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) at Week 24 | -25.67 pmol/L | Standard Error 38.028 |
| Lixisenatide (Morning Injection) | Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) at Week 24 | -87.24 pmol/L | Standard Error 24.885 |
Secondary
Change From Baseline in 2-Hour Postprandial Proinsulin 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 last dosing day 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in 2-Hour Postprandial Proinsulin at Week 24 | -6.83 pmol/L | Standard Error 5.253 |
| Lixisenatide (Morning Injection) | Change From Baseline in 2-Hour Postprandial Proinsulin at Week 24 | -18.88 pmol/L | Standard Error 3.406 |
Secondary
Change From Baseline in Adiponectin 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 adiponectin assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Adiponectin at Week 24 | 0.54 mcg/mL | Standard Error 0.183 |
| Lixisenatide (Morning Injection) | Change From Baseline in Adiponectin at Week 24 | 0.55 mcg/mL | Standard Error 0.159 |
| Lixisenatide (Evening Injection) | Change From Baseline in Adiponectin at Week 24 | 0.58 mcg/mL | Standard Error 0.16 |
Secondary
Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24
Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin \[micro unit per milliliter\]) divided by (FPG \[mmol/L\] minus 3.5). 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 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 HOMA-beta assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24 | -4.16 % of normal beta cells function | Standard Error 2.823 |
| Lixisenatide (Morning Injection) | Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24 | 7.96 % of normal beta cells function | Standard Error 2.45 |
| Lixisenatide (Evening Injection) | Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24 | 4.80 % of normal beta cells function | Standard Error 2.486 |
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Body Weight at Week 24 | -1.64 kilogram | Standard Error 0.269 |
| Lixisenatide (Morning Injection) | Change From Baseline in Body Weight at Week 24 | -2.01 kilogram | Standard Error 0.234 |
| Lixisenatide (Evening Injection) | Change From Baseline in Body Weight at Week 24 | -2.02 kilogram | Standard Error 0.236 |
Secondary
Change From Baseline in Fasting C-Peptide 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 last dosing day 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline C-peptide assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Fasting C-Peptide at Week 24 | -0.13 nmol/L | Standard Error 0.031 |
| Lixisenatide (Morning Injection) | Change From Baseline in Fasting C-Peptide at Week 24 | -0.10 nmol/L | Standard Error 0.02 |
Secondary
Change From Baseline in Fasting Glucagon 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 last dosing day 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucagon assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Fasting Glucagon at Week 24 | -13.53 ng/L | Standard Error 3.054 |
| Lixisenatide (Morning Injection) | Change From Baseline in Fasting Glucagon at Week 24 | -13.27 ng/L | Standard Error 2.074 |
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -0.25 mmol/L | Standard Error 0.166 |
| Lixisenatide (Morning Injection) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -1.19 mmol/L | Standard Error 0.145 |
| Lixisenatide (Evening Injection) | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -0.81 mmol/L | Standard Error 0.146 |
Secondary
Change From Baseline in Fasting Plasma Insulin (FPI) 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 LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline plasma insulin assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24 | -6.23 pmol/L | Standard Error 3.254 |
| Lixisenatide (Morning Injection) | Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24 | -5.09 pmol/L | Standard Error 2.812 |
| Lixisenatide (Evening Injection) | Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24 | -1.88 pmol/L | Standard Error 2.862 |
Secondary
Change From Baseline in Fasting Proinsulin 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 last dosing day 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Combined) | Change From Baseline in Fasting Proinsulin at Week 24 | -3.78 pmol/L | Standard Error 2.246 |
| Lixisenatide (Morning Injection) | Change From Baseline in Fasting Proinsulin at Week 24 | -7.78 pmol/L | Standard Error 1.414 |
Secondary
Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period
Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period | 10.6 percentage of participants |
| Lixisenatide (Morning Injection) | Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period | 2.7 percentage of participants |
| Lixisenatide (Evening Injection) | Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period | 3.9 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 22.0 percentage of participants |
| Lixisenatide (Morning Injection) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 43.0 percentage of participants |
| Lixisenatide (Evening Injection) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 40.6 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 10.4 percentage of participants |
| Lixisenatide (Morning Injection) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 23.8 percentage of participants |
| Lixisenatide (Evening Injection) | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 19.2 percentage of participants |
Other Pre-specified
Change From Baseline in Glucose Excursion at Week 24
Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day 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.
Time frame: Baseline, Week 24
Population: Subgroup for standardized meal teat. 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 24 | -0.76 mmol/L | Standard Error 0.483 |
| Lixisenatide (Morning Injection) | Change From Baseline in Glucose Excursion at Week 24 | -4.64 mmol/L | Standard Error 0.34 |
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 | 0 participants |
| Placebo (Combined) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe Symptomatic Hypoglycemia | 0 participants |
| Lixisenatide (Morning Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic Hypoglycemia | 4 participants |
| Lixisenatide (Morning Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe Symptomatic Hypoglycemia | 0 participants |
| Lixisenatide (Evening Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic Hypoglycemia | 4 participants |
| Lixisenatide (Evening Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe Symptomatic Hypoglycemia | 0 participants |
| Lixisenatide (Morning Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic Hypoglycemia | 18 participants |
| Lixisenatide (Morning Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe Symptomatic Hypoglycemia | 0 participants |
| Lixisenatide (Evening Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic Hypoglycemia | 22 participants |
| Lixisenatide (Evening Injection) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe Symptomatic Hypoglycemia | 0 participants |
| Lixisenatide (Combined) | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic Hypoglycemia | 40 participants |
| Lixisenatide (Combined) | 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 11.3 percentage of participants |
| Lixisenatide (Morning Injection) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 14.9 percentage of participants |
| Lixisenatide (Evening Injection) | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 19.3 percentage of participants |