Diabetes Mellitus, Type 2
Conditions
Keywords
hyperglycemia, GLP-1, metformin
Brief summary
The purpose of this study is to compare the benefits and risks of lixisenatide (AVE0010) in comparison to exenatide (Byetta®), 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 in comparison to exenatide (Byetta®), as an add-on treatment to metformin, on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24. The secondary objectives are to assess the effects of lixisenatide on percentage of patients reaching HbA1c less than 7 percent (%) or HbA1c less than or equal to (\<=) 6.5%, fasting plasma glucose (FPG), body weight; to evaluate safety, tolerability and to assess the impact of gastrointestinal tolerance on quality of life (QoL) (patient assessment of upper gastrointestinal disorders - quality of life \[PAGI-QOL\]).
Detailed description
Patients who complete the 24-week main open-label treatment would undergo a variable open-label extension treatment, which ends for all patients at approximately the scheduled date of Week 76 visit (Visit 24) for the last randomized patient.
Interventions
DRUGLixisenatide (AVE0010)
Self administered by subcutaneous injections once daily within the hour preceding breakfast.
DEVICEPen auto-injector
DRUGExenatide
Self administered by subcutaneous injections twice daily within the hour preceding breakfast and within the hour preceding dinner.
DEVICEPrefilled pen 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
NONE
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 per 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 another antidiabetic pharmacological agent 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) less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2) * Weight change of \>5 kg during the 3 months preceding the study * 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 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 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 \<100 000/ mm\^3; positive test for Hepatitis B surface antigen and/or Hepatitis C antibody; and positive serum pregnancy test in females of childbearing 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 attending 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 than metformin (for example, sulfonylurea, alpha-glucosidase inhibitor, thiazolidinedione, 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 * Participation in any previous study with lixisenatide * Renal impairment defined with serum creatinine \>1.4 mg/dL in women and serum 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
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 11 (Week 24) or Day 169 if Visit 11 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 11 (Week 24) or Day 169 if Visit 11 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 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 11 (Week 24) or Day 169 if Visit 11 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 11 (Week 24) or Day 169 if Visit 11 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-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. |
| 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 11 (Week 24) or Day 169 if Visit 11 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 |
|---|---|---|
| Quality of Life: Change From Baseline in Patient's Satisfaction to Treatment (PAGI-QOL) at Week 24 | Baseline, Week 24 | PAGI-QOL: a 30-item self-administered questionnaire to measure health related QOL of patients with upper gastrointestinal disorders during past 2 weeks. Consists of 5 sub-scales. Each item rated on a 0-5 point Likert scale (0 \[none of the time\] to 5 \[all the time\]). Sub-scale score calculated by dividing sum of all items of subscale by number of items in the sub-scale. Total score calculated by taking mean of sub-scale scores. Sub-scale score and total score ranges from 0=none of the time (lowest score) to 5=all of the time (highest score) with lower scores indicating better QOL. The on-treatment period for this 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 11 (Week 24) or Day 169 if Visit 11 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 116 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 an event with clinical symptoms that were considered to result from hypoglycemia 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 11 (Week 24) or Day 169 if Visit 11 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. |
Countries
Argentina, Austria, Brazil, Colombia, Denmark, Finland, Germany, Greece, Hungary, Italy, Netherlands, Norway, Poland, Puerto Rico, Russia, Spain, Sweden, United States
Participant flow
Recruitment details
The study was conducted at 122 centers in 18 countries between June 23, 2008 and November 18, 2010. The overall duration of treatment was at least 76 weeks (24 weeks main open-label treatment; variable open-label extension treatment).
Pre-assignment details
A total of 1243 patients were screened of which 604 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 639 patients were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Lixisenatide 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. | 318 |
| Exenatide 1-step initiation regimen of exenatide: 5 mcg BID subcutaneously for 4 weeks, followed by 10 mcg BID up to the end of treatment. | 316 |
| Total | 634 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 45 | 45 |
| Overall Study | Familial or Personal Reasons | 12 | 15 |
| Overall Study | Lack of Efficacy | 19 | 6 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Poor Compliance to Protocol | 7 | 13 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Serious Noncompliance | 2 | 3 |
| Overall Study | Sponsor Decision | 9 | 8 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
Baseline characteristics
| Characteristic | Lixisenatide | Exenatide | Total |
|---|---|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 9.2 | 57.6 years STANDARD_DEVIATION 10.7 | 57.4 years STANDARD_DEVIATION 9.9 |
| Body Mass Index (BMI) | 33.68 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.27 | 33.51 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.54 | 33.60 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.4 |
| Body Weight | 94.0 kilogram (kg) STANDARD_DEVIATION 19.6 | 96.1 kilogram (kg) STANDARD_DEVIATION 22.5 | 95.0 kilogram (kg) STANDARD_DEVIATION 21.13 |
| Daily Metformin Dose | 2020.20 milligram (mg) STANDARD_DEVIATION 459.41 | 2058.39 milligram (mg) STANDARD_DEVIATION 453.23 | 2039.24 milligram (mg) STANDARD_DEVIATION 456.38 |
| Duration of Diabetes | 6.78 years STANDARD_DEVIATION 5.54 | 6.75 years STANDARD_DEVIATION 4.87 | 6.76 years STANDARD_DEVIATION 5.21 |
| Fasting Plasma Glucose (FPG) | 9.7 millimole per liter (mmol/L) STANDARD_DEVIATION 2 | 9.7 millimole per liter (mmol/L) STANDARD_DEVIATION 2.3 | 9.7 millimole per liter (mmol/L) STANDARD_DEVIATION 2.1 |
| Glycosylated Hemoglobin (HbA1c) | 7.95 percentage of hemoglobin STANDARD_DEVIATION 0.81 | 7.97 percentage of hemoglobin STANDARD_DEVIATION 0.78 | 7.96 percentage of hemoglobin STANDARD_DEVIATION 0.8 |
| Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) Total Score | 0.59 units on a scale STANDARD_DEVIATION 0.7 | 0.56 units on a scale STANDARD_DEVIATION 0.7 | 0.58 units on a scale STANDARD_DEVIATION 0.7 |
| Race/Ethnicity, Customized Ethnicity: Hispanic | 87 participants | 83 participants | 170 participants |
| Race/Ethnicity, Customized Ethnicity: Non Hispanic | 231 participants | 233 participants | 464 participants |
| Race/Ethnicity, Customized Race: Asian/Oriental | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Race: Black | 8 participants | 10 participants | 18 participants |
| Race/Ethnicity, Customized Race: Caucasian/White | 296 participants | 292 participants | 588 participants |
| Race/Ethnicity, Customized Race: Other | 11 participants | 10 participants | 21 participants |
| Sex: Female, Male Female | 167 Participants | 129 Participants | 296 Participants |
| Sex: Female, Male Male | 151 Participants | 187 Participants | 338 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 204 / 318 | 218 / 316 |
| serious Total, serious adverse events | 26 / 318 | 22 / 316 |
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 11 (Week 24) or Day 169 if Visit 11 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: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 |
|---|---|---|---|
| Lixisenatide | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.79 percentage of hemoglobin | Standard Error 0.053 |
| Exenatide | Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.96 percentage of hemoglobin | Standard Error 0.054 |
Comparison: To detect that upper confidence limit of 2-sided 95% confidence interval for least square (LS) mean difference between the 2 arms do not exceed 0.4% HbA1c, 300 patients per group would provide 96% power assuming a standard deviation of 1.3 and true difference in HbA1c between the 2 arms as 0.95% CI: [0.033, 0.297]
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 11 (Week 24) or Day 169 if Visit 11 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 |
|---|---|---|---|
| Lixisenatide | Change From Baseline in Body Weight at Week 24 | -2.96 kilogram | Standard Error 0.231 |
| Exenatide | Change From Baseline in Body Weight at Week 24 | -3.98 kilogram | Standard Error 0.232 |
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 11 (Week 24) or Day 169 if Visit 11 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 |
|---|---|---|---|
| Lixisenatide | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -1.22 mmol/L | Standard Error 0.116 |
| Exenatide | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -1.45 mmol/L | Standard Error 0.119 |
Secondary
Percentage of Patients Requiring Rescue Therapy During 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) |
|---|---|---|
| Lixisenatide | Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period | 2.2 percentage of participants |
| Exenatide | Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period | 3.8 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 11 (Week 24) or Day 169 if Visit 11 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) |
|---|---|---|
| Lixisenatide | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 48.5 percentage of participants |
| Exenatide | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24 | 49.8 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 11 (Week 24) or Day 169 if Visit 11 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) |
|---|---|---|
| Lixisenatide | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 28.5 percentage of participants |
| Exenatide | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24 | 35.4 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 an event with clinical symptoms that were considered to result from hypoglycemia 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 116 weeks
Population: Safety population included all randomized patients who received at least 1 dose of study drug, regardless of the amount of treatment administered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lixisenatide | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic Hypoglycemia | 16 participants |
| Lixisenatide | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Severe Symptomatic Hypoglycemia | 0 participants |
| Exenatide | Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia | Symptomatic Hypoglycemia | 46 participants |
| Exenatide | 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 11 (Week 24) or Day 169 if Visit 11 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) |
|---|---|---|
| Lixisenatide | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 25.1 percentage of participants |
| Exenatide | Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24 | 31.4 percentage of participants |
Other Pre-specified
Quality of Life: Change From Baseline in Patient's Satisfaction to Treatment (PAGI-QOL) at Week 24
PAGI-QOL: a 30-item self-administered questionnaire to measure health related QOL of patients with upper gastrointestinal disorders during past 2 weeks. Consists of 5 sub-scales. Each item rated on a 0-5 point Likert scale (0 \[none of the time\] to 5 \[all the time\]). Sub-scale score calculated by dividing sum of all items of subscale by number of items in the sub-scale. Total score calculated by taking mean of sub-scale scores. Sub-scale score and total score ranges from 0=none of the time (lowest score) to 5=all of the time (highest score) with lower scores indicating better QOL. The on-treatment period for this 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 11 (Week 24) or Day 169 if Visit 11 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 PAGI-QOL assessment during on-treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide | Quality of Life: Change From Baseline in Patient's Satisfaction to Treatment (PAGI-QOL) at Week 24 | -0.09 units on a scale | Standard Error 0.031 |
| Exenatide | Quality of Life: Change From Baseline in Patient's Satisfaction to Treatment (PAGI-QOL) at Week 24 | -0.06 units on a scale | Standard Error 0.032 |