Trial Outcomes & Findings for GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Basal Insulin +/- Sulfonylurea (GETGOAL-L-ASIA) (NCT NCT00866658)

Last Updated: 2016-10-11

Results Overview

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

311 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2016-10-11

Participant Flow

The study was conducted at 57 centers in 4 countries between March 10, 2009 and June 23, 2010.

A total of 437 patients were screened of which 126 (28.8%) 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 311 patients were randomized.

Participant milestones

Participant milestones
Measure	Placebo 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 Week 24.	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 Week 24.
Overall Study STARTED	157	154
Overall Study Safety Population	157	154
Overall Study Modified Intent-to-Treat(mITT)Population	157	154
Overall Study COMPLETED	144	133
Overall Study NOT COMPLETED	13	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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 Week 24.	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 Week 24.
Overall Study Adverse Event	5	14
Overall Study Lack of Efficacy	2	1
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	1	1
Overall Study Familial and Personal Reasons	4	5

Baseline Characteristics

GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Basal Insulin +/- Sulfonylurea (GETGOAL-L-ASIA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=157 Participants 2-step initiation regimen of volume matching placebo: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.	Lixisenatide n=154 Participants 2-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.	Total n=311 Participants Total of all reporting groups
Age, Continuous	58.0 years STANDARD_DEVIATION 10.1 • n=5 Participants	58.7 years STANDARD_DEVIATION 10.2 • n=7 Participants	58.4 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	85 Participants n=7 Participants	162 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	69 Participants n=7 Participants	149 Participants n=5 Participants
Race/Ethnicity, Customized Race: Asian/Oriental	157 participants n=5 Participants	154 participants n=7 Participants	311 participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Non Hispanic	157 participants n=5 Participants	154 participants n=7 Participants	311 participants n=5 Participants
Glycosylated Hemoglobin (HbA1c)	8.52 percentage of hemoglobin STANDARD_DEVIATION 0.78 • n=5 Participants	8.54 percentage of hemoglobin STANDARD_DEVIATION 0.73 • n=7 Participants	8.53 percentage of hemoglobin STANDARD_DEVIATION 0.76 • n=5 Participants
Body Weight	65.60 kilogram (kg) STANDARD_DEVIATION 12.47 • n=5 Participants	65.93 kilogram (kg) STANDARD_DEVIATION 13.00 • n=7 Participants	65.77 kilogram (kg) STANDARD_DEVIATION 12.72 • n=5 Participants
2-Hour Postprandial Plasma Glucose (PPG)	17.75 millimole per liter (mmol/L) STANDARD_DEVIATION 3.94 • n=5 Participants	17.81 millimole per liter (mmol/L) STANDARD_DEVIATION 3.36 • n=7 Participants	17.78 millimole per liter (mmol/L) STANDARD_DEVIATION 3.66 • n=5 Participants
Number of Patients With Screening HbA1c Less Than 8%	36 participants n=5 Participants	35 participants n=7 Participants	71 participants n=5 Participants
Number of Patients With Screening HbA1c Greater Than or Equal to 8%	121 participants n=5 Participants	119 participants n=7 Participants	240 participants n=5 Participants
Fasting Plasma Glucose (FPG)	7.75 mmol/L STANDARD_DEVIATION 2.25 • n=5 Participants	7.67 mmol/L STANDARD_DEVIATION 2.32 • n=7 Participants	7.71 mmol/L STANDARD_DEVIATION 2.28 • n=5 Participants
Average 7-point Self-Monitored Plasma Glucose (SMPG)	11.42 mmol/L STANDARD_DEVIATION 2.46 • n=5 Participants	11.58 mmol/L STANDARD_DEVIATION 2.51 • n=7 Participants	11.51 mmol/L STANDARD_DEVIATION 2.48 • n=5 Participants
Glucose Excursion	9.70 mmol/L STANDARD_DEVIATION 4.19 • n=5 Participants	9.72 mmol/L STANDARD_DEVIATION 3.27 • n=7 Participants	9.71 mmol/L STANDARD_DEVIATION 3.75 • n=5 Participants
Basal Insulin Treatment Duration	3.01 years STANDARD_DEVIATION 4.27 • n=5 Participants	2.94 years STANDARD_DEVIATION 3.67 • n=7 Participants	2.97 years STANDARD_DEVIATION 3.97 • n=5 Participants
Total Insulin Dose	24.11 units per day STANDARD_DEVIATION 14.18 • n=5 Participants	24.85 units per day STANDARD_DEVIATION 13.96 • n=7 Participants	24.48 units per day STANDARD_DEVIATION 14.05 • n=5 Participants
Number of Patients With Insulin Therapy at Screening Glargine	92 participants n=5 Participants	95 participants n=7 Participants	187 participants n=5 Participants
Number of Patients With Insulin Therapy at Screening Detemir	42 participants n=5 Participants	41 participants n=7 Participants	83 participants n=5 Participants
Number of Patients With Insulin Therapy at Screening Neutral Protamine Hagedorn (NPH)	21 participants n=5 Participants	18 participants n=7 Participants	39 participants n=5 Participants
Number of Patients With Insulin Therapy at Screening Premix (Mixed Insulin)	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Duration of Diabetes	14.13 years STANDARD_DEVIATION 7.72 • n=5 Participants	13.71 years STANDARD_DEVIATION 7.73 • n=7 Participants	13.92 years STANDARD_DEVIATION 7.71 • n=5 Participants
Sulfonylurea Treatment Duration	6.80 years STANDARD_DEVIATION 5.24 • n=5 Participants	5.33 years STANDARD_DEVIATION 4.83 • n=7 Participants	6.07 years STANDARD_DEVIATION 5.08 • n=5 Participants
Number of Patients With Sulfonylurea Use Yes	111 participants n=5 Participants	108 participants n=7 Participants	219 participants n=5 Participants
Number of Patients With Sulfonylurea Use No	46 participants n=5 Participants	46 participants n=7 Participants	92 participants n=5 Participants
Body Mass Index (BMI)	25.15 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.94 • n=5 Participants	25.36 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.69 • n=7 Participants	25.26 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.82 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=154 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=146 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24	0.11 percentage of hemoglobin Standard Error 0.131	-0.77 percentage of hemoglobin Standard Error 0.137

SECONDARY outcome

Timeframe: 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 2-hour PPG assessment during on-treatment period.

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo n=142 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=131 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24	-0.14 mmol/L Standard Error 0.563	-7.96 mmol/L Standard Error 0.598

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=157 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=150 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Change From Baseline in Body Weight at Week 24	0.06 kilogram Standard Error 0.271	-0.38 kilogram Standard Error 0.284

SECONDARY outcome

Timeframe: 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 average 7-point SMPG assessment during on-treatment period.

Patients recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime once in a week and the average value for the 7-time points was calculated. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo n=138 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=142 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Change From Baseline in Average 7-Point Self Monitored Plasma Glucose (SMPG) Profile at Week 24	-0.56 mmol/L Standard Error 0.271	-1.91 mmol/L Standard Error 0.272

SECONDARY outcome

Timeframe: 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 FPG assessment during on-treatment period.

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo n=157 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=148 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	0.25 mmol/L Standard Error 0.302	-0.42 mmol/L Standard Error 0.314

SECONDARY outcome

Timeframe: Screening, 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 insulin dose assessment during on-treatment period.

Change was calculated by subtracting screening value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo n=157 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=151 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Change From Screening in Total Insulin Dose at Week 24	-0.11 units per day Standard Error 0.442	-1.39 units per day Standard Error 0.458

SECONDARY outcome

Timeframe: 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 HbA1c assessment during on-treatment period.

The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo n=154 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=146 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24	5.2 percentage of participants	35.6 percentage of participants

SECONDARY outcome

Timeframe: 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 HbA1c assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=154 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=146 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24	1.3 percentage of participants	17.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: mITT population.

Routine fasting SMPG and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 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.

Outcome measures

Outcome measures
Measure	Placebo n=157 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=154 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Percentage of Patients Requiring Rescue Therapy During 24-Week Period	3.2 percentage of participants	1.3 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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 glucose excursion assessment during on-treatment period.

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 the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo n=142 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=131 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Change From Baseline in Glucose Excursion at Week 24	0.14 mmol/L Standard Error 0.542	-7.09 mmol/L Standard Error 0.576

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Placebo n=157 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=150 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24	4.5 percentage of participants	7.3 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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 less than 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.

Outcome measures

Outcome measures
Measure	Placebo n=157 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=154 Participants 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia Symptomatic hypoglycemia	37 participants	66 participants
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia Severe symptomatic hypoglycemia	0 participants	0 participants

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 71 other events

Deaths: 0 deaths

Lixisenatide

Serious events: 10 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=157 participants at risk 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=154 participants at risk 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Infections and infestations Nasopharyngitis	12.7% 20/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	13.6% 21/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.5% 10/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Metabolism and nutrition disorders Hypoglycaemia	23.6% 37/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	43.5% 67/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Dizziness	5.1% 8/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.4% 13/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Headache	1.9% 3/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	10.4% 16/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Abdominal discomfort	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 11/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Constipation	2.5% 4/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.2% 8/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Diarrhoea	2.5% 4/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.5% 10/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Dyspepsia	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 11/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Nausea	4.5% 7/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	39.6% 61/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Vomiting	1.9% 3/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	18.2% 28/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
General disorders Asthenia	7.6% 12/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.5% 10/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=157 participants at risk 2-step initiation regimen up to a maintenance dose of 20 mcg of volume matching placebo.	Lixisenatide n=154 participants at risk 2-step initiation regimen up to a maintenance dose of 20 mcg of lixisenatide.
Infections and infestations Herpes zoster oticus	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Pneumonia	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Upper respiratory tract infection	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Psychiatric disorders Completed suicide	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Cerebral infarction	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.3% 2/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Eye disorders Hyphaema	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Eye disorders Retinal haemorrhage	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Vascular disorders Hypertensive crisis	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Respiratory, thoracic and mediastinal disorders Asthma	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Colonic polyp	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Nausea	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Vomiting	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Hepatobiliary disorders Liver disorder	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Reproductive system and breast disorders Uterine prolapse	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Joint injury	0.00% 0/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.65% 1/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Lower limb fracture	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Skin laceration	0.64% 1/157 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/154 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169 days in both arms. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.