Trial Outcomes & Findings for Effects of Lixisenatide Compared to Liraglutide on the Postprandial Plasma Glucose in Patients With Type 2 Diabetes (NCT NCT01175473)

Last Updated: 2016-11-28

Results Overview

The area under the plasma glucose concentration time curve (GLU-AUC0:30-4:30h) was calculated using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\] on Day 28) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours). GLU-AUC0:30-4:30h on Day -1 was the baseline. Change in GLU-AUC0:30-4:30h = GLU-AUC0:30-4:30h on Day 28 minus GLU-AUC0:30-4:30h on Day -1.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

148 participants

Primary outcome timeframe

0.5 (8:00 clock time; prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

Results posted on

2016-11-28

Participant Flow

The study was conducted at 7 centers in Germany between August 03, 2010 and November 18, 2010.

A total of 259 patients were screened of which 111 (42.9%) were screen failures. A total of 148 patients were randomized.

Participant milestones

Participant milestones
Measure	Lixisenatide 1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) subcutaneously for 2 weeks, followed by 20 mcg QD up to Week 4.	Liraglutide 2-step initiation regimen of liraglutide: 0.6 milligram (mg) QD subcutaneously for 1 week, followed by 1.2 mg QD for 1 week, then 1.8 mg QD up to Week 4.
Overall Study STARTED	77	71
Overall Study Safety Population	77	71
Overall Study Pharmacodynamic (PD) Population	75	68
Overall Study COMPLETED	75	69
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Lixisenatide 1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) subcutaneously for 2 weeks, followed by 20 mcg QD up to Week 4.	Liraglutide 2-step initiation regimen of liraglutide: 0.6 milligram (mg) QD subcutaneously for 1 week, followed by 1.2 mg QD for 1 week, then 1.8 mg QD up to Week 4.
Overall Study Adverse Event	2	2

Baseline Characteristics

Effects of Lixisenatide Compared to Liraglutide on the Postprandial Plasma Glucose in Patients With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lixisenatide n=77 Participants 1-step initiation regimen of lixisenatide: 10 mcg QD subcutaneously for 2 weeks, followed by 20 mcg QD up to Week 4.	Liraglutide n=71 Participants 2-step initiation regimen of liraglutide: 0.6 mg QD subcutaneously for 1 week, followed by 1.2 mg QD for 1 week, then 1.8 mg QD up to Week 4.	Total n=148 Participants Total of all reporting groups
Age, Continuous	60.5 years STANDARD_DEVIATION 7.5 • n=5 Participants	59.7 years STANDARD_DEVIATION 8.5 • n=7 Participants	60.1 years STANDARD_DEVIATION 8.0 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	21 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	50 Participants n=7 Participants	99 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	76 participants n=5 Participants	71 participants n=7 Participants	147 participants n=5 Participants
Race/Ethnicity, Customized Black	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Area Under Plasma Glucose Concentration Curve From Time 0.5 Hours to 4.5 Hours (GLU-AUC0:30-4:30h)	169.41 hourmilligram per deciliter (hmg/dL) STANDARD_DEVIATION 84.03 • n=5 Participants	183.86 hourmilligram per deciliter (hmg/dL) STANDARD_DEVIATION 100.89 • n=7 Participants	176.28 hourmilligram per deciliter (hmg/dL) STANDARD_DEVIATION 92.39 • n=5 Participants
Postprandial Plasma Glucose (PPG) Excursion	88.06 milligram per deciliter (mg/dL) STANDARD_DEVIATION 29.31 • n=5 Participants	88.06 milligram per deciliter (mg/dL) STANDARD_DEVIATION 35.86 • n=7 Participants	88.06 milligram per deciliter (mg/dL) STANDARD_DEVIATION 32.47 • n=5 Participants
Pro-insulin AUC(0:30-4:30h)	5.68 hour*micro international unit/milliliter STANDARD_DEVIATION 6.25 • n=5 Participants	6.54 hour*micro international unit/milliliter STANDARD_DEVIATION 5.40 • n=7 Participants	6.09 hour*micro international unit/milliliter STANDARD_DEVIATION 5.86 • n=5 Participants
Insulin AUC(0:30-4:30h)	99.55 hour*micro international unit/milliliter STANDARD_DEVIATION 43.61 • n=5 Participants	93.24 hour*micro international unit/milliliter STANDARD_DEVIATION 57.30 • n=7 Participants	96.55 hour*micro international unit/milliliter STANDARD_DEVIATION 50.50 • n=5 Participants
C-Peptide AUC(0:30-4:30h)	10.61 hournanogram per milliliter (hng/mL) STANDARD_DEVIATION 4.44 • n=5 Participants	9.99 hournanogram per milliliter (hng/mL) STANDARD_DEVIATION 4.89 • n=7 Participants	10.31 hournanogram per milliliter (hng/mL) STANDARD_DEVIATION 4.65 • n=5 Participants
Glucagon AUC(0:30-4:30h)	27.10 hourpicogram per milliliter (hpg/mL) STANDARD_DEVIATION 60.54 • n=5 Participants	16.47 hourpicogram per milliliter (hpg/mL) STANDARD_DEVIATION 78.98 • n=7 Participants	22.05 hourpicogram per milliliter (hpg/mL) STANDARD_DEVIATION 69.87 • n=5 Participants
Glycosylated Hemoglobin (HbA1c)	7.20 percentage of hemoglobin STANDARD_DEVIATION 0.63 • n=5 Participants	7.41 percentage of hemoglobin STANDARD_DEVIATION 0.81 • n=7 Participants	7.30 percentage of hemoglobin STANDARD_DEVIATION 0.72 • n=5 Participants
Peptide YY3-36 (PYY3-36) Concentration 0.5 h	17.60 picomole per liter (pmol/L) STANDARD_DEVIATION 9.46 • n=5 Participants	17.83 picomole per liter (pmol/L) STANDARD_DEVIATION 9.29 • n=7 Participants	17.71 picomole per liter (pmol/L) STANDARD_DEVIATION 9.35 • n=5 Participants
Peptide YY3-36 (PYY3-36) Concentration 2.5 h	21.73 picomole per liter (pmol/L) STANDARD_DEVIATION 11.83 • n=5 Participants	21.02 picomole per liter (pmol/L) STANDARD_DEVIATION 9.19 • n=7 Participants	21.40 picomole per liter (pmol/L) STANDARD_DEVIATION 10.62 • n=5 Participants
Peptide YY3-36 (PYY3-36) Concentration 4.5 h	21.98 picomole per liter (pmol/L) STANDARD_DEVIATION 10.74 • n=5 Participants	20.88 picomole per liter (pmol/L) STANDARD_DEVIATION 10.66 • n=7 Participants	21.46 picomole per liter (pmol/L) STANDARD_DEVIATION 10.68 • n=5 Participants
Obestatin Concentration 0.5 h	0.24 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.12 • n=5 Participants	0.29 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.18 • n=7 Participants	0.26 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.15 • n=5 Participants
Obestatin Concentration 2.5 h	0.22 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.11 • n=5 Participants	0.26 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.15 • n=7 Participants	0.24 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.13 • n=5 Participants
Obestatin Concentration 4.5 h	0.24 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.12 • n=5 Participants	0.27 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.17 • n=7 Participants	0.25 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.15 • n=5 Participants

PRIMARY outcome

Timeframe: 0.5 (8:00 clock time; prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 0.75, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

Population: Pharmacodynamic (PD) population (modified intent-to-treat \[mITT\] population) included all randomized patients, who received at least 1 dose of lixisenatide or liraglutide, and had both a baseline assessment and at least 1 post-baseline assessment of any pharmacodynamic variable, irrespective of compliance with the study protocol and procedures.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Baseline in Area Under the Plasma Glucose Concentration Curve From Time 0.5 Hours to 4.5 Hours (GLU-AUC0:30-4:30h) at Day 28	-227.25 h*mg/dL 95% Confidence Interval 120.26 • Interval -246.88 to -207.61	-72.83 h*mg/dL 95% Confidence Interval 79.66 • Interval -93.19 to -52.46

SECONDARY outcome

Population: PD population.

PPG excursion was determined on Day -1 (Baseline) and 28 as the maximum change in PPG from time of breakfast start (time: 0.5 hours) until 4 hours later subtracted from pre-meal plasma concentration.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Baseline in Postprandial Plasma Glucose (PPG) Excursion at Day 28	-70.43 mg/dL 95% Confidence Interval 42.04 • Interval -77.83 to -63.03	-24.93 mg/dL 95% Confidence Interval 33.67 • Interval -32.57 to -17.29

SECONDARY outcome

Timeframe: 0.5 (8:00 clock time; prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 1, 1.5, 2.5, 3.5, 4.5 hours post study drug administration on Day 28

Population: PD population.

The area under the pro-insulin concentration time curve (AUC0:30-4:30h) was calculated using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\] on Day 28) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast pro-insulin concentration (time: 0.5 hours). Pro-insulin AUC0:30-4:30h on Day -1 was the baseline. Change in pro-insulin AUC0:30-4:30h = pro-insulin AUC0:30-4:30h on Day 28 minus pro-insulin AUC0:30-4:30h on Day -1.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Baseline in Pro-insulin AUC(0:30-4:30h) at Day 28	-1.27 hour*micro international unit/milliliter 95% Confidence Interval 6.18 • Interval -2.36 to -0.18	-2.47 hour*micro international unit/milliliter 95% Confidence Interval 4.86 • Interval -3.59 to -1.34

SECONDARY outcome

Population: PD population.

The area under the insulin concentration time curve (AUC0:30-4:30h) was calculated using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\] on Day 28) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast insulin concentration (time: 0.5 hours). Insulin AUC0:30-4:30h on Day -1 was the baseline. Change in insulin AUC0:30-4:30h = insulin AUC0:30-4:30h on Day 28 minus insulin AUC0:30-4:30h on Day -1.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Baseline in Insulin AUC(0:30-4:30h) at Day 28	-64.22 hour*micro international unit/milliliter 95% Confidence Interval 59.74 • Interval -78.2 to -50.24	5.34 hour*micro international unit/milliliter 95% Confidence Interval 57.82 • Interval -9.16 to 19.84

SECONDARY outcome

Population: PD population.

The area under the C-peptide concentration time curve (AUC0:30-4:30h) was calculated using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\] on Day 28) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast C-peptide concentration (time: 0.5 hours). C-peptide AUC0:30-4:30h on Day -1 was the baseline. Change in C-peptide AUC0:30-4:30h = C-peptide AUC0:30-4:30h on Day 28 minus C-peptide AUC0:30-4:30h on Day -1.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Baseline in C-Peptide AUC(0:30-4:30h) at Day 28	-5.03 h*ng/mL 95% Confidence Interval 5.97 • Interval -6.33 to -3.72	1.04 h*ng/mL 95% Confidence Interval 4.71 • Interval -0.31 to 2.39

SECONDARY outcome

Population: PD population.

The area under the glucagon concentration time curve (AUC0:30-4:30h) was calculated using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\] on Day 28) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast glucagon concentration (time: 0.5 hours). Glucagon AUC0:30-4:30h on Day -1 was the baseline. Change in glucagon AUC0:30-4:30h = glucagon AUC0:30-4:30h on Day 28 minus glucagon AUC0:30-4:30h on Day -1.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Baseline in Glucagon AUC(0:30-4:30h) at Day 28	-46.71 h*pg/mL 95% Confidence Interval 67.90 • Interval -61.6 to -31.83	-25.28 h*pg/mL 95% Confidence Interval 68.07 • Interval -40.65 to -9.9

SECONDARY outcome

Timeframe: Pre-dose (Hour 0) on Day 1 and 29 (that is, 24 hours post-dose on Day 28)

Population: PD population. Here, number of patients analyzed = patients with post-baseline HbA1c assessment.

Change = HbA1c value at Day 29 (24 hours post-dose on Day 28) minus HbA1c value at baseline (pre-dose \[Hour 0\] on Day 1).

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=67 Participants 2-step initiation regimen of liraglutide.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 29	-0.32 percentage of hemoglobin 95% Confidence Interval 0.30 • Interval -0.4 to -0.24	-0.45 percentage of hemoglobin 95% Confidence Interval 0.40 • Interval -0.54 to -0.37

SECONDARY outcome

Timeframe: 0.5 (8:00 clock time; prior to standardized breakfast), 2.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 2.5, 4.5 hours post study drug administration on Day 28

Population: PD population.

Change was calculated by subtracting time-matched baseline value from Day 28 value. Baseline value was the Day -1 time-matched PYY-36 assessment.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Time-matched Baseline in Peptide YY3-36 (PYY3-36) Concentration at Day 28 Change at Day 28: 2.5 h	-7.09 pmol/L Standard Deviation 8.38	-3.14 pmol/L Standard Deviation 6.67
Change From Time-matched Baseline in Peptide YY3-36 (PYY3-36) Concentration at Day 28 Change at Day 28: 0.5 h	0.02 pmol/L Standard Deviation 5.32	-0.79 pmol/L Standard Deviation 6.77
Change From Time-matched Baseline in Peptide YY3-36 (PYY3-36) Concentration at Day 28 Change at Day 28: 4.5 h	-8.33 pmol/L Standard Deviation 6.73	-2.47 pmol/L Standard Deviation 7.66

SECONDARY outcome

Timeframe: 0.5 (8:00 clock time; prior to standardized breakfast), 2.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 2.5, 4.5 hours post study drug administration on Day 28

Population: PD population.

Change was calculated by subtracting time-matched baseline value from Day 28 value. Baseline value was the Day -1 time-matched obestatin assessment.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Change From Time-matched Baseline in Obestatin Concentration at Day 28 Change at Day 28: 0.5 h	0.04 nmol/L Standard Deviation 0.09	0.02 nmol/L Standard Deviation 0.11
Change From Time-matched Baseline in Obestatin Concentration at Day 28 Change at Day 28: 2.5 h	0.03 nmol/L Standard Deviation 0.09	0.01 nmol/L Standard Deviation 0.11
Change From Time-matched Baseline in Obestatin Concentration at Day 28 Change at Day 28: 4.5 h	-0.01 nmol/L Standard Deviation 0.08	-0.01 nmol/L Standard Deviation 0.12

SECONDARY outcome

Timeframe: 0.5 (8:00 clock time; prior to standardized breakfast), 2.5, 4.5 hours on Day -1 (baseline), 0.5 (prior to standardized breakfast), 2.5, 4.5 hours post study drug administration on Day 28

Population: PD population. Here, 'n' signifies patients with oxyntomodulin assessment at the specified time point.

Percentage of patients with oxyntomodulin level less than or equal to (\<=) limit of detection (LOD), above limit of quantification (LOQ) and between LOD and LOQ were reported. The LOD and LOQ values for oxyntomodulin were 70 and 200 picogram per milliliter (pg/mL) respectively.

Outcome measures

Outcome measures
Measure	Lixisenatide n=75 Participants 1-step initiation regimen of lixisenatide.	Liraglutide n=68 Participants 2-step initiation regimen of liraglutide.
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 0.5 h: <=LOD (n = 75, 68)	33.3 percentage of participants	20.6 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 0.5 h: LOD-LOQ (n = 75, 68)	49.3 percentage of participants	55.9 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 0.5 h: >LOQ (n = 75, 68)	17.3 percentage of participants	23.5 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 2.5 h: <=LOD (n = 75, 68)	12.0 percentage of participants	8.8 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 2.5 h: LOD-LOQ (n = 75, 68)	25.3 percentage of participants	23.5 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 2.5 h: >LOQ (n = 75, 68)	62.7 percentage of participants	67.6 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 4.5 h: <=LOD (n = 75, 68)	17.3 percentage of participants	11.8 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 4.5 h: LOD-LOQ (n = 75, 68)	34.7 percentage of participants	39.7 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day -1, 4.5 h: >LOQ (n = 75, 68)	48.0 percentage of participants	48.5 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 0.5 h: <=LOD (n = 75, 68)	38.7 percentage of participants	30.9 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 0.5 h: LOD-LOQ (n = 75, 68)	40.0 percentage of participants	51.5 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 0.5 h: >LOQ (n = 75, 68)	21.3 percentage of participants	17.6 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 2.5 h: <=LOD (n = 74, 68)	52.7 percentage of participants	16.2 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 2.5 h: LOD-LOQ (n = 74, 68)	32.4 percentage of participants	48.5 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 2.5 h: >LOQ (n = 74, 68)	14.9 percentage of participants	35.3 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 4.5 h: <=LOD (n = 75, 68)	52.0 percentage of participants	20.6 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 4.5 h: LOD-LOQ (n = 75, 68)	33.3 percentage of participants	52.9 percentage of participants
Percentages of Patients by Ranges of Oxyntomodulin Levels Day 28, 4.5 h: >LOQ (n = 75, 68)	14.7 percentage of participants	26.5 percentage of participants

Adverse Events

Lixisenatide

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Liraglutide

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lixisenatide n=77 participants at risk 1-step initiation regimen of lixisenatide.	Liraglutide n=71 participants at risk 2-step initiation regimen of liraglutide.
Infections and infestations Nasopharyngitis	3.9% 3/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	7.0% 5/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	18.2% 14/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	36.6% 26/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	1.3% 1/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	5.6% 4/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	11.7% 9/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	15.5% 11/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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 distension	6.5% 5/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	12.7% 9/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	2.6% 2/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	7.0% 5/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	2.6% 2/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	15.5% 11/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	7.8% 6/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	16.9% 12/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	22.1% 17/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	22.5% 16/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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	10.4% 8/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	7.0% 5/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.
Musculoskeletal and connective tissue disorders Back pain	3.9% 3/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	11.3% 8/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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 Fatigue	6.5% 5/77 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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.	5.6% 4/71 • First dose of study drug up to 3 days after the last dose administration, up to 31 days Median exposure to study treatment was 28 days in both treatment 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