Clinical Trial Results:
An open-label, randomized, three-parallel-group study on pharmacodynamic effects of 8-week QD treatment with lixisenatide compared to liraglutide in patients with type 2 diabetes not adequately controlled with insulin glargine with or without metformin
Summary
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EudraCT number |
2012-000027-40 |
Trial protocol |
DE |
Global end of trial date |
25 Jul 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Apr 2016
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First version publication date |
26 Mar 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PDY12625
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01596504 | ||
WHO universal trial number (UTN) |
U1111-1124-1364 | ||
Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-us@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-us@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Aug 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Jul 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate the effects of repeated subcutaneous (SC) doses of lixisenatide 20 microgram (mcg) once daily (QD) as compared to liraglutide 1.2 milligram (mg) QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucose concentration- time curve (AUC) after a standardized breakfast at the end of an 8- week treatment period in subjects with type 2 diabetes mellitus (T2DM) not adequately controlled with insulin glargine (+/- metformin).
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Protection of trial subjects |
Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency.
Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 May 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 142
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Worldwide total number of subjects |
142
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EEA total number of subjects |
142
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
86
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From 65 to 84 years |
56
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 8 centres in Germany between 22 May 2012 to 25 July 2013. | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 236 subjects were screened and 142 subjects were randomized and treated. | ||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Lixisenatide 20 mcg | ||||||||||||||||||||||||||||
Arm description |
Lixisenatide for 8 weeks (up to Day 57) and a maintenance dose of 20 mcg QD. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Lixisenatide
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Investigational medicinal product code |
AVE0010
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Lixisenatide 10 mcg QD for 2 weeks followed by 20 mcg QD for 6 weeks (up to Day 57), to be self-administered with a pen-like injector (OptiClik®), under fasted conditions.
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Arm title
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Liraglutide 1.2 mg | ||||||||||||||||||||||||||||
Arm description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.2 mg QD. | ||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Liraglutide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks (up to Day 57), to be self-administered using a prefilled pen (Victoza®), under fasted conditions.
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Arm title
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Liraglutide 1.8 mg | ||||||||||||||||||||||||||||
Arm description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.8 mg QD. | ||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Liraglutide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 1 week and then 1.8 QD mg for 6 weeks (up to Day 57), to be self-administered by using a prefilled pen (Victoza®) under fasted conditions.
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Baseline characteristics reporting groups
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Reporting group title |
Lixisenatide 20 mcg
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Reporting group description |
Lixisenatide for 8 weeks (up to Day 57) and a maintenance dose of 20 mcg QD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liraglutide 1.2 mg
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Reporting group description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.2 mg QD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liraglutide 1.8 mg
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Reporting group description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.8 mg QD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lixisenatide 20 mcg
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Reporting group description |
Lixisenatide for 8 weeks (up to Day 57) and a maintenance dose of 20 mcg QD. | ||
Reporting group title |
Liraglutide 1.2 mg
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Reporting group description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.2 mg QD. | ||
Reporting group title |
Liraglutide 1.8 mg
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Reporting group description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.8 mg QD. |
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End point title |
Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours | ||||||||||||||||
End point description |
Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 milligram per decilitre (mg/dL) with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration [time: 0.5 hours]) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours). Analysis was carried out on pharmacodynamic (PD) population defined as all randomized subjects, who received at least one dose of lixisenatide 20 microgram (mcg), liraglutide 1.2 milligram (mg) or liraglutide 1.8 mg, and had both a baseline assessment and at least one post-baseline assessment of any primary or secondary PD variables.
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End point type |
Primary
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End point timeframe |
0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 56
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Statistical analysis title |
Lixisenatide vs Liraglutide 1.2 mg | ||||||||||||||||
Statistical analysis description |
Analysis was performed using linear fixed effects model with treatment and stratification factors (HbA1c levels on Day -7 [<8% and >=8%], use of metformin at screening [yes or no]) and the study site as fixed effects and baseline plasma glucose AUC from 0.5 to 4.5 hours as covariate.
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Comparison groups |
Lixisenatide 20 mcg v Liraglutide 1.2 mg
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Number of subjects included in analysis |
89
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||
Method |
Linear fixed effects model | ||||||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||||||
Point estimate |
-6.01
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
1-sided
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lower limit |
-7.77 | ||||||||||||||||
upper limit |
- | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.06
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Notes [1] - To address multiplicity issue and ensure overall 1-sided level of 5%, Hochberg method was used for testing procedure of comparison between lixisenatide vs liraglutide 1.2 mg or 1.8 mg. p-values were ordered (p1<=p2) and following rules were applied: 1)if p2<=0.05: lixisenatide was superior to liraglutide (both dose) 2)if p2>0.05 and p1<=0.025: lixisenatide was superior to dose of liraglutide associated with p1 3)if p2>0.05 and p1>0.025: no comparison was declared as statistically significant. |
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Statistical analysis title |
Lixisenatide vs Liraglutide 1. 8 mg | ||||||||||||||||
Statistical analysis description |
Analysis was performed using linear mixed effects model with treatment and stratification factors (HbA1c levels on Day -7 [<8% and >=8%], use of metformin at screening [yes or no]), and the study site as fixed effects and baseline plasma glucose AUC from 0.5 to 4.5 hours as covariate.
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Comparison groups |
Lixisenatide 20 mcg v Liraglutide 1.8 mg
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
superiority [2] | ||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||
Method |
Linear fixed effects model | ||||||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||||||
Point estimate |
-4.61
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
1-sided
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lower limit |
-6.34 | ||||||||||||||||
upper limit |
- | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.04
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Notes [2] - To address multiplicity issue and ensure overall 1-sided level of 5%, Hochberg method was used for testing procedure of comparison between lixisenatide vs liraglutide 1.2 mg or 1.8 mg. p-values were ordered (p1<=p2) and following rules were applied: 1)if p2<=0.05: lixisenatide was superior to liraglutide (both dose) 2)if p2>0.05 and p1<=0.025: lixisenatide was superior to dose of liraglutide associated with p1 3)if p2>0.05 and p1>0.025: no comparison was declared as statistically significant. |
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End point title |
Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours | ||||||||||||||||
End point description |
Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration [time: 0.5 hours]) to 5 hours after breakfast start (time: 5.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours). Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56
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No statistical analyses for this end point |
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End point title |
Number of Subjects With 2-Hour Postprandial Plasma Glucose <7.77 Millimole Per Litre (mmol/L) at Day 56 | ||||||||||||||||
End point description |
Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. The 2-hour PPG test measured blood glucose 2 hours after start of a standardized breakfast. Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
Day 56
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 56 in Postprandial Plasma Glucose (PPG) Excursion | ||||||||||||||||
End point description |
Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. PPG excursion was determined on Day -3 (Baseline) and Day 56 as the maximum change in PPG from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration. Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 56 in Fasting Plasma Glucose (FPG) | ||||||||||||||||
End point description |
Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3-1000 mg/dL with 1 mg/dL as LOD. The value of FPG on Day -3 was the baseline. Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on Day 56
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 56 in Average 7-Point Self-Monitored Plasma Glucose (SMPG) | ||||||||||||||||
End point description |
Seven-point SMPG (before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime) was measured using Freestyle Precision glucometer and average of the 7 measurements was calculated. Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
Before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime on Day -3 (Baseline) and on Day 56.
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 56 in Corrected C-Peptide AUC From Time 0.5 Hours to 5.5 Hours | ||||||||||||||||
End point description |
C-peptide was assessed using the Electro Chemiluminescence Immuno Assay.The range of the method was 0.2 to 25 nanogram per millilitre (ng/mL) and the LOD was 0.07 ng/mL. Measurement was done on Day -3 (Baseline) and Day 56 as the maximum change in C-peptide from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration. Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours | ||||||||||||||||
End point description |
Glucagon was assessed using the radioimmunoassay. The range of the method was 4.7 to 150 picomole per litre (pmol/L). Measurement was done on Day -3 (Baseline) and Day 56 as the maximum change in Glucagon from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration. Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
0.5 (8:00 clock time, prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 56 in HbA1C | ||||||||||||||||
End point description |
HbA1C was assessed using the high-performance liquid chromatography method. Analysis was carried out on PD population
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End point type |
Secondary
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End point timeframe |
Pre-dose (Hour 0) on Day 1 (Baseline) and Day 56
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 56 in Average Daily Insulin Glargine Dose | ||||||||||||||||
End point description |
Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
Day -7 (Baseline), Day 56
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No statistical analyses for this end point |
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End point title |
Change From Baseline to Day 55 in Gastric Emptying Half Life (t1/2) | ||||||||||||||||
End point description |
Gastric emptying was measured using 13C-octanoic acid breath test by isotope-selective non-dispersive infrared spectrometry. Analysis was carried out on PD population.
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End point type |
Secondary
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End point timeframe |
0 (7:30 clock time, prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55
|
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|
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No statistical analyses for this end point |
|
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End point title |
Change From Baseline to Day 55 in Gastric Emptying Coefficient | ||||||||||||||||
End point description |
Gastric emptying was measured using 13C-octanoic acid breath test by isotope-selective non-dispersive infrared spectrometry. Gastric emptying coefficient was derived from a mathematical formula that describes the gastric-emptying rate and gives an overall index of gastric emptying. Analysis was carried out on PD population.
|
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End point type |
Secondary
|
||||||||||||||||
End point timeframe |
0 (7:30 clock time, prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55
|
||||||||||||||||
|
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No statistical analyses for this end point |
|
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End point title |
Change From Baseline to Day 57/58 in 24-Hour Mean Heart Rate | ||||||||||||||||
End point description |
The baseline value was the 24-hour mean on Day -2/-1 determined as overall, night- and day-time mean. Measurements were made every 15 minutes from 07:00 to 23:00 (daytime) and every 30 minutes from 23:00 to 07:00 (nighttime) at baseline and Day 57/58. Measurements were obtained after 10 minutes in the supine resting position. Analysis was carried out on PD population.
|
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End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Every 15 minutes from 07:00 clock time to 23:00 clock time (daytime) and every 30 minutes from 23:00 clock time to 07:00 clock time (nighttime) on Day -2/-1 (Baseline) and Day 57/58
|
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|
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No statistical analyses for this end point |
|
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End point title |
Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure | ||||||||||||||||||||||||
End point description |
The baseline value was the 24-hour means on Day -2/-1 determined as overall, night- and day-time mean. Measurements were made every 15 minutes from 07:00 to 23:00 (day time) and every 30 minutes from 23:00 to 07:00 (night time) at baseline and at Day 57/58. Measurements were obtained after 10 minutes in the supine resting position. Analysis was carried out on PD population.
|
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End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Every 15 minutes from 07:00 clock time to 23:00 clock time (daytime) and every 30 minutes from 23:00 clock time to 07:00 clock time (nighttime) on Day -2/-1 (Baseline) and Day 57/58
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
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End point title |
Change From Baseline to Day 57 in Body Weight | ||||||||||||||||
End point description |
Analysis was carried out on PD population.
|
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End point type |
Secondary
|
||||||||||||||||
End point timeframe |
0.5 hours prior to standardized breakfast (7:30 clock time) on Day -1 (Baseline); 0.5 hours prior to study drug administration on Day 57
|
||||||||||||||||
|
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No statistical analyses for this end point |
|
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End point title |
Change From Baseline to Day 57 in Waist Circumference | ||||||||||||||||
End point description |
Analysis was carried out on PD population.
|
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End point type |
Secondary
|
||||||||||||||||
End point timeframe |
0.5 hours prior to standardized breakfast (7:30 clock time) on Day -1 (Baseline); 0.5 hours prior to IMP administration on Day 57
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Change From Baseline to Day 56 in The Cumulative Score Mean on The Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast | ||||||||||||||||||||||||||||||||
End point description |
Visual Analogue Scale, 100 millimetre (mm) in length with words anchored at each end, expressing the most positive and the most negative rating, was used to assess hunger, satiety, fullness and prospective food consumption. Analysis was carried out on PD population.
|
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End point type |
Secondary
|
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End point timeframe |
0.5 (8:00 clock time, prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours on Day -3; 0 (prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56
|
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|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
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Adverse events information
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Timeframe for reporting adverse events |
All Adverse Events (AE) were collected from signature of the informed consent form up to the end of study regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported adverse events are treatment-emergent adverse events that developed/worsened during the ‘on treatment period’ (the time from the first drug injection [included] up to 3 days after the last injection of drug administration [included]).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Lixisenatide 20 mcg
|
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Reporting group description |
Lixisenatide for 8 weeks (up to Day 57) and a maintenance dose of 20 mcg QD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liraglutide 1.2 mg
|
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Reporting group description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.2 mg QD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liraglutide 1.8 mg
|
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Reporting group description |
Liraglutide for 8 weeks (up to Day 57) and a maintenance dose of 1.8 mg QD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
25 Sep 2012 |
- Change in the Inclusion/Exclusion criteria: Subjects were eligible to enter in the screening phase with a stable dose of Neutral Protamine Hagedorn (NPH) or insulin glargine of at least 10 International units per day (IU/Day) (for at least 2 months prior to screening) instead of 20 units per day, alone or combined with a stable dose of metformin with or without Dipeptidyl peptidase (DPP)-IV inhibitor or sulfonylurea. Subjects receiving NPH or insulin glargine with metformin combined with DPP-IV inhibitors or sulfonylurea were eligible to enter in the screening phase provided that the run-in period will last 12 fixed weeks and subjects who received liraglutide 3 months prior to the time of screening were eligible. Inclusion of subjects who had received liraglutide provided that liraglutide treatment was stopped at least 3 months before the time of the screening for other reason than safety/tolerability issue or lack of efficacy.
- Change in the run-in period: Either the run-in period was to be extended up to 12 weeks, if needed, in subjects treated with an initial therapy with NPH or insulin glargine of at least 10 IU/Day with or without metformin alone; or the run-in period was to be fixed to 12 weeks for subjects treated with an initial therapy with NPH or insulin glargine with metformin combined with DPP-4 inhibitor or sulfonylurea. This period was needed for reaching an appropriate baseline glycemic control after stopping DPP-4 inhibitor or sulfonylurea.
- Change in the study/period flow charts and duration of participation: The changes in the run-in period with additional visits was to be included in the change in the study/period flow charts. The maximum duration of participation per subject was 23 weeks and one day +/- 2 days. Reporting timelines of SAE by the investigator have been changed from "within 1 working day" to "within 24 hours" following the European Commission (EC) guidance 2011/C 172/01 (dated 11 June 2011). |
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Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |