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Comparison of Lixisenatide Injected Prior to the Main Meal of the Day Versus Prior to Breakfast in Type 2 Diabetic Patients on Metformin

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Drug: Lixisenatide (AVE0010)
Device: Self-injector pen device (OptiClik®)
Drug: Metformin
Registration Number
NCT01517412
Lead Sponsor
Sanofi
Brief Summary

Primary Objective:

- To compare the two treatment regimens in terms of change of glycosylated hemoglobin (HbA1c) from baseline to endpoint (Week 24)

Secondary Objective:

* To assess the effect of the 2 lixisenatide regimens on:

* The percentage of participants who reached the target of HbA1c \< 7% or ≤ 6.5% at Week 24

* Fasting Plasma Glucose (FPG)

* 7-point Self-Monitored Plasma Glucose (SMPG) profiles

* Body weight

* To assess the safety and tolerability of the 2 lixisenatide regimens

Detailed Description

The maximum study duration was 28 weeks per participant, including a 24-week randomized treatment period.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
451
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Lixisenatide BreakfastSelf-injector pen device (OptiClik®)Lixisenatide 10 mcg QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24.
Lixisenatide Main MealSelf-injector pen device (OptiClik®)Lixisenatide 10 mcg once daily (QD) within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24.
Lixisenatide Main MealMetforminLixisenatide 10 mcg once daily (QD) within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24.
Lixisenatide Main MealLixisenatide (AVE0010)Lixisenatide 10 mcg once daily (QD) within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24.
Lixisenatide BreakfastLixisenatide (AVE0010)Lixisenatide 10 mcg QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24.
Lixisenatide BreakfastMetforminLixisenatide 10 mcg QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24.
Primary Outcome Measures
NameTimeMethod
Change in HbA1c From Baseline to Week 24Baseline, Week 24

Change in HbA1C was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With HbA1c Level <7 % or ≤6.5% at Week 24Week 24

Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.

Change in Average 7-point SMPG Profiles From Baseline to Week 24Baseline, Week 24

Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime two times in a week before baseline, before visit Week 8, before visit Week 12 and before visit week 24. The average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline 7-point SMPG assessment during on-treatment period.

Percentage of Participants Who Reached the Target of HbA1c <7% at Week 24 And Did Not Experience Confirmed Symptomatic Hypoglycemia (Plasma Glucose [PG] <60 mg/dL [3.3 mmol/L]) During 24-Week Treatment PeriodWeek 24

Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemic episode with an accompanying PG\<60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate if no PG measurement was available. On-treatment period for symptomatic hypoglycemia assessment was defined as time from first dose of study drug up to 1 day after last dose of study drug. Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one symptomatic hypoglycemia. Otherwise, they were counted as missing.

Change in FPG From Baseline to Week 24Baseline, Week 24

Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline FPG assessment during on-treatment period.

Change in Body Weight From Baseline to Week 24Baseline, Week 24

Change in body weight was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during on-treatment period.

Percentage of Participants Who Reached the Target of HbA1c <7% And Had No Body Weight Gain at Week 24Week 24

Participants without post-baseline on-treatment values for (HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed no response. Otherwise, they were counted as missing.

Percentage of Participants Who Reached the Target of HbA1c <7% And Had No Body Weight Gain at Week 24 And Did Not Experience Confirmed Symptomatic Hypoglycemia (PG<60 mg/dL [3.3 mmol/L]) During the 24-Week Treatment PeriodWeek 24

Participants without post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart not more than 30-days apart were counted as non-responders if at least one of components (HbA1c and/or body weight) was available and showed no response. Otherwise, they were counted as missing.

Percentage of Participants Who Reached the Target of HbA1c <7% And Had a 2-hour Postprandial Plasma Glucose (PPG) <140mg/dL After Breakfast or Main Meal At Week 24Week 24

On-treatment period for 2-hour PPG assessment was defined as the time from the first dose of study drug up to the day of last dose of study drug. Participants without post-baseline on-treatment values (for HbA1c and 2-hour PPG) that were no more than 30-days apart were counted as non-responders if at least one of the components (HbA1cand/or 2-hour PPG) was available and showed no response. Otherwise, they were counted as missing.

Change in Diabetes Treatment Satisfaction Questionnaire Score (DTSQs) From Baseline to Week 24Baseline, Week 24

DTSQ is a validated measure to assess how satisfied participants with diabetes are with their treatment and how they perceive hyper- and hypoglycemia. It consists of 8 questions which are answered on a Likert scale from 0 to 6. DTSQ treatment satisfaction score is the sum of question 1, 4, 5, 6, 7 and 8 scores and ranges between 0 and 36, where higher scores indicate more treatment satisfaction. On-treatment period for treatment satisfaction assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. Missing data was imputed using LOCF. Here, number of participants analyzed = participants with both baseline and Week 24 DTSQ score assessment during on-treatment period.

Trial Locations

Locations (82)

Investigational Site Number 203104

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Plzen, Czech Republic

Investigational Site Number 616106

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Bytom, Poland

Investigational Site Number 616105

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Wroclaw, Poland

Investigational Site Number 616104

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Wroclaw, Poland

Investigational Site Number 642101

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Bucuresti, Romania

Investigational Site Number 642105

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Oradea, Romania

Investigational Site Number 642102

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Ploiesti, Romania

Investigational Site Number 642104

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Resita, Romania

Investigational Site Number 642103

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Timisoara, Romania

Investigational Site Number 804106

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Poltava, Ukraine

Investigational Site Number 804101

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Zaporozhie, Ukraine

Investigational Site Number 840102

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Tempe, Arizona, United States

Investigational Site Number 840113

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Mesa, Arizona, United States

Investigational Site Number 840107

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Tempe, Arizona, United States

Investigational Site Number 840122

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Chicago, Illinois, United States

Investigational Site Number 840119

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Chicago, Illinois, United States

Investigational Site Number 840120

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Flint, Michigan, United States

Investigational Site Number 250105

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Rennes, France

Investigational Site Number 276103

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Asslar, Germany

Investigational Site Number 276102

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Bad Mergentheim, Germany

Investigational Site Number 124106

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Etobicoke, Canada

Investigational Site Number 276107

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Berlin, Germany

Investigational Site Number 840116

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Mission Viejo, California, United States

Investigational Site Number 840110

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West Jordan, Utah, United States

Investigational Site Number 840118

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Redlands, California, United States

Investigational Site Number 124102

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Brampton, Canada

Investigational Site Number 840111

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Fargo, North Dakota, United States

Investigational Site Number 124110

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Laval, Canada

Investigational Site Number 840101

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Sea Girt, New Jersey, United States

Investigational Site Number 124108

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Coquitlam, Canada

Investigational Site Number 124113

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Kelowna, Canada

Investigational Site Number 276101

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Heidelberg, Germany

Investigational Site Number 124101

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Oakville, Canada

Investigational Site Number 276108

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St. Ingbert-Oberwürzbach, Germany

Investigational Site Number 124105

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Toronto, Canada

Investigational Site Number 276105

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Pirna, Germany

Investigational Site Number 203105

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Praha 2, Czech Republic

Investigational Site Number 203106

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Ujezd U Brna, Czech Republic

Investigational Site Number 276104

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Künzing, Germany

Investigational Site Number 616108

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Oswiecim, Poland

Investigational Site Number 616107

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Wroclaw, Poland

Investigational Site Number 643103

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Moscow, Russian Federation

Investigational Site Number 724103

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Barcelona, Spain

Investigational Site Number 724104

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Barcelona, Spain

Investigational Site Number 643105

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St-Petersburg, Russian Federation

Investigational Site Number 804102

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Kiev, Ukraine

Investigational Site Number 804104

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Mykolaiv, Ukraine

Investigational Site Number 724102

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El Ferrol, Spain

Investigational Site Number 724107

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La Coruña, Spain

Investigational Site Number 804105

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Kharkov, Ukraine

Investigational Site Number 724106

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Málaga, Spain

Investigational Site Number 804103

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Kyiv, Ukraine

Investigational Site Number 250108

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Clermont Ferrand, France

Investigational Site Number 250102

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Menton, France

Investigational Site Number 250103

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Nanterre, France

Investigational Site Number 124103

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Newmarket, Canada

Investigational Site Number 124111

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St-Romuald, Canada

Investigational Site Number 124104

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Thornhill, Canada

Investigational Site Number 124112

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Vancouver, Canada

Investigational Site Number 840103

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Northridge, California, United States

Investigational Site Number 840104

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Temecula, California, United States

Investigational Site Number 840114

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Springfield, Illinois, United States

Investigational Site Number 616101

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Krakow, Poland

Investigational Site Number 724101

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Hostalets De Balenyà, Spain

Investigational Site Number 724108

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Segovia, Spain

Investigational Site Number 724105

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Sevilla, Spain

Investigational Site Number 804108

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Kharkiv, Ukraine

Investigational Site Number 840105

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Phoenix, Arizona, United States

Investigational Site Number 840115

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Billings, Montana, United States

Investigational Site Number 840112

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Glendale, Arizona, United States

Investigational Site Number 203102

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Praha 10, Czech Republic

Investigational Site Number 203101

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Praha 10, Czech Republic

Investigational Site Number 203103

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Trutnov, Czech Republic

Investigational Site Number 616102

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Gdansk, Poland

Investigational Site Number 616103

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Lublin, Poland

Investigational Site Number 643106

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Nizhny Novgorod, Russian Federation

Investigational Site Number 643102

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Samara, Russian Federation

Investigational Site Number 643107

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St-Petersburg, Russian Federation

Investigational Site Number 643110

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St-Petersburg, Russian Federation

Investigational Site Number 643108

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Vladimir, Russian Federation

Investigational Site Number 643104

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Voronezh, Russian Federation

Investigational Site Number 643101

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Moscow, Russian Federation

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