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

A 24-week, Open-label, Randomized, 2-arm Parallel Group, Multinational, Multi-center Clinical Trial to Compare the Efficacy and Safety of Lixisenatide Injected Prior to the Main Meal of the Day Versus Lixisenatide Injected Prior to Breakfast in Type 2 Diabetic Patients Not Adequately Controlled on Metformin

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Lixisenatide (AVE0010); Device: Self-injector pen device (OptiClik®); Drug: Metformin

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 451
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Brampton, Canada, L6R 3J5
    • Investigational Site Number 124102
  • Coquitlam, Canada, V3K 3P4
    • Investigational Site Number 124108
  • Etobicoke, Canada, M9R 4E1
    • Investigational Site Number 124106
  • Kelowna, Canada, V1Y 1Z9
    • Investigational Site Number 124113
  • Laval, Canada, H7T 2P5
    • Investigational Site Number 124110
  • Newmarket, Canada, L3Y 5G8
    • Investigational Site Number 124103
  • Oakville, Canada, L6H 3P1
    • Investigational Site Number 124101
  • St-Romuald, Canada, G6W 5M6
    • Investigational Site Number 124111
  • Thornhill, Canada, L4J 8L7
    • Investigational Site Number 124104
  • Toronto, Canada, M9V 4B4
    • Investigational Site Number 124105
  • Vancouver, Canada, V5Z 1M9
    • Investigational Site Number 124112
• Czech Republic
  • Plzen, Czech Republic, 32600
    • Investigational Site Number 203104
  • Praha 10, Czech Republic, 10000
    • Investigational Site Number 203102
  • Praha 10, Czech Republic, 10034
    • Investigational Site Number 203101
  • Praha 2, Czech Republic, 12808
    • Investigational Site Number 203105
  • Trutnov, Czech Republic, 54101
    • Investigational Site Number 203103
  • Ujezd U Brna, Czech Republic, 664 53
    • Investigational Site Number 203106
• France
  • Clermont Ferrand, France, 63000
    • Investigational Site Number 250108
  • Menton, France, 06500
    • Investigational Site Number 250102
  • Nanterre, France, 92014
    • Investigational Site Number 250103
  • Rennes, France, 35700
    • Investigational Site Number 250105
• Germany
  • Asslar, Germany, 35614
    • Investigational Site Number 276103
  • Bad Mergentheim, Germany, 97980
    • Investigational Site Number 276102
  • Berlin, Germany, 13125
    • Investigational Site Number 276107
  • Heidelberg, Germany, 69115
    • Investigational Site Number 276101
  • Künzing, Germany, 94550
    • Investigational Site Number 276104
  • Pirna, Germany, 01796
    • Investigational Site Number 276105
  • St. Ingbert-Oberwürzbach, Germany, 66386
    • Investigational Site Number 276108
• Poland
  • Bytom, Poland, 41-902
    • Investigational Site Number 616106
  • Gdansk, Poland, 80-858
    • Investigational Site Number 616102
  • Krakow, Poland, 31-450
    • Investigational Site Number 616101
  • Lublin, Poland, 20-538
    • Investigational Site Number 616103
  • Oswiecim, Poland, 32-600
    • Investigational Site Number 616108
  • Wroclaw, Poland, 50-127
    • Investigational Site Number 616105
  • Wroclaw, Poland, 50-306
    • Investigational Site Number 616104
  • Wroclaw, Poland, 50-403
    • Investigational Site Number 616107
• Romania
  • Bucuresti, Romania, 050538
    • Investigational Site Number 642101
  • Oradea, Romania, 410169
    • Investigational Site Number 642105
  • Ploiesti, Romania, 100097
    • Investigational Site Number 642102
  • Resita, Romania, 320076
    • Investigational Site Number 642104
  • Timisoara, Romania, 300456
    • Investigational Site Number 642103
• Russian Federation
  • Moscow, Russian Federation, 119435
    • Investigational Site Number 643103
  • Moscow, Russian Federation, 125367
    • Investigational Site Number 643101
  • Nizhny Novgorod, Russian Federation, 603018
    • Investigational Site Number 643106
  • Samara, Russian Federation, 443067
    • Investigational Site Number 643102
  • St-Petersburg, Russian Federation, 194291
    • Investigational Site Number 643107
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643105
  • St-Petersburg, Russian Federation, 195257
    • Investigational Site Number 643110
  • Vladimir, Russian Federation, 600023
    • Investigational Site Number 643108
  • Voronezh, Russian Federation, 394018
    • Investigational Site Number 643104
• Spain
  • Barcelona, Spain, 08020
    • Investigational Site Number 724104
  • Barcelona, Spain, 08041
    • Investigational Site Number 724103
  • El Ferrol, Spain, 15403
    • Investigational Site Number 724102
  • Hostalets De Balenyà, Spain, 08550
    • Investigational Site Number 724101
  • La Coruña, Spain, 15006
    • Investigational Site Number 724107
  • Málaga, Spain, 29010
    • Investigational Site Number 724106
  • Segovia, Spain, 40002
    • Investigational Site Number 724108
  • Sevilla, Spain, 41014
    • Investigational Site Number 724105
• Ukraine
  • Kharkiv, Ukraine, 61002
    • Investigational Site Number 804108
  • Kharkov, Ukraine, 61022
    • Investigational Site Number 804105
  • Kiev, Ukraine, 2091
    • Investigational Site Number 804102
  • Kyiv, Ukraine, 04114
    • Investigational Site Number 804103
  • Mykolaiv, Ukraine, 54003
    • Investigational Site Number 804104
  • Poltava, Ukraine, 36011
    • Investigational Site Number 804106
  • Zaporozhie, Ukraine, 69600
    • Investigational Site Number 804101
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Investigational Site Number 840112
    • Mesa, Arizona, United States, 85213
      • Investigational Site Number 840113
    • Phoenix, Arizona, United States, 85028
      • Investigational Site Number 840105
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840102
    • Tempe, Arizona, United States
      • Investigational Site Number 840107
  • California
    • Mission Viejo, California, United States, 92691
      • Investigational Site Number 840116
    • Northridge, California, United States, 91325
      • Investigational Site Number 840103
    • Redlands, California, United States, 92374
      • Investigational Site Number 840118
    • Temecula, California, United States, 92591
      • Investigational Site Number 840104
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Investigational Site Number 840122
    • Chicago, Illinois, United States, 60616
      • Investigational Site Number 840119
    • Springfield, Illinois, United States, 62704
      • Investigational Site Number 840114
  • Michigan
    • Flint, Michigan, United States, 48504
      • Investigational Site Number 840120
  • Montana
    • Billings, Montana, United States, 59103
      • Investigational Site Number 840115
  • New Jersey
    • Sea Girt, New Jersey, United States, 08750
      • Investigational Site Number 840101
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Investigational Site Number 840111
  • Utah
    • West Jordan, Utah, United States, 84088
      • Investigational Site Number 840110

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Participants with type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit
• Metformin treatment at a stable dose of at least 1.5 g/day for at least 3 months prior to screening visit.

Exclusion criteria:

• Screening HbA1c < 7.0% and > 10.0%
• Fasting plasma glucose at screening > 250 mg/dL (> 13.9 mmol/L)
• Treatment with glucose-lowering agent(s) other than metformin in a period of 3 months prior to screening, previous use of insulin
• Participants who usually did not eat breakfast
• Type 1 diabetes mellitus
• Body Mass Index (BMI) ≤ 20 kg/m^2 and > 40 kg/m^2
• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method
• Amylase and/or lipase > 3 times the upper limit of the normal laboratory range ( ULN) at screening
• Alanine aminotransferase (ALT) > 3 ULN at screening
• Calcitonin ≧ 20 pg/ml (5.9 pmol/L) at screening
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes)
• Any contra-indication related to metformin
• Any previous treatment with lixisenatide

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lixisenatide Main Meal; 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.	Drug: Lixisenatide (AVE0010); Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous; Device: Self-injector pen device (OptiClik®); Drug: Metformin; To be kept at stable dose (≥1.5 g/day) throughout the study.; Other Names: Route of administration: Oral
Active Comparator: Lixisenatide Breakfast; 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.	Drug: Lixisenatide (AVE0010); Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous; Device: Self-injector pen device (OptiClik®); Drug: Metformin; To be kept at stable dose (≥1.5 g/day) throughout the study.; Other Names: Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c From Baseline to 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.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HbA1c Level <7 % or ≤6.5% at Week 24	Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.	Week 24
Change in Average 7-point SMPG Profiles From Baseline to 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.	Baseline, Week 24
Change in FPG From Baseline to 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.	Baseline, Week 24
Change in Body Weight From Baseline to 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.	Baseline, Week 24
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 Period	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.	Week 24
Percentage of Participants Who Reached the Target of HbA1c <7% And Had No Body Weight Gain at Week 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.	Week 24
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 Period	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.	Week 24
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 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.	Week 24
Change in Diabetes Treatment Satisfaction Questionnaire Score (DTSQs) From Baseline to 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.	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Ahren B, Vorokhobina N, Souhami E, Demil N, Ye J, Aronson R. Equal improvement in glycaemia with lixisenatide given before breakfast or the main meal of the day. J Diabetes Complications. 2014 Sep-Oct;28(5):735-41. doi: 10.1016/j.jdiacomp.2014.05.012. Epub 2014 Jun 5.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: January 16, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (Estimate): January 25, 2012

Study Record Updates

• Last Update Posted (Estimate): October 14, 2016
• Last Update Submitted That Met QC Criteria: August 22, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Lixisenatide
• Other Study ID Numbers: EFC12261; 2011-002416-85 (EudraCT Number); U1111-1118-0841 (Other Identifier: UTN)