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Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Combination Versus Insulin Glargine Alone on Top of Metformin in Type 2 Diabetic Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01476475
First received: November 4, 2011
Last updated: December 16, 2016
Last verified: December 2016
  Purpose

Primary Objective:

  • The purpose of this study was to compare insulin glargine/ lixisenatide fixed ratio combination (FRC) versus insulin glargine on glycemic control over 24 weeks, as evaluated by glycosylated hemoglobin (HbA1c) reduction in type 2 diabetic participants treated with metformin.

Secondary Objectives:

  • To compare insulin glargine/lixisenatide FRC versus insulin glargine over 24 weeks on:

    • Glycemic control in relation to a meal as evaluated by post-prandial plasma glucose and glucose excursions during a standardized meal test;
    • Percentage of participants reaching HbA1c <7% or ≤6.5%;
    • 7-point Self-Monitored Plasma Glucose (SMPG) profile;
    • Body weight;
    • Insulin glargine dose
    • Fasting Plasma Glucose (FPG);
    • Percentage of participants requiring rescue therapy during the 24-week open label treatment period;
  • To assess safety and tolerability of insulin glargine/lixisenatide FRC.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Insulin glargine /lixisenatide Fixed Ratio Combination
Drug: Insulin glargine
Drug: Metformin (Background drug)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, 24-week, Open-label, 2-arm Parallel-group, Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine on Top of Metformin in Type 2 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change in HbA1c From Baseline to Week 24 [ Time Frame: Baseline, 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 till before the introduction of rescue medication and up to 14 days after the last injection of investigational medicinal product (IMP).


Secondary Outcome Measures:
  • Change in 2-hour Postprandial Plasma Glucose (PPG) From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ]
    The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG 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 till before the introduction of rescue medication and up to the date of last injection of IMP.

  • Change in 2-hour Plasma Glucose Excursion From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ]
    2-hour plasma glucose excursion = 2-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion 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 till before the introduction of rescue medication and up to the date of last injection of IMP.

  • Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profiles From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ]
    Participants recorded a 7-point plasma glucose profile measured before and 2-hours after each meal and at bedtime, over a single day, once in a week before baseline, before visit Week 12 and before visit Week 24 and the average value across the profiles performed in the week before 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. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to the date of last injection of IMP.

  • Change in Body Weight From Baseline to Week 24 [ Time Frame: Baseline, 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 till before the introduction of rescue medication and up to 3 days after the last injection of IMP.

  • Average Daily Insulin Glargine Dose at Week 24 [ Time Frame: Week 24 ]
    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 till before the introduction of rescue medication and up to the date of last injection of IMP.

  • Change in FPG From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ]
    Change in FPG 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 till before the introduction of rescue medication and up to 1 day after the last injection of IMP.

  • Percentage of Participants Requiring Rescue Therapy During 24-week Treatment Period [ Time Frame: Baseline up to Week 24 ]
    Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceed the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) were performed. Threshold values from Week 8 to Week 12: fasting SMPG/FPG >240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8%.

  • Percentage of Participants With HbA1c ≤6.5 % or <7.0 % at Week 24 [ Time Frame: Week 24 ]
    On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP.

  • Change in 30-minute and 1-hour PPG From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ]
    The 30 minute and 1-hour PPG test measured blood glucose 30 minutes and 1-hour after eating a standardized meal. Change in PPG 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 till before the introduction of rescue medication and up to the date of last injection of IMP.

  • Change in 30 Minute and 1-hour Plasma Glucose Excursion From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ]
    30-minute and 1-hour plasma glucose excursion = 30-minute and 1-hour PPG minus plasma glucose value obtained 30 minutes prior to the start of the meal and before IMP administration. Change in plasma glucose excursion 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 till before the introduction of rescue medication and up to the date of last injection of IMP.

  • Percentage of Participants Reaching HbA1c <7% at Week 24 With no Documented Symptomatic Hypoglycemia During 24-week Treatment Period [ Time Frame: Baseline up to Week 24 ]
    Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L). Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one documented symptomatic hypoglycemia before the introduction of rescue medication and up to 1 day after the last injection of IMP. Otherwise, they were counted as missing data. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug till before the introduction of rescue medication and up to 14 days after the last injection of IMP.

  • Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 [ Time Frame: Week 24 ]
    Participants without any 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 (for HbA1c and body weight) was available and showed non-response. Otherwise, they were counted as missing data.

  • Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia [ Time Frame: First dose of study drug up to 3 days after the last dose administration (maximum of 219 days) ]
    Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤70 mg/dL (3.9 mmol/L).Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes were associated with sufficient neuroglycopenia to induce seizure, unconsciousness or coma. All episodes in which neurological impairment was severe enough to prevent self-treatment and which were thought to place participants at risk for injury to themselves or others.


Enrollment: 323
Study Start Date: November 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin glargine/Lixisenatide Fixed Ratio Combination (FRC)
FRC injected once daily (QD) for 24 weeks. Dose individually adjusted.
Drug: Insulin glargine /lixisenatide Fixed Ratio Combination
FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using pen-type injector (Tactipen®): 100 U/ml insulin glargine and 50 mcg Lixisenatide (ratio of 2 U/1 mcg). The initial dose was 10 U/5 mcg and then dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L.
Other Name: (HOE901/AVE0010)
Drug: Metformin (Background drug)
Pharmaceutical form: Tablet; Route of administration: oral administration. To be kept at stable dose (≥1.5 g/day) throughout the study.
Active Comparator: Insulin glargine
Insulin glargine QD for 24 weeks. Dose individually adjusted.
Drug: Insulin glargine
Insulin glargine (100 U/ml) was self-administered by SC injection before breakfast using pen-type injector (Lantus® Solostar®). The initial daily dose of insulin glargine was 10 U and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L).
Other Name: Lantus
Drug: Metformin (Background drug)
Pharmaceutical form: Tablet; Route of administration: oral administration. To be kept at stable dose (≥1.5 g/day) throughout the study.

Detailed Description:
Approximately 27 weeks including a 24-week treatment period.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

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

Exclusion criteria:

  • Age < legal age of adulthood (18 years).
  • Screening HbA1c <7% or >10%.
  • Screening FPG >250 mg/dL (>13.9 mmol/L).
  • Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
  • Type 1 diabetes mellitus.
  • Treatment with glucose-lowering agent(s) other than metformin in a period of 3 months prior to screening.
  • Use of insulin within the last 6 months.
  • Previous use of insulin, except for episode(s) of short-term treatment (≤15 consecutive days) due to intercurrent illness.
  • Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN) at screening.
  • Calcitonin ≥20 pg/ml (5.9 pmol/l) at screening.
  • Alanine Transferase (ALT) >3 ULN 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).
  • Uncontrolled or inadequately controlled hypertension at the time of screening with a resting supine systolic or diastolic blood pressure >180 mmHg or >110 mmHg, respectively.
  • Within the last 6 months prior to screening: history of heart failure requiring hospitalization, myocardial infarction, or stroke. Planned coronary, carotid or peripheral artery revascularisation procedures.
  • Body Mass Index (BMI) ≤20 or >40 kg/m^2.
  • Any previous treatment with lixisenatide

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01476475

  Hide Study Locations
Locations
United States, Arkansas
Investigational Site Number 840408
Little Rock, Arkansas, United States, 72205
United States, California
Investigational Site Number 840412
Paramount, California, United States, 90723
United States, Georgia
Investigational Site Number 840401
Larenceville, Georgia, United States, 30045
Investigational Site Number 840417
Roswell, Georgia, United States, 30076
United States, Kentucky
Investigational Site Number 840403
Lexington, Kentucky, United States, 40504
United States, Maryland
Investigational Site Number 840404
Hyattsville, Maryland, United States, 20782
Investigational Site Number 840405
Rockville, Maryland, United States, 20852
United States, Nevada
Investigational Site Number 840411
Las Vegas, Nevada, United States, 89148
United States, New York
Investigational Site Number 840415
West Seneca, New York, United States, 14224
United States, Oklahoma
Investigational Site Number 840402
Norman, Oklahoma, United States, 73069
United States, Oregon
Investigational Site Number 840407
Medford, Oregon, United States, 97504
United States, Pennsylvania
Investigational Site Number 840413
Durham, Pennsylvania, United States, 27713
United States, Texas
Investigational Site Number 840410
Dallas, Texas, United States, 75230
United States, Washington
Investigational Site Number 840414
Renton, Washington, United States, 98055
Chile
Investigational Site Number 152404
Santiago, Chile, 7500347
Investigational Site Number 152405
Santiago, Chile, 7500347
Investigational Site Number 152403
Santiago, Chile, 7500710
Investigational Site Number 152401
Santiago, Chile, 7980378
Investigational Site Number 152402
Santiago, Chile, 8320000
Czech Republic
Investigational Site Number 203403
Novy Jicin, Czech Republic, 74101
Investigational Site Number 203401
Plzen, Czech Republic, 32600
Investigational Site Number 203402
Praha 2, Czech Republic, 12808
Investigational Site Number 203405
Praha 8, Czech Republic, 18100
Denmark
Investigational Site Number 208401
København Nv, Denmark, 2400
Investigational Site Number 208404
Køge, Denmark, 4600
Investigational Site Number 208402
Slagelse, Denmark, 4200
Investigational Site Number 208403
Svendborg, Denmark, 5700
France
Investigational Site Number 250402
Narbonne, France, 11018
Investigational Site Number 250404
Poitiers Cedex, France, 86021
Investigational Site Number 250401
Vandoeuvre Les Nancy, France, 54511
Germany
Investigational Site Number 276401
Dresden, Germany, 01307
Investigational Site Number 276402
Ludwigshafen, Germany, 67059
Investigational Site Number 276403
Oberhausen, Germany, 46045
Hungary
Investigational Site Number 348401
Balatonfüred, Hungary, 8230
Investigational Site Number 348405
Budapest, Hungary, 1041
Investigational Site Number 348406
Budapest, Hungary, 1212
Investigational Site Number 348404
Debrecen, Hungary, 4043
Investigational Site Number 348402
Szeged, Hungary, 6720
Investigational Site Number 348403
Szeged, Hungary, 6722
Lithuania
Investigational Site Number 440401
Kaunas, Lithuania, LT-49456
Investigational Site Number 440402
Kaunas, Lithuania, LT-51270
Investigational Site Number 440403
Kedainiai, Lithuania, LT-57164
Investigational Site Number 440404
Klaipeda, Lithuania, LT-92304
Mexico
Investigational Site Number 484404
Acapulco, Mexico, 39670
Investigational Site Number 484401
Cuernavaca, Mexico, 62250
Investigational Site Number 484405
Durango, Mexico, 34270
Investigational Site Number 484402
Guadalajara, Mexico, 44210
Investigational Site Number 484403
Guadalajara, Mexico, 44656
Poland
Investigational Site Number 616405
Bialystok, Poland, 15-435
Investigational Site Number 616406
Gdansk, Poland, 80-847
Investigational Site Number 616403
Krakow, Poland, 31-548
Investigational Site Number 616407
Lodz, Poland, 94-074
Investigational Site Number 616404
Pulawy, Poland, 24-100
Investigational Site Number 616402
Szczecin, Poland, 70-506
Investigational Site Number 616401
Warszawa, Poland, 02-507
Romania
Investigational Site Number 642402
Brasov, Romania, 500365
Investigational Site Number 642403
Bucuresti, Romania, 020475
Investigational Site Number 642405
Iasi, Romania, 700547
Investigational Site Number 642401
Oradea, Romania, 410169
Investigational Site Number 642406
Targu Mures, Romania, 540142
Investigational Site Number 642404
Timisoara, Romania, 300133
Slovakia
Investigational Site Number 703402
Bratislava, Slovakia, 85101
Investigational Site Number 703403
Kosice, Slovakia, 04001
Investigational Site Number 703406
Kosice, Slovakia, 04013
Investigational Site Number 703404
Moldava Nad Bodvou, Slovakia, 04525
Investigational Site Number 703405
Nitra, Slovakia, 94911
Investigational Site Number 703401
Zilina, Slovakia, 01001
Sweden
Investigational Site Number 752402
Skellefteå, Sweden, 931 32
Investigational Site Number 752401
Stockholm, Sweden, 171 76
Investigational Site Number 752403
Växjö, Sweden, 351 85
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Additional Information:
Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01476475     History of Changes
Other Study ID Numbers: ACT12374
2011-002090-36 ( EudraCT Number )
U1111-1121-7111 ( Other Identifier: UTN )
Study First Received: November 4, 2011
Results First Received: December 16, 2016
Last Updated: December 16, 2016

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Metformin
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017