Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02787551
Other study ID # EFC13794
Secondary ID 2014-004850-32U1
Status Completed
Phase Phase 3
First received
Last updated
Start date July 6, 2016
Est. completion date November 17, 2018

Study information

Verified date March 2022
Source Sanofi
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Primary Objective: To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) versus GLP-1 receptor agonist (GLP-1 RA) in hemoglobin A1c (HbA1c) change. Secondary Objectives: To compare the overall efficacy and safety of the insulin glargine/lixisenatide FRC to GLP-1 RA on top of metformin (with or without pioglitazone, with or without sodium-glucose co-transporter 2 [SGLT2] inhibitor) in participants with type 2 diabetes. To evaluate safety, efficacy and other endpoints of FRC up to the end of the extension period.


Description:

The maximum duration for GLP1-RA participants was approximately 29 weeks: up to 2 week screening period, a 26 week treatment period (either randomized or uncontrolled), and a 3 or 9 day post-treatment safety follow-up period. Maximum duration for FRC participants was approximately 55 weeks: up to 2-week screening period, a 26-week randomized treatment period, a 26-week extension period and a 3-day post-treatment safety follow-up period. All primary and secondary efficacy, safety and other outcome measures were assessed at the end of the extension period.


Recruitment information / eligibility

Status Completed
Enrollment 514
Est. completion date November 17, 2018
Est. primary completion date May 25, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion criteria : - Participants with type 2 diabetes mellitus diagnosed at least 1 year prior to screening visit. - Participants who were treated with one of the following GLP-1 receptor agonists for at least 4 months prior to screening visit 1 (V1), and with stable dose for at least 3 months prior to screening visit (V1): - Liraglutide (Victoza®) 1.8 milligram (mg) QD or 1.2 mg QD, if the 1.8 mg QD dose was not well tolerated according to the Investigator's judgment or - Exenatide (Byetta®) 10 microgram (µg) BID or of 5 µg BID, if 10 µg BID dose was not well tolerated according to the Investigator's judgment in combination with metformin (daily dose greater than equal to [>=] 1500 mg/day or maximum tolerated dose [MTD]), with or without pioglitazone, with or without SGLT2 inhibitor, all at stable dose for at least 3 months prior to screening. or Participants who were treated with stable dose of one of the following GLP-1 receptor agonists for at least 6 months prior to screening visit (V1): - Exenatide extended-release (Bydureon®) 2 mg once weekly (QW), if well tolerated according to Investigator's judgment, - Albiglutide (Tanzeum®) 50 mg QW or 30 mg QW, if 50 mg QW was not well tolerated according to Investigator's judgment, - Dulaglutide (Trulicity®) 1.5 mg QW or 0.75 mg QW, if 1.5 mg QW was not well tolerated according to Investigator's judgment in combination with metformin (daily dose =1500 mg/day or MTD), with or without pioglitazone, with or without SGLT2 inhibitor, all at stable dose for at least 3 months prior to screening; -Signed written informed consent. Exclusion criteria: - At screening visit, age <18. - Screening HbA1c <7% and >9%. - Pregnancy or lactation, women of childbearing potential with no effective contraceptive method. - Any use of antidiabetic drugs within 3 months prior to the screening visit other than those described in the inclusion criteria. - Previous treatment with insulin in the year prior to screening visit (note: short-term treatment with insulin [<=10 days] due to intercurrent illness including gestational diabetes was allowed at the discretion of the study physician). - Laboratory findings at the time of screening, including: - Fasting plasma glucose (FPG) >250 mg/dL (13.9 millimoles per litre [mmol/L]), - Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN), - Alanine transaminase or aspartate transaminase >3 ULN, - Calcitonin >=20 pg/mL (5.9 pmol/L), - Positive pregnancy test. - Participant who had renal function impairment with estimated glomerular filtration rate <30mL/min/1.73m^2 (using the Modification of Diet in Renal Disease formula) or end-stage renal disease. - Contraindication to use of insulin glargine, or lixisenatide or GLP-1 receptor agonist (Victoza®, Byetta®, Bydureon®, Tanzeum® or Trulicity®) according to local labeling. - Any contraindication to metformin or pioglitazone or SGLT2 inhibitor use, according to local labeling. - History of hypersensitivity to insulin glargine, or to any of the excipients. - History of allergic reaction to any GLP-1 receptor agonist or to meta-cresol. - Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia type 2 syndromes). - History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy. - Body mass index <=20 or >40 kg/m^2. Exclusion criteria for the extension period: - Participants in the FRC arm with a rescue therapy and HbA1c >8% at week 22. - Participants in the FRC arm who discontinued prematurely from FRC treatment before week 26. - Participants in the GLP-1 RA treatment arm after randomization. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design


Intervention

Drug:
Insulin glargine/lixisenatide fixed ratio combination
Pharmaceutical form: solution for injection Route of administration: subcutaneous
liraglutide
Pharmaceutical form: solution for injection Route of administration: subcutaneous
exenatide
Pharmaceutical form: solution for injection Route of administration: subcutaneous
exenatide extended-release
Pharmaceutical form: solution for injection Route of administration: subcutaneous
albiglutide
Pharmaceutical form: solution for injection Route of administration: subcutaneous
dulaglutide
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)
Pharmaceutical form: tablet Route of administration: oral If previously taken, doses to remain stable through the study.

Locations

Country Name City State
Canada Investigational Site Number 1240003 Burlington
Canada Investigational Site Number 1240006 Corunna
Canada Investigational Site Number 1240002 Red Deer
Canada Investigational Site Number 1240001 Vancouver
Estonia Investigational Site Number 2330002 Pärnu
Estonia Investigational Site Number 2330001 Tallinn
Estonia Investigational Site Number 2330003 Tallinn
Estonia Investigational Site Number 2330004 Viljandi
Germany Investigational Site Number 2760001 Dresden
Germany Investigational Site Number 2760003 Oldenburg In Holstein
Israel Investigational Site Number 3760001 Haifa
Israel Investigational Site Number 3760002 Haifa
Israel Investigational Site Number 3760005 Jerusalem
Israel Investigational Site Number 3760006 Jerusalem
Israel Investigational Site Number 3760004 Tel Aviv
Italy Investigational Site Number 3800008 Bergamo
Italy Investigational Site Number 3800002 Bologna
Italy Investigational Site Number 3800001 Milano
Italy Investigational Site Number 3800006 Milano
Italy Investigational Site Number 3800005 Napoli
Italy Investigational Site Number 3800003 Roma
Italy Investigational Site Number 3800004 Roma
Romania Investigational Site Number 6420004 Bacau
Romania Investigational Site Number 6420006 Brasov
Romania Investigational Site Number 6420001 Bucuresti
Romania Investigational Site Number 6420008 Buzau
Romania Investigational Site Number 6420003 Cluj Napoca
Romania Investigational Site Number 6420002 Oradea
Romania Investigational Site Number 6420009 Targoviste
Romania Investigational Site Number 6420007 Târgu-Mures
Romania Investigational Site Number 6420005 Timisoara
Slovakia Investigational Site Number 7030006 Bratislava
Slovakia Investigational Site Number 7030009 Lubochna
Slovakia Investigational Site Number 7030002 Lucenec
Slovakia Investigational Site Number 7030005 Malacky
Slovakia Investigational Site Number 7030007 Presov
Slovakia Investigational Site Number 7030001 Roznava
Slovakia Investigational Site Number 7030008 Sabinov
Slovakia Investigational Site Number 7030004 Trencin
Slovakia Investigational Site Number 7030003 Zilina
Spain Investigational Site Number 7240012 Alzira
Spain Investigational Site Number 7240005 Barcelona
Spain Investigational Site Number 7240002 Ferrol
Spain Investigational Site Number 7240008 Málaga
Spain Investigational Site Number 7240011 Pozuelo De Alarcón
Spain Investigational Site Number 7240003 Quart De Poblet
Spain Investigational Site Number 7240006 Sabadell
Spain Investigational Site Number 7240004 Sevilla
Spain Investigational Site Number 7240007 Sevilla
Spain Investigational Site Number 7240009 sEVILLA
United States Investigational Site Number 8400079 Albany New York
United States Investigational Site Number 8400139 Austin Texas
United States Investigational Site Number 8400049 Avon Indiana
United States Investigational Site Number 8400053 Avon Indiana
United States Investigational Site Number 8400085 Avon Indiana
United States Investigational Site Number 8400120 Avon Indiana
United States Investigational Site Number 8400103 Bakersfield California
United States Investigational Site Number 8400033 Baltimore Maryland
United States Investigational Site Number 8400064 Birmingham Alabama
United States Investigational Site Number 8400090 Columbia South Carolina
United States Investigational Site Number 8400019 Columbus Ohio
United States Investigational Site Number 8400130 Council Bluffs Iowa
United States Investigational Site Number 8400001 Dallas Texas
United States Investigational Site Number 8400056 Dayton Ohio
United States Investigational Site Number 8400036 Denver Colorado
United States Investigational Site Number 8400071 Denver Colorado
United States Investigational Site Number 8400118 Edinburg Texas
United States Investigational Site Number 8400041 Evansville Indiana
United States Investigational Site Number 8400018 Fargo North Dakota
United States Investigational Site Number 8400073 Fountain Hills Arizona
United States Investigational Site Number 8400137 Fresno California
United States Investigational Site Number 8400044 Henderson Nevada
United States Investigational Site Number 8400008 Houston Texas
United States Investigational Site Number 8400063 Houston Texas
United States Investigational Site Number 8400106 Houston Texas
United States Investigational Site Number 8400109 Houston Texas
United States Investigational Site Number 8400043 Huntington Park California
United States Investigational Site Number 8400038 Indianapolis Indiana
United States Investigational Site Number 8400114 Jacksonville Florida
United States Investigational Site Number 8400051 Jefferson City Missouri
United States Investigational Site Number 8400124 Lamont California
United States Investigational Site Number 8400027 Lancaster California
United States Investigational Site Number 8400045 Lawrenceville Georgia
United States Investigational Site Number 8400034 Lexington Kentucky
United States Investigational Site Number 8400091 Lexington Kentucky
United States Investigational Site Number 8400013 Los Angeles California
United States Investigational Site Number 8400098 Los Angeles California
United States Investigational Site Number 8400078 Marrero Louisiana
United States Investigational Site Number 8400125 Mentor Ohio
United States Investigational Site Number 8400032 Metairie Louisiana
United States Investigational Site Number 8400133 Miami Florida
United States Investigational Site Number 8400042 Mission Hills California
United States Investigational Site Number 8400020 Morehead City North Carolina
United States Investigational Site Number 8400088 New Orleans Louisiana
United States Investigational Site Number 8400061 New York New York
United States Investigational Site Number 8400123 North Massapequa New York
United States Investigational Site Number 8400014 North Richland Hills Texas
United States Investigational Site Number 8400006 Northridge California
United States Investigational Site Number 8400099 Oklahoma City Oklahoma
United States Investigational Site Number 8400021 Orange California
United States Investigational Site Number 8400054 Orem Utah
United States Investigational Site Number 8400083 Papillion Nebraska
United States Investigational Site Number 8400047 Phoenix Arizona
United States Investigational Site Number 8400058 Port Charlotte Florida
United States Investigational Site Number 8400126 Rialto California
United States Investigational Site Number 8400025 Salt Lake City Utah
United States Investigational Site Number 8400089 San Antonio Texas
United States Investigational Site Number 8400094 Santa Ana California
United States Investigational Site Number 8400135 Schertz Texas
United States Investigational Site Number 8400129 Scottdale Pennsylvania
United States Investigational Site Number 8400075 Shavano Park Texas
United States Investigational Site Number 8400076 Smithfield Pennsylvania
United States Investigational Site Number 8400096 Snellville Georgia
United States Investigational Site Number 8400023 Springfield Illinois
United States Investigational Site Number 8400095 Staten Island New York
United States Investigational Site Number 8400107 Sugar Land Texas
United States Investigational Site Number 8400084 Tampa Florida
United States Investigational Site Number 8400009 Ventura California
United States Investigational Site Number 8400104 Warwick Rhode Island
United States Investigational Site Number 8400092 Weber City Virginia
United States Investigational Site Number 8400112 West Palm Beach Florida
United States Investigational Site Number 8400067 West Seneca New York
United States Investigational Site Number 8400065 Wilmington North Carolina
United States Investigational Site Number 8400111 Yonkers New York

Sponsors (1)

Lead Sponsor Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  Estonia,  Germany,  Israel,  Italy,  Romania,  Slovakia,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 26: Core Period Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least squares (LS) mean and standard error (SE) were obtained from Mixed-effect model with repeated measures (MMRM) to account for missing data using all available post baseline data during the 26 week treatment period. Baseline, Week 26
Primary Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 52: Single Arm Extension Period Change in HbA1c was calculated by subtracting baseline value from Week 52 value. Baseline, Week 52
Secondary Percentage of Participants Reaching HbA1c <7% or <=6.5% at Week 26: Core Period Participants without any available HbA1c assessment at Week 26 were considered as non-responders. Week 26
Secondary Percentage of Participants Reaching HbA1c <7 % or <=6.5% at Week 52: Single Arm Extension Period Participants without any available HbA1c assessment at Week 52 were considered as non-responders. Week 52
Secondary Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26: Core Period Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period. Baseline, Week 26
Secondary Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52: Single Arm Extension Period Change in FPG was calculated by subtracting baseline value from Week 52 value. Baseline, Week 52
Secondary Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 26: Core Period The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period. Baseline, Week 26
Secondary Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 52: Single Arm Extension Period The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. Baseline, Week 52
Secondary Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 26: Core Period The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last observation carried forward (LOCF). Baseline, Week 26
Secondary Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 52: Single Arm Extension Period The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF. Baseline, Week 52
Secondary Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 26: Core Period 2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF. Baseline, Week 26
Secondary Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 52: Single Arm Extension Period 2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before IMP administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF. Baseline, Week 52
Secondary Percentage of Participants Requiring Rescue Therapy During the 26 Week Treatment Period: Core Period Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c >8%. From Baseline to Week 26
Secondary Percentage of Participants Requiring Rescue Therapy During the 52 Week Treatment Period: Single Arm Extension Period Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c >8%. From Week 26 to Week 52
Secondary Change From Baseline in Body Weight at Week 26: Core Period Change in body weight was calculated by subtracting baseline value from Week 26 value. Baseline, Week 26
Secondary Change From Baseline in Body Weight to Week 52: Single Arm Extension Period Change in body weight was calculated by subtracting baseline value from Week 52 value. Baseline, Week 52
Secondary Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Core Period Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of <3.0 mmol/L (54 mg/dL) were also analyzed. From Baseline to Week 26
Secondary Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Single Arm Extension Period Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of <3.0 mmol/L (54 mg/dL) were also analyzed. From Baseline to Week 52
See also
  Status Clinical Trial Phase
Completed NCT02771093 - An Exploratory Study of the Effects of Trelagliptin and Alogliptin on Glucose Variability in Patients With Type 2 Diabetes Mellitus Phase 4
Completed NCT02545842 - Assessment Study of Three Different Fasting Plasma Glucose Targets in Chinese Patients With Type 2 Diabetes Mellitus (BEYOND III/FPG GOAL) Phase 4
Recruiting NCT03436212 - Real-Life Home Glucose Monitoring Over 14 Days in T2D Patients With Intensified Therapy Using Insulin Pump. N/A
Completed NCT03244800 - A Study to Investigate Different Doses of 0382 in Overweight and Obese Subjects With Type 2 Diabetes Mellitus. Phase 2
Completed NCT03960424 - Diabetes Management Program for Hispanic/Latino N/A
Withdrawn NCT02769091 - A Study in Adult Patients With Nonalcoholic Steatohepatitis Who Also Have Type 2 Diabetes Phase 2
Recruiting NCT06065540 - A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor Phase 3
Recruiting NCT05008276 - Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress (PANTHER Study)
Completed NCT04091373 - A Study Investigating the Pharmacokinetics of a Single Dose Administration of Cotadutide Phase 1
Completed NCT03296800 - Study to Evaluate Effects of Probenecid, Rifampin and Verapamil on Bexagliflozin in Healthy Subjects Phase 1
Recruiting NCT06212778 - Relationship Between Nutritional Status, Hand Grip Strength, and Fatigue in Hospitalized Older Adults With Type 2 Diabetes Mellitus.
Completed NCT05979519 - Fresh Carts for Mom's to Improve Food Security and Glucose Management N/A
Recruiting NCT05579314 - XW014 in Healthy Subjects and Patients With Type 2 Diabetes Mellitus (T2DM) Phase 1
Completed NCT03859934 - Metabolic Effects of Melatonin Treatment Phase 1
Terminated NCT03684642 - Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Phase 3
Completed NCT03248401 - Effect of Cilostazol on Carotid Atherosclerosis Estimated by 3D Ultrasound in Patients With Type 2 Diabetes Phase 4
Completed NCT03644134 - A Personalized Intervention to Manage Physiological Stress and Improve Sleep Patterns N/A
Completed NCT05295160 - Fasting-Associated Immune-metabolic Remission of Diabetes N/A
Completed NCT02836873 - Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment Phase 3
Completed NCT02226003 - Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017) Phase 3