Efficacy and Safety of Toujeo® Versus Tresiba® in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist
- Conditions
- Diabetes Mellitus, Type 2
- Interventions
- Drug: Insulin glargine, 300U/mLDrug: Insulin degludec, 100 U/mLDrug: Non-insulin anti-diabetic treatment
- Registration Number
- NCT02738151
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To demonstrate the noninferiority in the efficacy of Toujeo® to Tresiba® in glycated hemoglobin (HbA1c) change from Baseline to Week 24.
Secondary Objectives:
Change From Baseline in HbA1c to Week 12
To assess the effects of the insulin Toujeo® in comparison with insulin Tresiba® at week 12 and week 24 on:
* Change in Fasting plasma glucose (FPG);
* Change in Fasting self-monitored plasma glucose (SMPG) and 4-point SMPG and 8-point SMPG profile;
* Percentage of participants reaching HbA1c targets \<7% or ≤6.5%;
* Percentage of participants reaching HbA1c targets \<7% or ≤6.5% without severe and/or confirmed hypoglycemia
* Frequency of occurrence and diurnal distribution of hypoglycemia by American Diabetes Association (ADA) category of hypoglycemia.
To assess the safety in each treatment group.
To assess the treatment effects in each treatment group on Patient Reported Outcomes (PRO).
Percentage of participants requiring rescue therapy.
- Detailed Description
The maximum study duration per participant was approximately 27 weeks: an up to 2-week screening period, a 24-week randomized treatment period (including 12 weeks active titration), and a 7-day posttreatment safety follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 929
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Toujeo Insulin glargine, 300U/mL Toujeo® (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 24 on top of non-insulin antidiabetic treatment. Tresiba Insulin degludec, 100 U/mL Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment . Tresiba Non-insulin anti-diabetic treatment Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment . Toujeo Non-insulin anti-diabetic treatment Toujeo® (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
- Primary Outcome Measures
Name Time Method Change From Baseline in HbA1c to Week 24 Baseline, Week 24 Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Adjusted Least Square (LS) means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 24-week on-treatment period.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 Baseline, Week 12 and Week 24 Adjusted LS means were obtained from MMRM.
Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 Week 12, and Week 24 Only the post-baseline HbA1c measurements before rescue and during the 12 week and 24-week on-treatment period were considered in the analysis.
Change From Baseline in HbA1c to Week 12 Baseline, Week 12 Change in HbA1c was calculated by subtracting baseline value from Week 12 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.
Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 Baseline, Week 12 and Week 24 The 8-point SMPG profile was measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Adjusted LS means were obtained from MMRM.
Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event Week 12, and Week 24 Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed by plasma glucose =\<3.9 mmol/L (=\<70 mg/dL).
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Day 1-Week 12, Week 13-Week 24, and 24 Week Period Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =\<70 mg/dL (=\<3.9 mmol/L), or \< 54 mg/dL (\<3.0 mmol/L).
Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 Baseline, Week 12 and Week 24 Adjusted LS means were obtained from MMRM. Variability was assessed by the mean of coefficient of variation calculated over at least 3 SMPG measured during the 7 days preceding the given visit.
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 Baseline, Week 12 and Week 24 Change in FPG was calculated by subtracting baseline value from Week 12 and Week 24 value. Adjusted LS means were obtained from MMRM including post baseline values during the 24-week on-treatment period.
Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24 Baseline, Week 12 and Week 24 Only the insulin dose measurements performed before initiation of rescue therapy and during the on-treatment period were considered in the analysis.
Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period Baseline 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. Threshold values at Week 12: FPG \>200 mg/dL (11 mmol/L), or HbA1c \>8.5%.
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Day 1-Week 12, Week 13-Week 24, and 24 Week Period Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =\<70 mg/dL (=\<3.9 mmol/L), or \< 54 mg/dL (\<3.0 mmol/L). Assessment was done by treatment period (for =\<12 weeks, for \>12 weeks to =\<24 weeks (24W)). Percentage of participants with at least one hypoglycemia (hypo) event at any time of the day were reported.
Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 Baseline, Week 12 and Week 24 Fasting SMPG was measured by the participant before breakfast and before the administration of the glucose-lowering agents once a day during the study. Adjusted LS means were obtained from MMRM including post baseline values during the 24 week on treatment period.
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Baseline, Week 12 and Week 24 8-point SMPG profiles were measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Baseline, Week 12 and Week 24 4-point SMPG profiles were measured at the following 4 points: prebreakfast, prelunch, predinner and bedtime.
Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period Baseline to Week 24 Percentage of participants With Sulphonylurea or Meglitinide dose reduction/ discontinuation due to Hypoglycemia during 24 Week treatment period were reported. Only participants with Sulphonylurea or meglitinides at Screening as per actual strata were taken into account in this analysis.
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Day 1-Week 12, Week 13-Week 24, and 24 Week Period Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycaemia event was a severe event or an event confirmed with plasma glucose =\<70 mg/dL (=\<3.9 mmol/L), or \< 54 mg/dL (\<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time). Assessment was done by treatment period (for =\<12 weeks, for \>12 weeks to =\<24 weeks).
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Day 1-Week 12, Week 13-Week 24, and 24 Week Period Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =\<70 mg/dL (=\<3.9 mmol/L), or \< 54 mg/dL (\<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time).
Trial Locations
- Locations (158)
Investigational Site Number 840075
🇺🇸Bradenton, Florida, United States
Investigational Site Number 840007
🇺🇸Dallas, Texas, United States
Investigational Site Number 840036
🇺🇸Arlington Heights, Illinois, United States
Investigational Site Number 840086
🇺🇸Dallas, Texas, United States
Investigational Site Number 840091
🇺🇸Los Angeles, California, United States
Investigational Site Number 840027
🇺🇸Houston, Texas, United States
Investigational Site Number 840004
🇺🇸Houston, Texas, United States
Investigational Site Number 348003
🇭🇺Gyöngyös, Hungary
Investigational Site Number 840065
🇺🇸Van Nuys, California, United States
Investigational Site Number 840018
🇺🇸Port Charlotte, Florida, United States
Investigational Site Number 840061
🇺🇸Paris, Kentucky, United States
Investigational Site Number 840048
🇺🇸Chesterfield, Missouri, United States
Investigational Site Number 840023
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 840094
🇺🇸San Antonio, Texas, United States
Investigational Site Number 840032
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 840066
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840022
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 380010
🇮🇹Chieti, Italy
Investigational Site Number 840084
🇺🇸Olive Branch, Mississippi, United States
Investigational Site Number 840006
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 840097
🇺🇸Greenville, South Carolina, United States
Investigational Site Number 840079
🇺🇸Bristol, Tennessee, United States
Investigational Site Number 100001
🇧🇬Sofia, Bulgaria
Investigational Site Number 300005
🇬🇷Alexandroupolis, Greece
Investigational Site Number 376001
🇮🇱Haifa, Israel
Investigational Site Number 376006
🇮🇱Tel Aviv, Israel
Investigational Site Number 642003
🇷🇴Cluj-Napoca, Romania
Investigational Site Number 300001
🇬🇷Athens, Greece
Investigational Site Number 300002
🇬🇷Athens, Greece
Investigational Site Number 376009
🇮🇱Kfar Saba, Israel
Investigational Site Number 642007
🇷🇴Brasov, Romania
Investigational Site Number 642004
🇷🇴Targu-Mures, Romania
Investigational Site Number 756001
🇨🇭St. Gallen, Switzerland
Investigational Site Number 840093
🇺🇸Anderson, South Carolina, United States
Investigational Site Number 840069
🇺🇸Simpsonville, South Carolina, United States
Investigational Site Number 840077
🇺🇸New Tazewell, Tennessee, United States
Investigational Site Number 348001
🇭🇺Budapest, Hungary
Investigational Site Number 100002
🇧🇬Sofia, Bulgaria
Investigational Site Number 642008
🇷🇴Brasov, Romania
Investigational Site Number 642015
🇷🇴Bucuresti, Romania
Investigational Site Number 642012
🇷🇴Oradea, Romania
Investigational Site Number 642010
🇷🇴Targu-Mures, Romania
Investigational Site Number 688002
🇷🇸Nis, Serbia
Investigational Site Number 703002
🇸🇰Lubochna, Slovakia
Investigational Site Number 756003
🇨🇭Olten, Switzerland
Investigational Site Number 840057
🇺🇸Flint, Michigan, United States
Investigational Site Number 840044
🇺🇸North Myrtle Beach, South Carolina, United States
Investigational Site Number 840088
🇺🇸Knoxville, Tennessee, United States
Investigational Site Number 840045
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 840031
🇺🇸Linden, New Jersey, United States
Investigational Site Number 300003
🇬🇷Athens, Greece
Investigational Site Number 376004
🇮🇱Haifa, Israel
Investigational Site Number 376008
🇮🇱Haifa, Israel
Investigational Site Number 642014
🇷🇴Iasi, Romania
Investigational Site Number 348004
🇭🇺Budapest, Hungary
Investigational Site Number 348002
🇭🇺Budapest, Hungary
Investigational Site Number 376002
🇮🇱Petach tikva, Israel
Investigational Site Number 376003
🇮🇱Tel Hashomer, Israel
Investigational Site Number 642005
🇷🇴Oradea, Romania
Investigational Site Number 840038
🇺🇸Sheffield, Alabama, United States
Investigational Site Number 840051
🇺🇸Anaheim, California, United States
Investigational Site Number 840002
🇺🇸La Jolla, California, United States
Investigational Site Number 840081
🇺🇸Chino, California, United States
Investigational Site Number 840016
🇺🇸Huntington Park, California, United States
Investigational Site Number 840030
🇺🇸Torrance, California, United States
Investigational Site Number 840058
🇺🇸Northridge, California, United States
Investigational Site Number 840021
🇺🇸Palm Springs, California, United States
Investigational Site Number 840087
🇺🇸Santa Ana, California, United States
Investigational Site Number 840076
🇺🇸New Port Richey, Florida, United States
Investigational Site Number 840026
🇺🇸Ocoee, Florida, United States
Investigational Site Number 840052
🇺🇸Palm Harbor, Florida, United States
Investigational Site Number 840071
🇺🇸Lawrenceville, Georgia, United States
Investigational Site Number 840085
🇺🇸Roswell, Georgia, United States
Investigational Site Number 840072
🇺🇸Statesboro, Georgia, United States
Investigational Site Number 840039
🇺🇸Stockbridge, Georgia, United States
Investigational Site Number 840010
🇺🇸Chicago, Illinois, United States
Investigational Site Number 840063
🇺🇸Council Bluffs, Iowa, United States
Investigational Site Number 840005
🇺🇸Avon, Indiana, United States
Investigational Site Number 840101
🇺🇸Des Moines, Iowa, United States
Investigational Site Number 840011
🇺🇸Hyattsville, Maryland, United States
Investigational Site Number 840098
🇺🇸Des Moines, Iowa, United States
Investigational Site Number 840096
🇺🇸West Des Moines, Iowa, United States
Investigational Site Number 840001
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840033
🇺🇸Troy, Michigan, United States
Investigational Site Number 840041
🇺🇸Flint, Michigan, United States
Investigational Site Number 840060
🇺🇸Hickory, North Carolina, United States
Investigational Site Number 840064
🇺🇸Morganton, North Carolina, United States
Investigational Site Number 840043
🇺🇸Wilmington, North Carolina, United States
Investigational Site Number 840082
🇺🇸Winston-Salem, North Carolina, United States
Investigational Site Number 840070
🇺🇸Greer, South Carolina, United States
Investigational Site Number 840025
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 840029
🇺🇸Beaver, Pennsylvania, United States
Investigational Site Number 840056
🇺🇸Downingtown, Pennsylvania, United States
Investigational Site Number 840046
🇺🇸Houston, Texas, United States
Investigational Site Number 840040
🇺🇸Houston, Texas, United States
Investigational Site Number 840054
🇺🇸Hurst, Texas, United States
Investigational Site Number 840008
🇺🇸Missouri City, Texas, United States
Investigational Site Number 840017
🇺🇸Mesquite, Texas, United States
Investigational Site Number 840009
🇺🇸Sugar Land, Texas, United States
Investigational Site Number 840095
🇺🇸Ogden, Utah, United States
Investigational Site Number 840053
🇺🇸Waco, Texas, United States
Investigational Site Number 840024
🇺🇸Norfolk, Virginia, United States
Investigational Site Number 840020
🇺🇸Richmond, Virginia, United States
Investigational Site Number 840012
🇺🇸Renton, Washington, United States
Investigational Site Number 100003
🇧🇬Sofia, Bulgaria
Investigational Site Number 191001
🇭🇷Rijeka, Croatia
Investigational Site Number 191002
🇭🇷Rijeka, Croatia
Investigational Site Number 191003
🇭🇷Zagreb, Croatia
Investigational Site Number 203009
🇨🇿Hlucin, Czechia
Investigational Site Number 203005
🇨🇿Liberec, Czechia
Investigational Site Number 203006
🇨🇿Jilove u Prahy, Czechia
Investigational Site Number 203001
🇨🇿Pardubice, Czechia
Investigational Site Number 203007
🇨🇿Praha 1, Czechia
Investigational Site Number 203004
🇨🇿Vsetin, Czechia
Investigational Site Number 203002
🇨🇿Praha 8, Czechia
Investigational Site Number 203008
🇨🇿Praha 2, Czechia
Investigational Site Number 208003
🇩🇰Aarhus, Denmark
Investigational Site Number 208002
🇩🇰Hillerød, Denmark
Investigational Site Number 208001
🇩🇰København NV., Denmark
Investigational Site Number 250001
🇫🇷Nantes cedex 01, France
Investigational Site Number 208004
🇩🇰Odense, Denmark
Investigational Site Number 250002
🇫🇷La Roche Sur Yon, France
Investigational Site Number 250003
🇫🇷La Rochelle Cedex 1, France
Investigational Site Number 250005
🇫🇷POITIERS Cedex, France
Investigational Site Number 250006
🇫🇷Nimes, France
Investigational Site Number 250007
🇫🇷Venissieux, France
Investigational Site Number 376007
🇮🇱Tel-Aviv, Israel
Investigational Site Number 380014
🇮🇹Milano, Italy
Investigational Site Number 380002
🇮🇹Moncalieri, Italy
Investigational Site Number 380007
🇮🇹Bari, Italy
Investigational Site Number 380009
🇮🇹Catanzaro, Italy
Investigational Site Number 380011
🇮🇹Napoli, Italy
Investigational Site Number 380015
🇮🇹Roma, Italy
Investigational Site Number 380008
🇮🇹Roma, Italy
Investigational Site Number 380016
🇮🇹Roma, Italy
Investigational Site Number 380013
🇮🇹Sesto San Giovanni, Italy
Investigational Site Number 380005
🇮🇹Torino, Italy
Investigational Site Number 380012
🇮🇹Verona, Italy
Investigational Site Number 642001
🇷🇴Bucharest, Romania
Investigational Site Number 642009
🇷🇴Constanta, Romania
Investigational Site Number 642013
🇷🇴Bucharest, Romania
Investigational Site Number 688001
🇷🇸Belgrade, Serbia
Investigational Site Number 642006
🇷🇴Targu-Mures, Romania
Investigational Site Number 752102
🇸🇪Lund, Sweden
Investigational Site Number 688003
🇷🇸Nis, Serbia
Investigational Site Number 703006
🇸🇰Kosice, Slovakia
Investigational Site Number 703001
🇸🇰Moldava nad Bodvou, Slovakia
Investigational Site Number 703003
🇸🇰Sabinov, Slovakia
Investigational Site Number 703005
🇸🇰Trebisov, Slovakia
Investigational Site Number 752101
🇸🇪Skövde, Sweden
Investigational Site Number 826008
🇬🇧Lincoln, United Kingdom
Investigational Site Number 826001
🇬🇧Chertsey, United Kingdom
Investigational Site Number 826005
🇬🇧Gillingham, United Kingdom
Investigational Site Number 826002
🇬🇧London, United Kingdom
Investigational Site Number 826009
🇬🇧Manchester, United Kingdom
Investigational Site Number 826006
🇬🇧Margate, United Kingdom
Investigational Site Number 826004
🇬🇧Swansea, United Kingdom
Investigational Site Number 840080
🇺🇸Palm Harbor, Florida, United States