Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes on Basal Insulin With Oral Antidiabetic Therapy (EDITION II)

6-Month, Multicenter, Randomized, Open-label, Parallel-group Study Comparing the Efficacy and Safety of a New Formulation of Insulin Glargine and Lantus® Both in Combination With Oral Antihyperglycemic Drug(s) in Patients With Type 2 Diabetes Mellitus With a 6-month Safety Extension Period

Primary Objective:

• To compare the efficacy of insulin glargine new formulation and Lantus in terms of change in Glycated Hemoglobin A1c (HbA1c) from baseline to endpoint (scheduled Month 6) in adult participants with type 2 diabetes mellitus

Secondary Objective:

• To compare the efficacy of insulin glargine new formulation and Lantus in terms of occurrence of nocturnal hypoglycemia

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: HOE901-U300 (new formulation of insulin glargine); Drug: Lantus (Insulin glargine)

Detailed Description

The maximum study duration was up to approximately 58 weeks per participants, consisting of:

• up to 2 week screening period
• 6-month comparative efficacy and safety treatment period
• 6-month comparative safety extension period
• 4-week safety follow-up period in a subset of participants
• a 3-month administration substudy period starting after completion of the 6-month study period for participants willing to in a subset of participants randomized to HOE901-U300

• Study Type: Interventional
• Enrollment (Actual): 811
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Beamsville, Canada, L0R 1B0
    • Investigational Site Number 124024
  • Burlington, Canada, L7M 4Y1
    • Investigational Site Number 124025
  • Calgary, Canada, T2N 4L7
    • Investigational Site Number 124020
  • Chilliwack, Canada, V2P 4M9
    • Investigational Site Number 124019
  • Coquitlam, Canada, V3K 3P4
    • Investigational Site Number 124018
  • Edmonton, Canada, T5C 0A3
    • Investigational Site Number 124016
  • Hamilton, Canada, L8N 3Z5
    • Investigational Site Number 124014
  • Mirabel, Canada, J7J 2K8
    • Investigational Site Number 124004
  • Mississauga, Canada, L5M 2V8
    • Investigational Site Number 124026
  • Red Deer, Canada, T4N 6V7
    • Investigational Site Number 124002
  • Sherbrooke, Canada, J1H 5N4
    • Investigational Site Number 124013
  • Toronto, Canada, M5C 2T2
    • Investigational Site Number 124011
  • Victoria, Canada, V8V 4A1
    • Investigational Site Number 124010
  • Winnipeg, Canada, R3E 3P4
    • Investigational Site Number 124022
• Chile
  • Osorno, Chile, 5311092
    • Investigational Site Number 152014
  • Rancagua, Chile, 2841959
    • Investigational Site Number 152012
  • Santiago, Chile
    • Investigational Site Number 152010
  • Santiago, Chile, 7500710
    • Investigational Site Number 152004
  • Santiago, Chile, 7500010
    • Investigational Site Number 152005
  • Santiago, Chile, 751-0009
    • Investigational Site Number 152003
  • Santiago, Chile, 7980378
    • Investigational Site Number 152001
  • Santiago, Chile, 7980378
    • Investigational Site Number 152013
  • Santiago, Chile, 80004005
    • Investigational Site Number 152002
  • Santiago, Chile, 8053095
    • Investigational Site Number 152007
  • Temuco, Chile, 4813299
    • Investigational Site Number 152006
  • Valdivia, Chile, 56 63
    • Investigational Site Number 152009
• Finland
  • Helsinki, Finland, 00290
    • Investigational Site Number 246001
• France
  • La Rochelle Cedex, France, 17019
    • Investigational Site Number 250001
  • Le Creusot, France, 71200
    • Investigational Site Number 250004
  • Mantes La Jolie, France, 78200
    • Investigational Site Number 250005
  • Nantes, France, 44093
    • Investigational Site Number 250002
  • Strasbourg, France, 67000
    • Investigational Site Number 250009
  • Venissieux, France, 69200
    • Investigational Site Number 250003
• Germany
  • Künzing, Germany, 94550
    • Investigational Site Number 276004
  • Neumünster, Germany, 24534
    • Investigational Site Number 276003
  • Oberhausen, Germany, 46045
    • Investigational Site Number 276008
  • Pirna, Germany, 01796
    • Investigational Site Number 276009
  • Rehlingen-Siersburg, Germany, 66780
    • Investigational Site Number 276007
  • Wangen, Germany, 88239
    • Investigational Site Number 276005
• Hungary
  • Baja, Hungary, 6500
    • Investigational Site Number 348006
  • Budapest, Hungary, 1032
    • Investigational Site Number 348005
  • Budapest, Hungary, 1139
    • Investigational Site Number 348003
  • Budapest, Hungary, 1145
    • Investigational Site Number 348010
  • Budapest, Hungary, 1204
    • Investigational Site Number 348009
  • Eger, Hungary, 3300
    • Investigational Site Number 348002
  • Makó, Hungary, 6900
    • Investigational Site Number 348001
  • Mosonmagyaróvár, Hungary, 9200
    • Investigational Site Number 348008
  • Pápa, Hungary, 8500
    • Investigational Site Number 348004
  • Sátorlaljaújhely, Hungary, 3980
    • Investigational Site Number 348007
• Mexico
  • Acapulco, Mexico, 39670
    • Investigational Site Number 484009
  • Guadalajara, Mexico, 44210
    • Investigational Site Number 484007
  • Guadalajara, Mexico, 44656
    • Investigational Site Number 484008
  • Guadalajara, Mexico, Guadalajara
    • Investigational Site Number 484010
  • Mexico City, Mexico, 11550
    • Investigational Site Number 484006
  • Monterrey, Mexico, 64020
    • Investigational Site Number 484001
  • Monterrey, Mexico, 64240
    • Investigational Site Number 484003
  • Pachuca, Mexico, 42060
    • Investigational Site Number 484004
• Portugal
  • Matosinhos, Portugal
    • Investigational Site Number 620007
  • Porto, Portugal, 4200
    • Investigational Site Number 620004
• Romania
  • Bacau, Romania, 600164
    • Investigational Site Number 642008
  • Brasov, Romania, 500365
    • Investigational Site Number 642009
  • Bucuresti, Romania, 020475
    • Investigational Site Number 642003
  • Bucuresti, Romania, 20475
    • Investigational Site Number 642001
  • Bucuresti, Romania, 20475
    • Investigational Site Number 642002
  • Cluj Napoca, Romania, 400006
    • Investigational Site Number 642014
  • Deva, Romania, 330084
    • Investigational Site Number 642006
  • Hunedoara, Romania, 331057
    • Investigational Site Number 642011
  • Iasi, Romania, 700547
    • Investigational Site Number 642015
  • Oradea, Romania, 410169
    • Investigational Site Number 642013
  • Ploiesti, Romania, 100097
    • Investigational Site Number 642010
  • Resita, Romania, 320076
    • Investigational Site Number 642004
  • Targu Mures, Romania, 540142
    • Investigational Site Number 642007
  • Timisoara, Romania, 300133
    • Investigational Site Number 642012
  • Timisoara, Romania, 300456
    • Investigational Site Number 642005
• Russian Federation
  • Moscow, Russian Federation, 123423
    • Investigational Site Number 643010
  • Moscow, Russian Federation, 129110
    • Investigational Site Number 643007
  • Samara, Russian Federation, 443095
    • Investigational Site Number 643011
  • Saratov, Russian Federation, 410030
    • Investigational Site Number 643002
  • St-Petersburg, Russian Federation, 195257
    • Investigational Site Number 643004
  • St-Petersburg, Russian Federation, 194291
    • Investigational Site Number 643009
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643006
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643014
  • St-Petersburg, Russian Federation, 195112
    • Investigational Site Number 643013
  • St-Petersburg, Russian Federation, 198013
    • Investigational Site Number 643001
  • St. Petersburg, Russian Federation, 194358
    • Investigational Site Number 643008
  • Ufa, Russian Federation, 450000
    • Investigational Site Number 643016
  • Voronezh, Russian Federation, 394018
    • Investigational Site Number 643005
• South Africa
  • Benoni, South Africa, 1501
    • Investigational Site Number 710007
  • Bloemfontein, South Africa, 9301
    • Investigational Site Number 710006
  • Bloemfontein, South Africa, 9301
    • Investigational Site Number 710014
  • Boksburg, South Africa, 1459
    • Investigational Site Number 710002
  • Cape Town, South Africa, 7130
    • Investigational Site Number 710003
  • Cape Town, South Africa, 7500
    • Investigational Site Number 710010
  • Johannesburg, South Africa, 2013
    • Investigational Site Number 710001
  • Pretoria, South Africa, 0001
    • Investigational Site Number 710005
  • Somerset West, South Africa, 7130
    • Investigational Site Number 710012
  • Umkomaas, South Africa, 4170
    • Investigational Site Number 710008
• Spain
  • Barcelona, Spain, 08022
    • Investigational Site Number 724005
  • Malaga, Spain, 29010
    • Investigational Site Number 724003
  • Palma De Mallorca, Spain, 07198
    • Investigational Site Number 724006
  • Sabadell, Spain, 08208
    • Investigational Site Number 724001
  • Sevilla, Spain, 41010
    • Investigational Site Number 724002
  • Valancia, Spain, 46014
    • Investigational Site Number 724004
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Investigational Site Number 840517
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Investigational Site Number 840149
    • Glendale, Arizona, United States, 85306
      • Investigational Site Number 840093
    • Phoenix, Arizona, United States, 85028
      • Investigational Site Number 840069
    • Sun City, Arizona, United States, 85351
      • Investigational Site Number 840110
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840068
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Investigational Site Number 840015
    • Little Rock, Arkansas, United States, 72205
      • Investigational Site Number 840014
    • Little Rock, Arkansas, United States, 72205
      • Investigational Site Number 840114
    • Mountain Home, Arkansas, United States, 72653
      • Investigational Site Number 840018
    • Searcy, Arkansas, United States, 72143
      • Investigational Site Number 840027
  • California
    • Anaheim, California, United States, 92801
      • Investigational Site Number 840074
    • Bell Gardens, California, United States, 90201
      • Investigational Site Number 840509
    • Greenbrae, California, United States, 94904
      • Investigational Site Number 840060
    • La Jolla, California, United States, 92037
      • Investigational Site Number 840057
    • La Mesa, California, United States, 91942
      • Investigational Site Number 840003
    • Los Angeles, California, United States, 90073
      • Investigational Site Number 840026
    • Mission Hills, California, United States, 91345
      • Investigational Site Number 840090
    • Palm Springs, California, United States, 92262
      • Investigational Site Number 840099
    • San Diego, California, United States, 92161
      • Investigational Site Number 840004
    • Santa Barbara, California, United States, 93110
      • Investigational Site Number 840124
    • Tustin, California, United States, 92780
      • Investigational Site Number 840012
  • Colorado
    • Colorado Springs, Colorado, United States, 80906
      • Investigational Site Number 840104
    • Colorado Springs, Colorado, United States, 80909
      • Investigational Site Number 840128
    • Denver, Colorado, United States, 80206
      • Investigational Site Number 840098
  • Florida
    • Brandon, Florida, United States, 33511
      • Investigational Site Number 840518
    • Daytona Beach, Florida, United States, 32117
      • Investigational Site Number 840049
    • Jacksonville, Florida, United States, 32258
      • Investigational Site Number 840008
    • Miami, Florida, United States, 33015
      • Investigational Site Number 840520
    • New Port Richey, Florida, United States, 34652
      • Investigational Site Number 840025
    • Ocoee, Florida, United States, 34761
      • Investigational Site Number 840011
    • Palm Harbor, Florida, United States, 34684
      • Investigational Site Number 840141
    • Pembroke Pines, Florida, United States, 33029
      • Investigational Site Number 840513
  • Georgia
    • Columbus, Georgia, United States, 31901
      • Investigational Site Number 840528
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Investigational Site Number 840050
    • Nampa, Idaho, United States, 83686
      • Investigational Site Number 840107
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Investigational Site Number 840199
    • McHenry, Illinois, United States, 60050
      • Investigational Site Number 840021
    • Springfield, Illinois, United States, 62704
      • Investigational Site Number 840020
  • Indiana
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840089
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840045
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840077
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840088
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840091
    • Evansville, Indiana, United States, 47714
      • Investigational Site Number 840130
    • Lafayette, Indiana, United States, 47904
      • Investigational Site Number 840142
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Investigational Site Number 840041
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Investigational Site Number 840034
    • Baltimore, Maryland, United States, 21237
      • Investigational Site Number 840150
    • Rockville, Maryland, United States, 20852
      • Investigational Site Number 840031
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Investigational Site Number 840063
    • Dearborn, Michigan, United States, 48124
      • Investigational Site Number 840064
    • Flint, Michigan, United States, 48504
      • Investigational Site Number 840094
    • Southfield, Michigan, United States, 48034
      • Investigational Site Number 840023
  • Minnesota
    • Eagan, Minnesota, United States, 55122
      • Investigational Site Number 840066
    • Minneapolis, Minnesota, United States, 55416
      • Investigational Site Number 840081
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • Investigational Site Number 840158
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Investigational Site Number 840526
  • Montana
    • Butte, Montana, United States, 59701
      • Investigational Site Number 840502
  • Nebraska
    • Fremont, Nebraska, United States, 68025
      • Investigational Site Number 840084
    • Omaha, Nebraska, United States, 68130
      • Investigational Site Number 840085
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Investigational Site Number 840162
    • Las Vegas, Nevada, United States, 89117
      • Investigational Site Number 840527
    • Las Vegas, Nevada, United States, 89148
      • Investigational Site Number 840056
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Investigational Site Number 840135
    • Toms River, New Jersey, United States, 08721
      • Investigational Site Number 840145
    • Toms River, New Jersey, United States, 08753
      • Investigational Site Number 840087
  • North Carolina
    • Calabash, North Carolina, United States, 28467
      • Investigational Site Number 840140
    • Hickory, North Carolina, United States, 28601
      • Investigational Site Number 840139
    • Hickory, North Carolina, United States, 28601
      • Investigational Site Number 840153
    • Wilmington, North Carolina, United States, 28401
      • Investigational Site Number 840047
    • Winston-Salem, North Carolina, United States, 27103
      • Investigational Site Number 840024
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Investigational Site Number 840065
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Investigational Site Number 840007
    • Columbus, Ohio, United States, 43213
      • Investigational Site Number 840097
    • Dayton, Ohio, United States, 45439
      • Investigational Site Number 840113
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 840108
  • Oregon
    • Eugene, Oregon, United States
      • Investigational Site Number 840504
    • Medford, Oregon, United States, 97504
      • Investigational Site Number 840080
  • Pennsylvania
    • Tipton, Pennsylvania, United States, 16684
      • Investigational Site Number 840148
    • Uniontown, Pennsylvania, United States, 15401
      • Investigational Site Number 840005
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Investigational Site Number 840076
    • Simpsonville, South Carolina, United States, 29681
      • Investigational Site Number 840503
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Investigational Site Number 840048
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Investigational Site Number 840028
    • Chattanooga, Tennessee, United States, 37404
      • Investigational Site Number 840038
    • Knoxville, Tennessee, United States, 37912
      • Investigational Site Number 840042
    • Memphis, Tennessee, United States, 38119
      • Investigational Site Number 840160
    • Memphis, Tennessee, United States, 38125
      • Investigational Site Number 840033
  • Texas
    • Austin, Texas, United States, 78731
      • Investigational Site Number 840022
    • Austin, Texas, United States, 78758
      • Investigational Site Number 840078
    • Corpus Christi, Texas, United States, 78404
      • Investigational Site Number 840519
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 840001
    • Dallas, Texas, United States, 75231
      • Investigational Site Number 840159
    • Dallas, Texas, United States, 75246
      • Investigational Site Number 840115
    • Houston, Texas, United States, 77030
      • Investigational Site Number 840079
    • Houston, Texas, United States, 77074
      • Investigational Site Number 840514
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 840525
    • San Antonio, Texas, United States, 78258
      • Investigational Site Number 840161
  • Utah
    • Draper, Utah, United States, 84020
      • Investigational Site Number 840009
    • Orem, Utah, United States, 84058
      • Investigational Site Number 840037
    • Salt Lake City, Utah, United States, 84107
      • Investigational Site Number 840510
  • Virginia
    • Chesapeake, Virginia, United States, 23321
      • Investigational Site Number 840032
    • Norfolk, Virginia, United States, 23510
      • Investigational Site Number 840040
    • Richmond, Virginia, United States, 23235
      • Investigational Site Number 840095
    • Williamsburg, Virginia, United States, 23185
      • Investigational Site Number 840072
    • Winchester, Virginia, United States, 22601
      • Investigational Site Number 840134
  • Washington
    • Olympia, Washington, United States, 98502
      • Investigational Site Number 840523
    • Walla Walla, Washington, United States, 99362
      • Investigational Site Number 840122
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209-0996
      • Investigational Site Number 840019

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

• Substudy inclusion criteria:

  • Completion of the 6-month study period in main study (Visit 10)
  • Randomized and treated with insulin glargine new formulation during the 6- month treatment period (Baseline - Month 6)

Exclusion criteria:

• Age less than (<) 18 years
• HbA1c <7.0% or greater than (>) 10% at screening
• Diabetes other than type 2 diabetes mellitus
• Less than 6 months on basal insulin treatment together with oral antihyperglycemic drug(s) and self-monitoring of blood glucose
• Participants using sulfonylurea in the last 2 months before screening visit
• Any contraindication to use of insulin glargine as defined in the national product label
• Use of insulin pump in the last 6 months before screening
• Initiation of new glucose-lowering medications in the last 3 months before screening visit
• History or presence of significant diabetic retinopathy or macular edema likely to require laser or injectable drugs or surgical treatment during the study period
• Pregnant or breast-feeding women or women who intend to become pregnant during the study period

• Substudy exclusion criteria:

  • Participant not willing to use the adaptable injection intervals on at least two days per week

The above information is 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: HOE901-U300	Drug: HOE901-U300 (new formulation of insulin glargine); HOE901-U300 (new insulin glargine 300 units per milliliter [U/mL]) subcutaneous (SC) injection once daily (evening) for 12 months in combination with oral antidiabetic drug(s). Dose titration seeking fasting plasma glucose 4.4 - 5.6 millimole per liter (mmol/L) (80 - 100 milligram per deciliter [mg/dL]). After 6 months participants were proposed to participate to the administration substudy and to receive either HOE901-U300 once daily at intervals of 24 +/- 3 hours (adaptable dosing intervals) or to continue once daily injections of HOE901-U300 every 24 hours (fixed dosing intervals) up to Month 9.
Active Comparator: Lantus	Drug: Lantus (Insulin glargine); Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months in combination with oral antidiabetic drug(s). Dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L (80 - 100 mg/dL).; Other Names: Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c From Baseline to Month 6 Endpoint	Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint	Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time), regardless the participant was awake or woke up because of the event. Severe hypoglycemia was an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Confirmed hypoglycemia was an event associated with plasma glucose less than or equal to (<=) 3.9 mmol/L (70 milligram per deciliter [mg/dL]). Only measurements performed before initiation of rescue therapy were considered in the analysis.	Week 9 Up to Month 6
Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint	Preinjection SMPG was measured within 30 minutes prior to the injection of the study drug. Average was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint	Preinjection SMPG was measured within 30 minutes prior to the injection of the study drug. Variability was assessed by the mean of co-efficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 3 SMPG measured during the 7 days preceding the assessment visit. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Percentage of Participants With HbA1c <7% at Month 6 Endpoint	Only measurements performed before initiation of rescue therapy were considered in the analysis.	Month 6
Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint	Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint	Only measurements performed before initiation of rescue therapy were considered in the analysis.	Month 6
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint	Change in each time-point of 8-point SMPG profile: 03:00 hours (clock time) at night; before and 2 hours after breakfast; before and 2 hours after lunch; before and 2 hours after dinner; and at bedtime. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint	Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint	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 and 4-8 scores and ranges between 0 and 36, where higher scores indicate more treatment satisfaction. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12	Hypoglycemia events were Severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); Documented symptomatic hypoglycemia (typical symptoms of hypoglycemia with plasma glucose level of <=3.9 mmol/L [70 mg/dL]); Asymptomatic hypoglycemia (no typical symptoms of hypoglycemia but plasma glucose level <=3.9 mmol/L); Probable symptomatic hypoglycemia (an event during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination, but was presumably caused by a plasma glucose level <=3.9 mmol/L, symptoms treated with oral carbohydrate without a test of plasma glucose); Relative hypoglycemia (an event during which the person with diabetes reported any of the typical symptoms of hypoglycemia, and interpreted the symptoms as indicative of hypoglycemia, but plasma glucose level >3.9 mmol/L); Severe and/or confirmed a hypoglycemia (plasma glucose <=3.9 mmol/L).	Up to Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c From Month 6 to Month 9	Substudy comparing fixed dosing regimen (every 24 hours) vs. adaptive dosing regimen (every 24 +/- 3 hours) in a subset of participants randomized to HOE901-U300 and treated for 6 months. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Month 6 up to Month 9

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Yale JF, Aroda VR, Charbonnel B, Sinclair AJ, Trescoli C, Cahn A, Bigot G, Merino-Trigo A, Brulle-Wohlhueter C, Bolli GB, Ritzel R. Glycaemic control and hypoglycaemia risk with insulin glargine 300 U/mL versus glargine 100 U/mL: A patient-level meta-analysis examining older and younger adults with type 2 diabetes. Diabetes Metab. 2020 Apr;46(2):110-118. doi: 10.1016/j.diabet.2018.10.002. Epub 2018 Oct 23.
• Bolli GB, Wysham C, Fisher M, Chevalier S, Cali AMG, Leroy B, Riddle MC. A post-hoc pooled analysis to evaluate the risk of hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus 100 U/mL (Gla-100) over wider nocturnal windows in individuals with type 2 diabetes on a basal-only insulin regimen. Diabetes Obes Metab. 2019 Feb;21(2):402-407. doi: 10.1111/dom.13515. Epub 2018 Oct 2.
• Yale JF, Pettus JH, Brito-Sanfiel M, Lavalle-Gonzalez F, Merino-Trigo A, Stella P, Chevalier S, Buzzetti R. The effect of concomitant DPPIVi use on glycaemic control and hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes: A patient-level meta-analysis of EDITION 2 and 3. PLoS One. 2018 Jan 25;13(1):e0190579. doi: 10.1371/journal.pone.0190579. eCollection 2018.
• Bonadonna RC, Renard E, Cheng A, Fritsche A, Cali A, Melas-Melt L, Umpierrez GE. Switching to insulin glargine 300 U/mL: Is duration of prior basal insulin therapy important? Diabetes Res Clin Pract. 2018 Aug;142:19-25. doi: 10.1016/j.diabres.2018.03.041. Epub 2018 Apr 9.
• Yki-Jarvinen H, Bergenstal R, Ziemen M, Wardecki M, Muehlen-Bartmer I, Boelle E, Riddle MC; EDITION 2 Study Investigators. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care. 2014 Dec;37(12):3235-43. doi: 10.2337/dc14-0990. Epub 2014 Sep 5.
• Yki-Jarvinen H, Bergenstal RM, Bolli GB, Ziemen M, Wardecki M, Muehlen-Bartmer I, Maroccia M, Riddle MC. Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension. Diabetes Obes Metab. 2015 Dec;17(12):1142-9. doi: 10.1111/dom.12532. Epub 2015 Sep 14.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: December 16, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 26, 2011

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

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; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: EFC11629; 2010-023770-39 (EudraCT Number); U1111-1118-6943 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org