Clinical trial NCT01499095: Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes on Basal Insulin With Oral Antidiabetic Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-12-26
Enrollment: 811
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Change in HbA1c From Baseline to Month 6 Endpoint
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint
timeFrame: Week 9 Up to Month 6
measure: Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint
timeFrame: Baseline, Month 6
measure: Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint
timeFrame: Baseline, Month 6
measure: Percentage of Participants With HbA1c <7% at Month 6 Endpoint
timeFrame: Month 6
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint
timeFrame: Baseline, Month 6
measure: Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint
timeFrame: Month 6
measure: Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint
timeFrame: Baseline, Month 6
measure: Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint
timeFrame: Baseline, Month 6
measure: Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint
timeFrame: Baseline, Month 6
measure: Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12
timeFrame: Up to Month 12
Other outcomes:
measure: Change in HbA1c From Month 6 to Month 9
timeFrame: Month 6 up to Month 9
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840517
state: Alabama
city: Chandler
country: United States
facility: Investigational Site Number 840149
state: Arizona
city: Glendale
country: United States
facility: Investigational Site Number 840093
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 840069
state: Arizona
city: Sun City
country: United States
facility: Investigational Site Number 840110
state: Arizona
city: Tempe
country: United States
facility: Investigational Site Number 840068
state: Arizona
city: Hot Springs
country: United States
facility: Investigational Site Number 840015
state: Arkansas
city: Little Rock
country: United States
facility: Investigational Site Number 840014
state: Arkansas
city: Little Rock
country: United States
facility: Investigational Site Number 840114
state: Arkansas
city: Mountain Home
country: United States
facility: Investigational Site Number 840018
state: Arkansas
city: Searcy
country: United States
facility: Investigational Site Number 840027
state: Arkansas
city: Anaheim
country: United States
facility: Investigational Site Number 840074
state: California
city: Bell Gardens
country: United States
facility: Investigational Site Number 840509
state: California
city: Greenbrae
country: United States
facility: Investigational Site Number 840060
state: California
city: La Jolla
country: United States
facility: Investigational Site Number 840057
state: California
city: La Mesa
country: United States
facility: Investigational Site Number 840003
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840026
state: California
city: Mission Hills
country: United States
facility: Investigational Site Number 840090
state: California
city: Palm Springs
country: United States
facility: Investigational Site Number 840099
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840004
state: California
city: Santa Barbara
country: United States
facility: Investigational Site Number 840124
state: California
city: Tustin
country: United States
facility: Investigational Site Number 840012
state: California
city: Colorado Springs
country: United States
facility: Investigational Site Number 840104
state: Colorado
city: Colorado Springs
country: United States
facility: Investigational Site Number 840128
state: Colorado
city: Denver
country: United States
facility: Investigational Site Number 840098
state: Colorado
city: Brandon
country: United States
facility: Investigational Site Number 840518
state: Florida
city: Daytona Beach
country: United States
facility: Investigational Site Number 840049
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840008
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840520
state: Florida
city: New Port Richey
country: United States
facility: Investigational Site Number 840025
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 840011
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 840141
state: Florida
city: Pembroke Pines
country: United States
facility: Investigational Site Number 840513
state: Florida
city: Columbus
country: United States
facility: Investigational Site Number 840528
state: Georgia
city: Idaho Falls
country: United States
facility: Investigational Site Number 840050
state: Idaho
city: Nampa
country: United States
facility: Investigational Site Number 840107
state: Idaho
city: Chicago
country: United States
facility: Investigational Site Number 840199
state: Illinois
city: McHenry
country: United States
facility: Investigational Site Number 840021
state: Illinois
city: Springfield
country: United States
facility: Investigational Site Number 840020
state: Illinois
city: Avon
country: United States
facility: Investigational Site Number 840045
state: Indiana
city: Avon
country: United States
facility: Investigational Site Number 840077
state: Indiana
city: Avon
country: United States
facility: Investigational Site Number 840088
state: Indiana
city: Avon
country: United States
facility: Investigational Site Number 840089
state: Indiana
city: Avon
country: United States
facility: Investigational Site Number 840091
state: Indiana
city: Evansville
country: United States
facility: Investigational Site Number 840130
state: Indiana
city: Lafayette
country: United States
facility: Investigational Site Number 840142
state: Indiana
city: Paducah
country: United States
facility: Investigational Site Number 840041
state: Kentucky
city: Baltimore
country: United States
facility: Investigational Site Number 840034
state: Maryland
city: Baltimore
country: United States
facility: Investigational Site Number 840150
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 840031
state: Maryland
city: Ann Arbor
country: United States
facility: Investigational Site Number 840063
state: Michigan
city: Dearborn
country: United States
facility: Investigational Site Number 840064
state: Michigan
city: Flint
country: United States
facility: Investigational Site Number 840094
state: Michigan
city: Southfield
country: United States
facility: Investigational Site Number 840023
state: Michigan
city: Eagan
country: United States
facility: Investigational Site Number 840066
state: Minnesota
city: Minneapolis
country: United States
facility: Investigational Site Number 840081
state: Minnesota
city: Biloxi
country: United States
facility: Investigational Site Number 840158
state: Mississippi
city: Chesterfield
country: United States
facility: Investigational Site Number 840526
state: Missouri
city: Butte
country: United States
facility: Investigational Site Number 840502
state: Montana
city: Fremont
country: United States
facility: Investigational Site Number 840084
state: Nebraska
city: Omaha
country: United States
facility: Investigational Site Number 840085
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational Site Number 840162
state: Nevada
city: Las Vegas
country: United States
facility: Investigational Site Number 840527
state: Nevada
city: Las Vegas
country: United States
facility: Investigational Site Number 840056
state: Nevada
city: Summit
country: United States
facility: Investigational Site Number 840135
state: New Jersey
city: Toms River
country: United States
facility: Investigational Site Number 840145
state: New Jersey
city: Toms River
country: United States
facility: Investigational Site Number 840087
state: New Jersey
city: Calabash
country: United States
facility: Investigational Site Number 840140
state: North Carolina
city: Hickory
country: United States
facility: Investigational Site Number 840139
state: North Carolina
city: Hickory
country: United States
facility: Investigational Site Number 840153
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 840047
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigational Site Number 840024
state: North Carolina
city: Fargo
country: United States
facility: Investigational Site Number 840065
state: North Dakota
city: Cincinnati
country: United States
facility: Investigational Site Number 840007
state: Ohio
city: Columbus
country: United States
facility: Investigational Site Number 840097
state: Ohio
city: Dayton
country: United States
facility: Investigational Site Number 840113
state: Ohio
city: Maumee
country: United States
facility: Investigational Site Number 840108
state: Ohio
city: Eugene
country: United States
facility: Investigational Site Number 840504
state: Oregon
city: Medford
country: United States
facility: Investigational Site Number 840080
state: Oregon
city: Tipton
country: United States
facility: Investigational Site Number 840148
state: Pennsylvania
city: Uniontown
country: United States
facility: Investigational Site Number 840005
state: Pennsylvania
city: Greer
country: United States
facility: Investigational Site Number 840076
state: South Carolina
city: Simpsonville
country: United States
facility: Investigational Site Number 840503
state: South Carolina
city: Rapid City
country: United States
facility: Investigational Site Number 840048
state: South Dakota
city: Bristol
country: United States
facility: Investigational Site Number 840028
state: Tennessee
city: Chattanooga
country: United States
facility: Investigational Site Number 840038
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 840042
state: Tennessee
city: Memphis
country: United States
facility: Investigational Site Number 840160
state: Tennessee
city: Memphis
country: United States
facility: Investigational Site Number 840033
state: Tennessee
city: Austin
country: United States
facility: Investigational Site Number 840022
state: Texas
city: Austin
country: United States
facility: Investigational Site Number 840078
state: Texas
city: Corpus Christi
country: United States
facility: Investigational Site Number 840519
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840001
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840159
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840115
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840079
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840514
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840525
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840161
state: Texas
city: Draper
country: United States
facility: Investigational Site Number 840009
state: Utah
city: Orem
country: United States
facility: Investigational Site Number 840037
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 840510
state: Utah
city: Chesapeake
country: United States
facility: Investigational Site Number 840032
state: Virginia
city: Norfolk
country: United States
facility: Investigational Site Number 840040
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840095
state: Virginia
city: Williamsburg
country: United States
facility: Investigational Site Number 840072
state: Virginia
city: Winchester
country: United States
facility: Investigational Site Number 840134
state: Virginia
city: Olympia
country: United States
facility: Investigational Site Number 840523
state: Washington
city: Walla Walla
country: United States
facility: Investigational Site Number 840122
state: Washington
city: Milwaukee
country: United States
facility: Investigational Site Number 840019
state: Wisconsin
city: Beamsville
country: Canada
facility: Investigational Site Number 124024
city: Burlington
country: Canada
facility: Investigational Site Number 124025
city: Calgary
country: Canada
facility: Investigational Site Number 124020
city: Chilliwack
country: Canada
facility: Investigational Site Number 124019
city: Coquitlam
country: Canada
facility: Investigational Site Number 124018
city: Edmonton
country: Canada
facility: Investigational Site Number 124016
city: Hamilton
country: Canada
facility: Investigational Site Number 124014
city: Mirabel
country: Canada
facility: Investigational Site Number 124004
city: Mississauga
country: Canada
facility: Investigational Site Number 124026
city: Red Deer
country: Canada
facility: Investigational Site Number 124002
city: Sherbrooke
country: Canada
facility: Investigational Site Number 124013
city: Toronto
country: Canada
facility: Investigational Site Number 124011
city: Victoria
country: Canada
facility: Investigational Site Number 124010
city: Winnipeg
country: Canada
facility: Investigational Site Number 124022
city: Osorno
country: Chile
facility: Investigational Site Number 152014
city: Rancagua
country: Chile
facility: Investigational Site Number 152012
city: Santiago
country: Chile
facility: Investigational Site Number 152005
city: Santiago
country: Chile
facility: Investigational Site Number 152004
city: Santiago
country: Chile
facility: Investigational Site Number 152003
city: Santiago
country: Chile
facility: Investigational Site Number 152001
city: Santiago
country: Chile
facility: Investigational Site Number 152013
city: Santiago
country: Chile
facility: Investigational Site Number 152002
city: Santiago
country: Chile
facility: Investigational Site Number 152007
city: Santiago
country: Chile
facility: Investigational Site Number 152010
city: Temuco
country: Chile
facility: Investigational Site Number 152006
city: Valdivia
country: Chile
facility: Investigational Site Number 152009
city: Helsinki
country: Finland
facility: Investigational Site Number 246001
city: La Rochelle Cedex
country: France
facility: Investigational Site Number 250001
city: Le Creusot
country: France
facility: Investigational Site Number 250004
city: Mantes La Jolie
country: France
facility: Investigational Site Number 250005
city: Nantes
country: France
facility: Investigational Site Number 250002
city: Strasbourg
country: France
facility: Investigational Site Number 250009
city: Venissieux
country: France
facility: Investigational Site Number 250003
city: Künzing
country: Germany
facility: Investigational Site Number 276004
city: Neumünster
country: Germany
facility: Investigational Site Number 276003
city: Oberhausen
country: Germany
facility: Investigational Site Number 276008
city: Pirna
country: Germany
facility: Investigational Site Number 276009
city: Rehlingen-Siersburg
country: Germany
facility: Investigational Site Number 276007
city: Wangen
country: Germany
facility: Investigational Site Number 276005
city: Baja
country: Hungary
facility: Investigational Site Number 348006
city: Budapest
country: Hungary
facility: Investigational Site Number 348005
city: Budapest
country: Hungary
facility: Investigational Site Number 348003
city: Budapest
country: Hungary
facility: Investigational Site Number 348010
city: Budapest
country: Hungary
facility: Investigational Site Number 348009
city: Eger
country: Hungary
facility: Investigational Site Number 348002
city: Makó
country: Hungary
facility: Investigational Site Number 348001
city: Mosonmagyaróvár
country: Hungary
facility: Investigational Site Number 348008
city: Pápa
country: Hungary
facility: Investigational Site Number 348004
city: Sátorlaljaújhely
country: Hungary
facility: Investigational Site Number 348007
city: Acapulco
country: Mexico
facility: Investigational Site Number 484009
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484007
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484008
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484010
city: Mexico City
country: Mexico
facility: Investigational Site Number 484006
city: Monterrey
country: Mexico
facility: Investigational Site Number 484001
city: Monterrey
country: Mexico
facility: Investigational Site Number 484003
city: Pachuca
country: Mexico
facility: Investigational Site Number 484004
city: Matosinhos
country: Portugal
facility: Investigational Site Number 620007
city: Porto
country: Portugal
facility: Investigational Site Number 620004
city: Bacau
country: Romania
facility: Investigational Site Number 642008
city: Brasov
country: Romania
facility: Investigational Site Number 642009
city: Bucuresti
country: Romania
facility: Investigational Site Number 642003
city: Bucuresti
country: Romania
facility: Investigational Site Number 642001
city: Bucuresti
country: Romania
facility: Investigational Site Number 642002
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 642014
city: Deva
country: Romania
facility: Investigational Site Number 642006
city: Hunedoara
country: Romania
facility: Investigational Site Number 642011
city: Iasi
country: Romania
facility: Investigational Site Number 642015
city: Oradea
country: Romania
facility: Investigational Site Number 642013
city: Ploiesti
country: Romania
facility: Investigational Site Number 642010
city: Resita
country: Romania
facility: Investigational Site Number 642004
city: Targu Mures
country: Romania
facility: Investigational Site Number 642007
city: Timisoara
country: Romania
facility: Investigational Site Number 642012
city: Timisoara
country: Romania
facility: Investigational Site Number 642005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643010
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643007
city: Samara
country: Russian Federation
facility: Investigational Site Number 643011
city: Saratov
country: Russian Federation
facility: Investigational Site Number 643002
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643009
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643006
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643014
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643013
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643004
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643001
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number 643008
city: Ufa
country: Russian Federation
facility: Investigational Site Number 643016
city: Voronezh
country: Russian Federation
facility: Investigational Site Number 643005
city: Benoni
country: South Africa
facility: Investigational Site Number 710007
city: Bloemfontein
country: South Africa
facility: Investigational Site Number 710006
city: Bloemfontein
country: South Africa
facility: Investigational Site Number 710014
city: Boksburg
country: South Africa
facility: Investigational Site Number 710002
city: Cape Town
country: South Africa
facility: Investigational Site Number 710003
city: Cape Town
country: South Africa
facility: Investigational Site Number 710010
city: Johannesburg
country: South Africa
facility: Investigational Site Number 710001
city: Pretoria
country: South Africa
facility: Investigational Site Number 710005
city: Somerset West
country: South Africa
facility: Investigational Site Number 710012
city: Umkomaas
country: South Africa
facility: Investigational Site Number 710008
city: Barcelona
country: Spain
facility: Investigational Site Number 724005
city: Malaga
country: Spain
facility: Investigational Site Number 724003
city: Palma De Mallorca
country: Spain
facility: Investigational Site Number 724006
city: Sabadell
country: Spain
facility: Investigational Site Number 724001
city: Sevilla
country: Spain
facility: Investigational Site Number 724002
city: Valancia
country: Spain
facility: Investigational Site Number 724004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.