Clinical trial NCT02320721: Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Older Patients With Type2 Diabetes Insufficiently Controlled on Their Current Antidiabetic Medications
Official title: A Randomized, Open-label, 2-arm Parallel-group, Multicenter, 26-week Study Assessing the Safety and Efficacy of H0E901-U300 Versus Lantus in Older Patients With Type 2 Diabetes Inadequately Controlled on Antidiabetic Regimens Either Including no Insulin, or With Basal Insulin as Their Only Insulin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2014-12-19
Enrollment: 1014
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To demonstrate the non-inferiority of H0E901-U300 to Lantus, in change of glycated hemoglobin A1c (HbA1c).

Secondary Objectives:

To demonstrate the superiority of H0E901-U300 in comparison with Lantus in:

* Percentage of participants with at least one severe and/or confirmed (by plasma glucose ≤70mg/dL \[3.9mmol/L\]) hypoglycemia event from 22:00 to 08:59 next morning
* Percentage of participants with at least one nocturnal (from 00:00-05:59) severe and/or confirmed (≤70mg/dL \[3.9mmol/L\]) hypoglycemia event
* Percentage of participants with at least one severe and/or confirmed (by plasma glucose ≤70mg/dL \[3.9mmol/L\]) hypoglycemia event occurring at any time of day
* HbA1c change

Detailed description: The study consisted of a 4-week screening period, a 26-week treatment period comparing HOE901-U300 to Lantus, and a 2-day safety follow-up period.

Eligibility criteria: Inclusion criteria:

* Participants ≥65 years old with type 2 diabetes mellitus, inadequately controlled on antidiabetic regimens either including no insulin, or with basal insulin as their only insulin.
* Signed informed consent.

Exclusion criteria:

* HbA1c at screening visit:

  * \<7.0% or \>10.0% for participants taking basal insulin.
  * \<7.5% or \>11.0% for insulin-naïve participants.
* History of type 2 diabetes mellitus for less than 1 year before screening.
* Participants not on stable basal insulin dose (±10% in the last 8 weeks prior to screening visit).
* Change in dose of antidiabetic treatment or initiation of new glucose-lowering medications in the last 8 weeks prior to screening.
* Chronic (\>10 days continuous use in previous 6 months) use of bolus insulin injections, whether given separately or as part of a combination with basal insulin, e.g. premix insulin; For insulin-naïve individuals: current or previous insulin use except for a maximum of 10 consecutive days (e.g. acute illness, surgery) during the last year prior to screening.
* Cognitive disorder and dementia assessed clinically and by Mini-Mental State Examination (MMSE) score \<24, or any neurologic disorder that would likely affect the participant's ability to follow the study procedure. The participant would be eligible despite an MMSE score \<24 if the investigator determined that the low score reflected educational or cultural background and not dementia as long as the participant was otherwise able to meet the study requirements.
* Participants who had end-stage renal disease (\<15 mL/min/1.73m\^2, per estimated Glomerular filtration rate (eGFR) measurement by Modification of Diet in Renal Disease (MDRD).

The above information was 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 Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (22:00 to 08:59 Hours Next Morning) During 26-Week Randomized Period
timeFrame: Baseline up to Week 26
measure: Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (00:00 to 05:59 Hours) During 26-Week Randomized Period
timeFrame: Baseline up to Week 26
measure: Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia Occurring at Any Time of the Day During 26-Week Randomized Period
timeFrame: Baseline up to Week 26
measure: Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period
timeFrame: Baseline up to Week 26
measure: Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period
timeFrame: Baseline up to Week 26
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment
timeFrame: Baseline up to Week 26
Other outcomes:
measure: Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment
timeFrame: Baseline up to Week 26
measure: Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment
timeFrame: Baseline up to Week 26
Locations:
city: Saraland
country: United States
facility: Investigational Site Number 840058
state: Alabama
city: Fresno
country: United States
facility: Investigational Site Number 840019
state: California
city: Fresno
country: United States
facility: Investigational Site Number 840021
state: California
city: Greenbrae
country: United States
facility: Investigational Site Number 840040
state: California
city: Huntington Park
country: United States
facility: Investigational Site Number 840070
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840064
state: California
city: Norwalk
country: United States
facility: Investigational Site Number 840031
state: California
city: Oakland
country: United States
facility: Investigational Site Number 840065
state: California
city: Orange
country: United States
facility: Investigational Site Number 840050
state: California
city: Simi Valley
country: United States
facility: Investigational Site Number 840036
state: California
city: Temecula
country: United States
facility: Investigational Site Number 840003
state: California
city: Walnut Creek
country: United States
facility: Investigational Site Number 840062
state: California
city: Longmont
country: United States
facility: Investigational Site Number 840027
state: Colorado
city: Bradenton
country: United States
facility: Investigational Site Number 840030
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840010
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840035
state: Florida
city: New Port Richey
country: United States
facility: Investigational Site Number 840014
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 840051
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 840056
state: Florida
city: Saint Petersburg
country: United States
facility: Investigational Site Number 840007
state: Florida
city: Roswell
country: United States
facility: Investigational Site Number 840041
state: Georgia
city: Statesboro
country: United States
facility: Investigational Site Number 840053
state: Georgia
city: Woodstock
country: United States
facility: Investigational Site Number 840042
state: Georgia
city: Arlington Heights
country: United States
facility: Investigational Site Number 840005
state: Illinois
city: Peoria
country: United States
facility: Investigational Site Number 840004
state: Illinois
city: Springfield
country: United States
facility: Investigational Site Number 840029
state: Illinois
city: Avon
country: United States
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state: Indiana
city: Avon
country: United States
facility: Investigational Site Number 840023
state: Indiana
city: Evansville
country: United States
facility: Investigational Site Number 840039
state: Indiana
city: Muncie
country: United States
facility: Investigational Site Number 840006
state: Indiana
city: Des Moines
country: United States
facility: Investigational Site Number 840026
state: Iowa
city: West Des Moines
country: United States
facility: Investigational Site Number 840033
state: Iowa
city: Overland Park
country: United States
facility: Investigational Site Number 840032
state: Kansas
city: Metairie
country: United States
facility: Investigational Site Number 840069
state: Louisiana
city: Flint
country: United States
facility: Investigational Site Number 840020
state: Michigan
city: Nashua
country: United States
facility: Investigational Site Number 840037
state: New Hampshire
city: New York
country: United States
facility: Investigational Site Number 840018
state: New York
city: Asheville
country: United States
facility: Investigational Site Number 840048
state: North Carolina
city: Charlotte
country: United States
facility: Investigational Site Number 840009
state: North Carolina
city: Greensboro
country: United States
facility: Investigational Site Number 840011
state: North Carolina
city: Greenville
country: United States
facility: Investigational Site Number 840047
state: North Carolina
city: Salisbury
country: United States
facility: Investigational Site Number 840016
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 840012
state: North Carolina
city: Fargo
country: United States
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state: North Dakota
city: Cincinnati
country: United States
facility: Investigational Site Number 840072
state: Ohio
city: Wadsworth
country: United States
facility: Investigational Site Number 840054
state: Ohio
city: Bend
country: United States
facility: Investigational Site Number 840067
state: Oregon
city: Corvallis
country: United States
facility: Investigational Site Number 840057
state: Oregon
city: Feasterville
country: United States
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state: Pennsylvania
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Greenville
country: United States
facility: Investigational Site Number 840059
state: South Carolina
city: Greer
country: United States
facility: Investigational Site Number 840015
state: South Carolina
city: Chattanooga
country: United States
facility: Investigational Site Number 840002
state: Tennessee
city: Chattanooga
country: United States
facility: Investigational Site Number 840046
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 840034
state: Tennessee
city: Arlington
country: United States
facility: Investigational Site Number 840055
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840001
state: Texas
city: Irving
country: United States
facility: Investigational Site Number 840024
state: Texas
city: North Richland Hills
country: United States
facility: Investigational Site Number 840061
state: Texas
city: Richmond
country: United States
facility: Investigational Site Number 840028
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840063
state: Texas
city: Saint George
country: United States
facility: Investigational Site Number 840038
state: Utah
city: Federal Way
country: United States
facility: Investigational Site Number 840025
state: Washington
city: Bridgeport
country: United States
facility: Investigational Site Number 840060
state: West Virginia
city: Caba
country: Argentina
facility: Investigational Site Number 032001
city: Caba
country: Argentina
facility: Investigational Site Number 032002
city: Capital Federal
country: Argentina
facility: Investigational Site Number 032006
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Investigational Site Number 032004
city: Mar Del Plata
country: Argentina
facility: Investigational Site Number 032003
city: Box Hill
country: Australia
facility: Investigational Site Number 036002
city: Fitzroy
country: Australia
facility: Investigational Site Number 036004
city: Geelong
country: Australia
facility: Investigational Site Number 036001
city: Herston
country: Australia
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city: Brampton
country: Canada
facility: Investigational Site Number 124003
city: Burlington
country: Canada
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city: Chatham
country: Canada
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city: Mirabel
country: Canada
facility: Investigational Site Number 124010
city: Montreal
country: Canada
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city: Sainte-Foy
country: Canada
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city: Thornhill
country: Canada
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city: Toronto
country: Canada
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city: Vancouver
country: Canada
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city: Vancouver
country: Canada
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city: Armenia
country: Colombia
facility: Investigational Site Number 170004
city: Barranquilla
country: Colombia
facility: Investigational Site Number 170007
city: Bogota
country: Colombia
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city: Bogota
country: Colombia
facility: Investigational Site Number 170005
city: Manizales
country: Colombia
facility: Investigational Site Number 170003
city: Lyon
country: France
facility: Investigational Site Number 250004
city: Nantes Cedex 01
country: France
facility: Investigational Site Number 250006
city: Poitiers Cedex
country: France
facility: Investigational Site Number 250005
city: Dresden
country: Germany
facility: Investigational Site Number 276004
city: Essen
country: Germany
facility: Investigational Site Number 276003
city: München
country: Germany
facility: Investigational Site Number 276001
city: Potsdam
country: Germany
facility: Investigational Site Number 276005
city: Saarlouis
country: Germany
facility: Investigational Site Number 276002
city: Balatonfüred
country: Hungary
facility: Investigational Site Number 348004
city: Budapest
country: Hungary
facility: Investigational Site Number 348001
city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Csongrád
country: Hungary
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city: Debrecen
country: Hungary
facility: Investigational Site Number 348009
city: Gyula
country: Hungary
facility: Investigational Site Number 348002
city: Bologna
country: Italy
facility: Investigational Site Number 380004
city: Chieti
country: Italy
facility: Investigational Site Number 380005
city: Genova
country: Italy
facility: Investigational Site Number 380003
city: Milano
country: Italy
facility: Investigational Site Number 380002
city: Milano
country: Italy
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city: Adachi-Ku
country: Japan
facility: Investigational Site Number 392008
city: Atsugi-Shi
country: Japan
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city: Kamakura-Shi
country: Japan
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country: Japan
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city: Sakado-Shi
country: Japan
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country: Japan
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city: Sendai-Shi
country: Japan
facility: Investigational Site Number 392012
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410005
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410002
city: Seoul
country: Korea, Republic of
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city: Wonju
country: Korea, Republic of
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city: Aguascalientes
country: Mexico
facility: Investigational Site Number 484002
city: Cuernavaca
country: Mexico
facility: Investigational Site Number 484004
city: Guadalajara
country: Mexico
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city: Monterrey
country: Mexico
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city: Arequipa
country: Peru
facility: Investigational Site Number 604004
city: Ica
country: Peru
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city: Lima
country: Peru
facility: Investigational Site Number 604002
city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Piura
country: Peru
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city: Lublin
country: Poland
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city: Szczecin
country: Poland
facility: Investigational Site Number 616004
city: Warszawa
country: Poland
facility: Investigational Site Number 616003
city: Warszawa
country: Poland
facility: Investigational Site Number 616002
city: Zabrze
country: Poland
facility: Investigational Site Number 616001
city: Bacau
country: Romania
facility: Investigational Site Number 642006
city: Bucuresti
country: Romania
facility: Investigational Site Number 642001
city: Constanta
country: Romania
facility: Investigational Site Number 642007
city: Oradea
country: Romania
facility: Investigational Site Number 642004
city: Sibiu
country: Romania
facility: Investigational Site Number 642005
city: Targu Mures
country: Romania
facility: Investigational Site Number 642002
city: Targu Mures
country: Romania
facility: Investigational Site Number 642003
city: Alzira
country: Spain
facility: Investigational Site Number 724004
city: Badalona
country: Spain
facility: Investigational Site Number 724001
city: El Ferrol
country: Spain
facility: Investigational Site Number 724002
city: La Coruña
country: Spain
facility: Investigational Site Number 724008
city: Málaga
country: Spain
facility: Investigational Site Number 724006
city: Quart De Poblet
country: Spain
facility: Investigational Site Number 724007
city: Sanlúcar De Barrameda
country: Spain
facility: Investigational Site Number 724003
city: Sevilla
country: Spain
facility: Investigational Site Number 724005
city: Göteborg
country: Sweden
facility: Investigational Site Number 752002
city: Härnösand
country: Sweden
facility: Investigational Site Number 752004
city: Rättvik
country: Sweden
facility: Investigational Site Number 752003
city: Västra Frölunda
country: Sweden
facility: Investigational Site Number 752001
city: Belfast
country: United Kingdom
facility: Investigational Site Number 826003
city: Belfast
country: United Kingdom
facility: Investigational Site Number 826005
city: Bristol
country: United Kingdom
facility: Investigational Site Number 826001
city: Redhill
country: United Kingdom
facility: Investigational Site Number 826004
city: Rotherham
country: United Kingdom
facility: Investigational Site Number 826006
city: Swansea
country: United Kingdom
facility: Investigational Site Number 826002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Ritzel R, Harris SB, Baron H, Florez H, Roussel R, Espinasse M, Muehlen-Bartmer I, Zhang N, Bertolini M, Brulle-Wohlhueter C, Munshi M, Bolli GB. A Randomized Controlled Trial Comparing Efficacy and Safety of Insulin Glargine 300 Units/mL Versus 100 Units/mL in Older People With Type 2 Diabetes: Results From the SENIOR Study. Diabetes Care. 2018 Aug;41(8):1672-1680. doi: 10.2337/dc18-0168. Epub 2018 Jun 12.