Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Older Patients With Type2 Diabetes Insufficiently Controlled on Their Current Antidiabetic Medications

Type 2 Diabetes Mellitus Clinical Trial

— SENIOR  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02320721
• Other study ID #: EFC13799
• Secondary ID: 2014-002399-10U1
• Status: Completed
• Phase: Phase 3
• Start date: January 2015
• Est. completion date: May 2016

Study information

• Verified date: April 2020
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1014
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Insulin Glargine (HOE901 - U300)
Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 90 to 130 mg/dL (5.0 to 7.2 mmol/L).
• Insulin Glargine (HOE901 - U100)
Self-administered by SC injection in the evening using a pre-filled pen. Dose titration to achieve fasting SMPG from 90 to 130 mg/dL (5.0 to 7.2 mmol/L).
• Background therapy
Non-insulin anti-diabetic drugs with the exception of thiazolidinediones.

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032001	Caba
Argentina	Investigational Site Number 032002	Caba
Argentina	Investigational Site Number 032006	Capital Federal
Argentina	Investigational Site Number 032004	Ciudad Autonoma De Buenos Aire
Argentina	Investigational Site Number 032003	Mar Del Plata
Australia	Investigational Site Number 036002	Box Hill
Australia	Investigational Site Number 036004	Fitzroy
Australia	Investigational Site Number 036001	Geelong
Australia	Investigational Site Number 036003	Herston
Canada	Investigational Site Number 124003	Brampton
Canada	Investigational Site Number 124005	Burlington
Canada	Investigational Site Number 124008	Chatham
Canada	Investigational Site Number 124010	Mirabel
Canada	Investigational Site Number 124009	Montreal
Canada	Investigational Site Number 124006	Sainte-Foy
Canada	Investigational Site Number 124004	Thornhill
Canada	Investigational Site Number 124002	Toronto
Canada	Investigational Site Number 124001	Vancouver
Canada	Investigational Site Number 124007	Vancouver
Colombia	Investigational Site Number 170004	Armenia
Colombia	Investigational Site Number 170007	Barranquilla
Colombia	Investigational Site Number 170001	Bogota
Colombia	Investigational Site Number 170005	Bogota
Colombia	Investigational Site Number 170003	Manizales
France	Investigational Site Number 250004	Lyon
France	Investigational Site Number 250006	Nantes Cedex 01
France	Investigational Site Number 250005	Poitiers Cedex
Germany	Investigational Site Number 276004	Dresden
Germany	Investigational Site Number 276003	Essen
Germany	Investigational Site Number 276001	München
Germany	Investigational Site Number 276005	Potsdam
Germany	Investigational Site Number 276002	Saarlouis
Hungary	Investigational Site Number 348004	Balatonfüred
Hungary	Investigational Site Number 348001	Budapest
Hungary	Investigational Site Number 348003	Budapest
Hungary	Investigational Site Number 348005	Budapest
Hungary	Investigational Site Number 348007	Budapest
Hungary	Investigational Site Number 348008	Csongrád
Hungary	Investigational Site Number 348009	Debrecen
Hungary	Investigational Site Number 348002	Gyula
Italy	Investigational Site Number 380004	Bologna
Italy	Investigational Site Number 380005	Chieti
Italy	Investigational Site Number 380003	Genova
Italy	Investigational Site Number 380001	Milano
Italy	Investigational Site Number 380002	Milano
Japan	Investigational Site Number 392008	Adachi-Ku
Japan	Investigational Site Number 392003	Atsugi-Shi
Japan	Investigational Site Number 392002	Kamakura-Shi
Japan	Investigational Site Number 392010	Sagamihara-Shi
Japan	Investigational Site Number 392004	Sakado-Shi
Japan	Investigational Site Number 392013	Sapporo-Shi
Japan	Investigational Site Number 392012	Sendai-Shi
Korea, Republic of	Investigational Site Number 410001	Seoul
Korea, Republic of	Investigational Site Number 410002	Seoul
Korea, Republic of	Investigational Site Number 410003	Seoul
Korea, Republic of	Investigational Site Number 410005	Seoul
Korea, Republic of	Investigational Site Number 410004	Wonju
Mexico	Investigational Site Number 484002	Aguascalientes
Mexico	Investigational Site Number 484004	Cuernavaca
Mexico	Investigational Site Number 484001	Guadalajara
Mexico	Investigational Site Number 484003	Monterrey
Peru	Investigational Site Number 604004	Arequipa
Peru	Investigational Site Number 604007	Ica
Peru	Investigational Site Number 604001	Lima
Peru	Investigational Site Number 604002	Lima
Peru	Investigational Site Number 604005	Lima
Peru	Investigational Site Number 604006	Lima
Peru	Investigational Site Number 604003	Piura
Poland	Investigational Site Number 616005	Lublin
Poland	Investigational Site Number 616004	Szczecin
Poland	Investigational Site Number 616002	Warszawa
Poland	Investigational Site Number 616003	Warszawa
Poland	Investigational Site Number 616001	Zabrze
Romania	Investigational Site Number 642006	Bacau
Romania	Investigational Site Number 642001	Bucuresti
Romania	Investigational Site Number 642007	Constanta
Romania	Investigational Site Number 642004	Oradea
Romania	Investigational Site Number 642005	Sibiu
Romania	Investigational Site Number 642002	Targu Mures
Romania	Investigational Site Number 642003	Targu Mures
Spain	Investigational Site Number 724004	Alzira
Spain	Investigational Site Number 724001	Badalona
Spain	Investigational Site Number 724002	El Ferrol
Spain	Investigational Site Number 724008	La Coruña
Spain	Investigational Site Number 724006	Málaga
Spain	Investigational Site Number 724007	Quart De Poblet
Spain	Investigational Site Number 724003	Sanlúcar De Barrameda
Spain	Investigational Site Number 724005	Sevilla
Sweden	Investigational Site Number 752002	Göteborg
Sweden	Investigational Site Number 752004	Härnösand
Sweden	Investigational Site Number 752003	Rättvik
Sweden	Investigational Site Number 752001	Västra Frölunda
United Kingdom	Investigational Site Number 826003	Belfast
United Kingdom	Investigational Site Number 826005	Belfast
United Kingdom	Investigational Site Number 826001	Bristol
United Kingdom	Investigational Site Number 826004	Redhill
United Kingdom	Investigational Site Number 826006	Rotherham
United Kingdom	Investigational Site Number 826002	Swansea
United States	Investigational Site Number 840055	Arlington	Texas
United States	Investigational Site Number 840005	Arlington Heights	Illinois
United States	Investigational Site Number 840048	Asheville	North Carolina
United States	Investigational Site Number 840013	Avon	Indiana
United States	Investigational Site Number 840023	Avon	Indiana
United States	Investigational Site Number 840067	Bend	Oregon
United States	Investigational Site Number 840030	Bradenton	Florida
United States	Investigational Site Number 840060	Bridgeport	West Virginia
United States	Investigational Site Number 840009	Charlotte	North Carolina
United States	Investigational Site Number 840002	Chattanooga	Tennessee
United States	Investigational Site Number 840046	Chattanooga	Tennessee
United States	Investigational Site Number 840072	Cincinnati	Ohio
United States	Investigational Site Number 840057	Corvallis	Oregon
United States	Investigational Site Number 840001	Dallas	Texas
United States	Investigational Site Number 840026	Des Moines	Iowa
United States	Investigational Site Number 840039	Evansville	Indiana
United States	Investigational Site Number 840022	Fargo	North Dakota
United States	Investigational Site Number 840045	Feasterville	Pennsylvania
United States	Investigational Site Number 840025	Federal Way	Washington
United States	Investigational Site Number 840020	Flint	Michigan
United States	Investigational Site Number 840019	Fresno	California
United States	Investigational Site Number 840021	Fresno	California
United States	Investigational Site Number 840040	Greenbrae	California
United States	Investigational Site Number 840011	Greensboro	North Carolina
United States	Investigational Site Number 840047	Greenville	North Carolina
United States	Investigational Site Number 840059	Greenville	South Carolina
United States	Investigational Site Number 840015	Greer	South Carolina
United States	Investigational Site Number 840070	Huntington Park	California
United States	Investigational Site Number 840024	Irving	Texas
United States	Investigational Site Number 840034	Knoxville	Tennessee
United States	Investigational Site Number 840027	Longmont	Colorado
United States	Investigational Site Number 840064	Los Angeles	California
United States	Investigational Site Number 840069	Metairie	Louisiana
United States	Investigational Site Number 840010	Miami	Florida
United States	Investigational Site Number 840035	Miami	Florida
United States	Investigational Site Number 840006	Muncie	Indiana
United States	Investigational Site Number 840037	Nashua	New Hampshire
United States	Investigational Site Number 840014	New Port Richey	Florida
United States	Investigational Site Number 840018	New York	New York
United States	Investigational Site Number 840061	North Richland Hills	Texas
United States	Investigational Site Number 840031	Norwalk	California
United States	Investigational Site Number 840065	Oakland	California
United States	Investigational Site Number 840051	Ocoee	Florida
United States	Investigational Site Number 840050	Orange	California
United States	Investigational Site Number 840032	Overland Park	Kansas
United States	Investigational Site Number 840056	Palm Harbor	Florida
United States	Investigational Site Number 840004	Peoria	Illinois
United States	Investigational Site Number 840017	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840028	Richmond	Texas
United States	Investigational Site Number 840041	Roswell	Georgia
United States	Investigational Site Number 840038	Saint George	Utah
United States	Investigational Site Number 840007	Saint Petersburg	Florida
United States	Investigational Site Number 840016	Salisbury	North Carolina
United States	Investigational Site Number 840063	San Antonio	Texas
United States	Investigational Site Number 840058	Saraland	Alabama
United States	Investigational Site Number 840036	Simi Valley	California
United States	Investigational Site Number 840029	Springfield	Illinois
United States	Investigational Site Number 840053	Statesboro	Georgia
United States	Investigational Site Number 840003	Temecula	California
United States	Investigational Site Number 840054	Wadsworth	Ohio
United States	Investigational Site Number 840062	Walnut Creek	California
United States	Investigational Site Number 840033	West Des Moines	Iowa
United States	Investigational Site Number 840012	Wilmington	North Carolina
United States	Investigational Site Number 840042	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Colombia,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Romania,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment	Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose =3.9 mmol/L [70 mg/dL]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose =3.9 mmol/L).	Baseline up to Week 26
Other	Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment	Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose =3.9 mmol/L [70 mg/dL]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose =3.9 mmol/L).	Baseline up to Week 26
Primary	Change in HbA1c From Baseline to Week 26	Adjusted least square (LS) means were obtained from analysis of covariance (ANCOVA) after multiple imputation of missing data including post baseline HbA1c data during the 26-week randomized period.	Baseline, Week 26
Secondary	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	Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 =3.9 mmol/L (70 mg/dL).	Baseline up to Week 26
Secondary	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	Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 =3.9 mmol/L (70 mg/dL).	Baseline up to Week 26
Secondary	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	Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 =3.9 mmol/L (70 mg/dL).	Baseline up to Week 26
Secondary	Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period	Participants without any available HbA1c assessment at Week 26 were considered as non-responders in the analyses.	Baseline up to Week 26
Secondary	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	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 =3.9 mmol/L (70 mg/dL).	Baseline up to Week 26
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26	Adjusted LS means from multiple imputation approach including post baseline values during the 26-week randomized period.	Baseline, Week 26
Secondary	Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26	WHO-5 well-being index evaluates positive psychological well-being during the past 2 weeks and consists of 5 questions, each rated on a 6-point Likert scale from 0 (not present) to 5 (constantly present). Total raw score was transformed into a percentage score ranging from 0 (worst possible quality of life) to 100 (best possible quality of life).	Baseline, Week 26
Secondary	Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment	Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after Week 14) values were used to determine the requirement of rescue medication. Threshold values at Week 14: FPG >200 mg/dL (11 mmol/L), or HbA1c >8.5%.	Baseline up to Week 26