Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes Mellitus on Basal Plus Mealtime Insulin

Type 2 Diabetes Mellitus Clinical Trial

— EDITION I  

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 Plus Mealtime Insulin in Patients With Type 2 Diabetes Mellitus With a 6-month Safety Extension Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01499082
• Other study ID #: EFC11628
• Secondary ID: 2010-023769-23
• Status: Completed
• Phase: Phase 3
• Start date: December 2011
• Est. completion date: September 2013

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: - To compare the efficacy of insulin glargine new formulation and Lantus in terms of change in HbA1c from baseline to endpoint (scheduled month 6) in adult participants with type 2 diabetes mellitus Secondary Objectives: - To compare the efficacy of insulin glargine new formulation and Lantus in terms of occurrence of nocturnal Hypoglycemia

Description:

The maximum study duration was up to approximately 58 weeks per participant, 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 807
• Est. completion date: September 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 1 year on basal plus mealtime insulin and self-monitoring of blood glucose
• Any contraindication to use of insulin glargine as defined in the national product label
• Participants using human regular insulin as mealtime insulin in the last 3 months before screening visit
• Use of an insulin pump in the last 6 months before screening visit
• Initiation of new glucose-lowering agents and/or weight loss drugs 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.

Related Conditions & MeSH terms

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

Intervention

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 on top of mealtime insulin analogue. 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.
• Lantus (insulin glargine)
Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months on top of mealtime insulin analogue. Dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L (80 - 100 mg/dL).

Locations

Country	Name	City	State
Canada	Investigational Site Number 124024	Beamsville
Canada	Investigational Site Number 124025	Burlington
Canada	Investigational Site Number 124020	Calgary
Canada	Investigational Site Number 124023	Calgary
Canada	Investigational Site Number 124019	Chatham
Canada	Investigational Site Number 124018	Coquitlam
Canada	Investigational Site Number 124014	Hamilton
Canada	Investigational Site Number 124021	Hamilton
Canada	Investigational Site Number 124006	Laval
Canada	Investigational Site Number 124009	London
Canada	Investigational Site Number 124008	Mississauga
Canada	Investigational Site Number 124004	Montreal
Canada	Investigational Site Number 124015	Montreal
Canada	Investigational Site Number 124005	Oshawa
Canada	Investigational Site Number 124026	Quebec
Canada	Investigational Site Number 124002	Red Deer
Canada	Investigational Site Number 124007	Thornhill
Canada	Investigational Site Number 124001	Toronto
Canada	Investigational Site Number 124011	Toronto
Canada	Investigational Site Number 124010	Victoria
Canada	Investigational Site Number 124017	Ville St-Laurent
Canada	Investigational Site Number 124022	Winnipeg
Czechia	Investigational Site Number 203006	Beroun
Czechia	Investigational Site Number 203001	Breclav
Czechia	Investigational Site Number 203002	Hodonin
Czechia	Investigational Site Number 203009	Holesov
Czechia	Investigational Site Number 203003	Hradec Kralove
Czechia	Investigational Site Number 203007	Hranice
Czechia	Investigational Site Number 203004	Krnov
Czechia	Investigational Site Number 203010	Olomouc
Czechia	Investigational Site Number 203008	Praha 2
Czechia	Investigational Site Number 203005	Prostejov
Estonia	Investigational Site Number 233002	Pärnu
Estonia	Investigational Site Number 233001	Tallinn
Estonia	Investigational Site Number 233003	Tallinn
Estonia	Investigational Site Number 233004	Tallinn
Estonia	Investigational Site Number 233006	Tallinn
Estonia	Investigational Site Number 233005	Tartu
Finland	Investigational Site Number 246001	Helsinki
Finland	Investigational Site Number 246005	Kuopio
Finland	Investigational Site Number 246002	Oulu
France	Investigational Site Number 250004	La Rochelle Cedex
France	Investigational Site Number 250002	Strasbourg
Germany	Investigational Site Number 276006	Heidelberg
Germany	Investigational Site Number 276002	Riesa
Germany	Investigational Site Number 276003	Schwabenheim
Hungary	Investigational Site Number 348010	Baja
Hungary	Investigational Site Number 348004	Balatonfüred
Hungary	Investigational Site Number 348002	Budapest
Hungary	Investigational Site Number 348009	Budapest
Hungary	Investigational Site Number 348013	Budapest
Hungary	Investigational Site Number 348015	Budapest
Hungary	Investigational Site Number 348017	Budapest
Hungary	Investigational Site Number 348005	Debrecen
Hungary	Investigational Site Number 348008	Eger
Hungary	Investigational Site Number 348018	Gyula
Hungary	Investigational Site Number 348014	Makó
Hungary	Investigational Site Number 348012	Mosonmagyaróvár
Hungary	Investigational Site Number 348007	Nyiregyháza
Hungary	Investigational Site Number 348011	Sátorlaljaújhely
Hungary	Investigational Site Number 348003	Szeged
Hungary	Investigational Site Number 348006	Szombathely
Hungary	Investigational Site Number 348001	Zalaegerszeg
Latvia	Investigational Site Number 428006	Jekabpils
Latvia	Investigational Site Number 428005	Ogre
Latvia	Investigational Site Number 428001	Riga
Latvia	Investigational Site Number 428002	Riga
Latvia	Investigational Site Number 428004	Riga
Latvia	Investigational Site Number 428003	Sigulda
Mexico	Investigational Site Number 484007	Chihuahua
Mexico	Investigational Site Number 484001	Cuernavaca
Mexico	Investigational Site Number 484006	Guadalajara
Mexico	Investigational Site Number 484003	Monterrey
Mexico	Investigational Site Number 484004	Pachuca
Netherlands	Investigational Site Number 528009	Almelo
Netherlands	Investigational Site Number 528004	Eindhoven
Netherlands	Investigational Site Number 528007	Groningen
Netherlands	Investigational Site Number 528005	Hoogeveen
Netherlands	Investigational Site Number 528001	Hoorn
Netherlands	Investigational Site Number 528008	Leeuwarden
Netherlands	Investigational Site Number 528006	Utrecht
Netherlands	Investigational Site Number 528002	Venlo
Romania	Investigational Site Number 642001	Bacau
Romania	Investigational Site Number 642005	Bucuresti
Romania	Investigational Site Number 642006	Bucuresti
Romania	Investigational Site Number 642002	Cluj Napoca
Romania	Investigational Site Number 642004	Iasi
Romania	Investigational Site Number 642008	Iasi
Romania	Investigational Site Number 642003	Oradea
Romania	Investigational Site Number 642009	Targu Mures
Romania	Investigational Site Number 642007	Timisoara
South Africa	Investigational Site Number 710005	Alberton
South Africa	Investigational Site Number 710003	Johannesburg
South Africa	Investigational Site Number 710006	Lenasia
South Africa	Investigational Site Number 710002	Observatory
South Africa	Investigational Site Number 710001	Paarl
South Africa	Investigational Site Number 710008	Pretoria
South Africa	Investigational Site Number 710004	Somerset West
United States	Investigational Site Number 840076	Anaheim	California
United States	Investigational Site Number 840065	Ann Arbor	Michigan
United States	Investigational Site Number 840146	Asheville	North Carolina
United States	Investigational Site Number 840021	Austin	Texas
United States	Investigational Site Number 840081	Austin	Texas
United States	Investigational Site Number 840129	Austin	Texas
United States	Investigational Site Number 840078	Avon	Indiana
United States	Investigational Site Number 840089	Avon	Indiana
United States	Investigational Site Number 840097	Avon	Indiana
United States	Investigational Site Number 840098	Avon	Indiana
United States	Investigational Site Number 840100	Avon	Indiana
United States	Investigational Site Number 840036	Baltimore	Maryland
United States	Investigational Site Number 840155	Baltimore	Maryland
United States	Investigational Site Number 840043	Brick	New Jersey
United States	Investigational Site Number 840156	Chandler	Arizona
United States	Investigational Site Number 840143	Chaska	Minnesota
United States	Investigational Site Number 840039	Chattanooga	Tennessee
United States	Investigational Site Number 840035	Chesapeake	Virginia
United States	Investigational Site Number 840008	Cincinnati	Ohio
United States	Investigational Site Number 840114	Colorado Springs	Colorado
United States	Investigational Site Number 840136	Colorado Springs	Colorado
United States	Investigational Site Number 840106	Columbus	Ohio
United States	Investigational Site Number 840001	Dallas	Texas
United States	Investigational Site Number 840047	Dallas	Texas
United States	Investigational Site Number 840123	Dayton	Ohio
United States	Investigational Site Number 840049	Daytona Beach	Florida
United States	Investigational Site Number 840066	Dearborn	Michigan
United States	Investigational Site Number 840116	Des Moines	Iowa
United States	Investigational Site Number 840010	Draper	Utah
United States	Investigational Site Number 840068	Eagan	Minnesota
United States	Investigational Site Number 840133	Encino	California
United States	Investigational Site Number 840067	Fargo	North Dakota
United States	Investigational Site Number 840103	Flint	Michigan
United States	Investigational Site Number 840090	Fremont	Nebraska
United States	Investigational Site Number 840102	Glendale	Arizona
United States	Investigational Site Number 840062	Greenbrae	California
United States	Investigational Site Number 840079	Greer	South Carolina
United States	Investigational Site Number 840145	Hickory	North Carolina
United States	Investigational Site Number 840050	Hollywood	Florida
United States	Investigational Site Number 840016	Hot Springs	Arkansas
United States	Investigational Site Number 840082	Houston	Texas
United States	Investigational Site Number 840057	Huntington Beach	California
United States	Investigational Site Number 840120	Hurst	Texas
United States	Investigational Site Number 840052	Idaho Falls	Idaho
United States	Investigational Site Number 840009	Jacksonville	Florida
United States	Investigational Site Number 840011	Jacksonville	Florida
United States	Investigational Site Number 840086	Jacksonville	Florida
United States	Investigational Site Number 840126	Kalamazoo	Michigan
United States	Investigational Site Number 840053	Kalispell	Montana
United States	Investigational Site Number 840159	Knoxville	Tennessee
United States	Investigational Site Number 840059	La Jolla	California
United States	Investigational Site Number 840004	La Mesa	California
United States	Investigational Site Number 840058	Las Vegas	Nevada
United States	Investigational Site Number 840055	Lawrenceville	Georgia
United States	Investigational Site Number 840080	Lexington	Kentucky
United States	Investigational Site Number 840015	Little Rock	Arkansas
United States	Investigational Site Number 840124	Little Rock	Arkansas
United States	Investigational Site Number 840092	Longmont	Colorado
United States	Investigational Site Number 840119	Maumee	Ohio
United States	Investigational Site Number 840020	McHenry	Illinois
United States	Investigational Site Number 840083	Medford	Oregon
United States	Investigational Site Number 840122	Mentor	Ohio
United States	Investigational Site Number 840018	Milwaukee	Wisconsin
United States	Investigational Site Number 840085	Minneapolis	Minnesota
United States	Investigational Site Number 840099	Mission Hills	California
United States	Investigational Site Number 840117	Nampa	Idaho
United States	Investigational Site Number 840023	New Port Richey	Florida
United States	Investigational Site Number 840041	Norfolk	Virginia
United States	Investigational Site Number 840074	Norfolk	Virginia
United States	Investigational Site Number 840112	Norfolk	Virginia
United States	Investigational Site Number 840012	Ocoee	Florida
United States	Investigational Site Number 840060	Ogden	Utah
United States	Investigational Site Number 840091	Omaha	Nebraska
United States	Investigational Site Number 840042	Paducah	Kentucky
United States	Investigational Site Number 840148	Palm Harbor	Florida
United States	Investigational Site Number 840107	Palm Springs	California
United States	Investigational Site Number 840071	Phoenix	Arizona
United States	Investigational Site Number 840084	Portland	Oregon
United States	Investigational Site Number 840048	Rapid City	South Dakota
United States	Investigational Site Number 840104	Richmond	Virginia
United States	Investigational Site Number 840034	Rockville	Maryland
United States	Investigational Site Number 840005	San Diego	California
United States	Investigational Site Number 840032	Searcy	Arkansas
United States	Investigational Site Number 840022	Southfield	Michigan
United States	Investigational Site Number 840019	Springfield	Illinois
United States	Investigational Site Number 840121	Sun City	Arizona
United States	Investigational Site Number 840070	Tempe	Arizona
United States	Investigational Site Number 840152	Toms River	New Jersey
United States	Investigational Site Number 840013	Tustin	California
United States	Investigational Site Number 840007	Uniontown	Pennsylvania
United States	Investigational Site Number 840127	Vincennes	Indiana
United States	Investigational Site Number 840002	Walnut Creek	California
United States	Investigational Site Number 840003	Wichita	Kansas
United States	Investigational Site Number 840075	Williamsburg	Virginia
United States	Investigational Site Number 840045	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Estonia,  Finland,  France,  Germany,  Hungary,  Latvia,  Mexico,  Netherlands,  Romania,  South Africa, 

References & Publications (1)

Riddle MC, Bolli GB, Ziemen M, Muehlen-Bartmer I, Bizet F, Home PD; EDITION 1 Study Investigators. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglyc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Month 6 Up to Month 9
Primary	Change in HbA1c From Baseline to Month 6 Endpoint		Baseline, Month 6
Secondary	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 millimoles per liter (mmol/L) (70 milligram per deciliter [mg/dL]).	Week 9 Up to Month 6
Secondary	Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint	Pre-injection 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.	Baseline, Month 6
Secondary	Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint	Pre-injection SMPG was measured within 30 minutes prior to the injection of the study drug. Variability was assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 3 SMPG measured during the 7 days preceding the assessment visit.	Baseline, Month 6
Secondary	Percentage of Participants With HbA1c <7% at Month 6 Endpoint		Month 6
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint		Baseline, Month 6
Secondary	Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint		Month 6
Secondary	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.	Baseline, Month 6
Secondary	Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint		Baseline, Month 6
Secondary	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.	Baseline, Month 6
Secondary	Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up 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