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

Type 2 Diabetes Mellitus Clinical Trial

— EDITION II  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01499095
• Other study ID #: EFC11629
• Secondary ID: 2010-023770-39U1
• Status: Completed
• Phase: Phase 3
• Start date: December 2011
• Est. completion date: November 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 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 811
• Est. completion date: November 2013
• Est. primary completion date: April 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 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.

Related Conditions & MeSH terms

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

Intervention

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).
• 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.

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

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Finland,  France,  Germany,  Hungary,  Mexico,  Portugal,  Romania,  Russian Federation,  South Africa,  Spain, 

References & Publications (1)

Yki-Järvinen 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: g — 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. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Month 6 up to Month 9
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
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. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Secondary	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
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. Only measurements performed before initiation of rescue therapy were considered in the analysis.	Baseline, Month 6
Secondary	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