Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes on Non-insulin Antidiabetic Therapy

Type 2 Diabetes Mellitus Clinical Trial

— EDITION III  

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® in Insulin-Naïve Patients With Type 2 Diabetes Mellitus Not Adequately Controlled With Non-Insulin Antihyperglycemic Drugs With a 6-month Safety Extension Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01676220
• Other study ID #: EFC12347
• Secondary ID: 2012-000146-35U1
• Status: Completed
• Phase: Phase 3
• First received: August 28, 2012
• Last updated: May 28, 2015
• Start date: August 2012
• Est. completion date: March 2014

Study information

• Verified date: May 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To compare the efficacy of a new formulation of insulin glargine and Lantus in terms of change of HbA1c from baseline to endpoint (scheduled at Month 6, Week 26) in participants with type 2 diabetes mellitus

Secondary Objectives:

To compare a new formulation of insulin glargine and Lantus in terms of:

• occurrence of nocturnal hypoglycemia

Description:

The maximum study duration was up to approximately 54 weeks per participant, consisting of:

• Up to 2 week screening period; it can be exceptionally extended of up to one additional week

• 6-month comparative efficacy and safety treatment period

• 6-month comparative safety extension period

• 2-day post-treatment safety follow-up period

Recruitment information / eligibility

• Status: Completed
• Enrollment: 878
• Est. completion date: March 2014
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Adult participants with type 2 diabetes mellitus inadequately controlled with non-insulin antihyperglycemic drug(s);

• Signed written informed consent.

Exclusion criteria:

• HbA1c less than (<) 7.0% (< 53 millimole per mole [mmol/mol]) or greater than (>) 11% (> 97 mmol/mol)

• History of type 2 diabetes mellitus for less than 1 year before screening

• Less than 6 months before screening with non-insulin antihyperglycemic treatment

• Change in dose of non-insulin antihyperglycemic treatment in the last 3 month before screening

• Initiation of new glucose-lowering medications and/or weight loss drug in the last 3 months before screening visit and/or initiation of Glucagon-like peptide-1 (GLP-1) receptor agonist in the last 6 months before screening visit

• Participants receiving only non-insulin antihyperglycemic drugs not approved for combination with insulin according to local labeling/local treatment guidelines and/or sulfonylurea or glinide (Note: non-insulin antihyperglycemic drugs not approved for combination with insulin, sulfonylurea and glinide are to be discontinued at baseline)

• Current or previous insulin use except for a maximum of 8 consecutive days (for example, acute illness, surgery) during the last year prior to screening

• Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (for example, laser, surgical treatment or injectable drugs) during the study period

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

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 non-insulin antihyperglycemic drug(s). Dose titration seeking fasting plasma glucose 4.4-5.6 millimole per liter (mmol/L) (80 - 100 milligram per deciliter [mg/dL]).
• Lantus (insulin glargine)
Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months on top of non-insulin antihyperglycemic drug(s). Dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L (80 - 100 mg/dL).

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number 100205	Blagoevgrad
Bulgaria	Investigational Site Number 100203	Byala
Bulgaria	Investigational Site Number 100201	Plovdiv
Bulgaria	Investigational Site Number 100204	Plovdiv
Bulgaria	Investigational Site Number 100206	Sofia
Canada	Investigational Site Number 124204	Brampton
Canada	Investigational Site Number 124211	Etobicoke
Canada	Investigational Site Number 124208	Laval
Canada	Investigational Site Number 124214	London
Canada	Investigational Site Number 124210	Montreal
Canada	Investigational Site Number 124218	Montreal
Canada	Investigational Site Number 124206	Pointe-Claire
Canada	Investigational Site Number 124219	Sherbrooke
Canada	Investigational Site Number 124201	Thornhill
Canada	Investigational Site Number 124209	Thornhill
Canada	Investigational Site Number 124212	Toronto
Canada	Investigational Site Number 124216	Ville St-Laurent
Czech Republic	Investigational Site Number 203201	Brno
Czech Republic	Investigational Site Number 203205	Brno
Czech Republic	Investigational Site Number 203204	Havirov
Czech Republic	Investigational Site Number 203203	Praha 10
Czech Republic	Investigational Site Number 203202	Praha 8
Denmark	Investigational Site Number 208205	Ålborg
Denmark	Investigational Site Number 208203	Esbjerg
Denmark	Investigational Site Number 208209	Hellerup
Denmark	Investigational Site Number 208202	Herlev
Denmark	Investigational Site Number 208206	Hvidovre
Denmark	Investigational Site Number 208207	København Nv
Denmark	Investigational Site Number 208210	Kolding
Denmark	Investigational Site Number 208201	Odense C
Denmark	Investigational Site Number 208204	Viborg
Estonia	Investigational Site Number 233204	Tallinn
Estonia	Investigational Site Number 233203	Tartu
Estonia	Investigational Site Number 233205	Tartu
Finland	Investigational Site Number 246208	Helsinki
Finland	Investigational Site Number 246202	Kokkola
Finland	Investigational Site Number 246207	Oulu
Finland	Investigational Site Number 246206	Tampere
Finland	Investigational Site Number 246205	Turku
Hungary	Investigational Site Number 348205	Balassagyarmat
Hungary	Investigational Site Number 348201	Budapest
Hungary	Investigational Site Number 348207	Budapest
Hungary	Investigational Site Number 348210	Budapest
Hungary	Investigational Site Number 348212	Budapest
Hungary	Investigational Site Number 348202	Urhida
Japan	Investigational Site Number 392214	Fujimi
Japan	Investigational Site Number 392215	Fujimi
Japan	Investigational Site Number 392206	Ise-Shi
Japan	Investigational Site Number 392217	Kitaazumi-Gun
Japan	Investigational Site Number 392210	Matsumoto-Shi
Japan	Investigational Site Number 392208	Matumoto
Japan	Investigational Site Number 392205	Midori-Shi
Japan	Investigational Site Number 392203	Mito-Shi
Japan	Investigational Site Number 392216	Sakai
Japan	Investigational Site Number 392213	Shimotsuke
Japan	Investigational Site Number 392218	Shunan-Shi
Japan	Investigational Site Number 392204	Yamagata-Shi
Latvia	Investigational Site Number 428203	Riga
Latvia	Investigational Site Number 428205	Riga
Latvia	Investigational Site Number 428206	Riga
Latvia	Investigational Site Number 428202	Sigulda
Latvia	Investigational Site Number 428201	Ventspils
Lithuania	Investigational Site Number 440203	Kaunas
Lithuania	Investigational Site Number 440204	Kaunas
Lithuania	Investigational Site Number 440201	Klaipeda
Lithuania	Investigational Site Number 440202	Klaipeda
Lithuania	Investigational Site Number 440205	Vilnius
Netherlands	Investigational Site Number 528204	Almere
Netherlands	Investigational Site Number 528209	Beek
Netherlands	Investigational Site Number 528205	Breda
Netherlands	Investigational Site Number 528207	Leiderdorp
Netherlands	Investigational Site Number 528203	Rotterdam
Netherlands	Investigational Site Number 528202	Velp
Puerto Rico	Investigational Site Number 840709	Cagua
Puerto Rico	Investigational Site Number 840706	Carolina
Puerto Rico	Investigational Site Number 840703	San Juan
Puerto Rico	Investigational Site Number 840704	San Juan
Puerto Rico	Investigational Site Number 840708	San Juan
Puerto Rico	Investigational Site Number 840710	San Juan
Romania	Investigational Site Number 642208	Bacau
Romania	Investigational Site Number 642201	Bucuresti
Romania	Investigational Site Number 642212	Bucuresti
Romania	Investigational Site Number 642202	Cluj-Napoca
Romania	Investigational Site Number 642213	Oradea
Romania	Investigational Site Number 642207	Resita
Romania	Investigational Site Number 642205	Sibiu
Romania	Investigational Site Number 642203	Targu Mures
Romania	Investigational Site Number 642204	Targu Mures
Romania	Investigational Site Number 642206	Timisoara
Romania	Investigational Site Number 642209	Timisoara
Slovakia	Investigational Site Number 703205	Banska Bystrica
Slovakia	Investigational Site Number 703202	Bardejov
Slovakia	Investigational Site Number 703203	Bratislava
Slovakia	Investigational Site Number 703201	Levice
Slovakia	Investigational Site Number 703206	Levice
Slovakia	Investigational Site Number 703207	Lucenec
Sweden	Investigational Site Number 752205	Kristianstad
Sweden	Investigational Site Number 752206	Malmö
Sweden	Investigational Site Number 752201	Stockholm
Sweden	Investigational Site Number 752204	Vällingby
United States	Investigational Site Number 840269	Albuquerque	New Mexico
United States	Investigational Site Number 840247	Asheville	North Carolina
United States	Investigational Site Number 840245	Atlanta	Georgia
United States	Investigational Site Number 840314	Avon	Indiana
United States	Investigational Site Number 840317	Avon	Indiana
United States	Investigational Site Number 840208	Baltimore	Maryland
United States	Investigational Site Number 840347	Bell Gardens	California
United States	Investigational Site Number 840219	Bend	Oregon
United States	Investigational Site Number 840299	Boca Raton	Florida
United States	Investigational Site Number 840285	Boynton Beach	Florida
United States	Investigational Site Number 840221	Bradenton	Florida
United States	Investigational Site Number 840260	Bristol	Tennessee
United States	Investigational Site Number 840239	Burke	Virginia
United States	Investigational Site Number 840273	Chandler	Arizona
United States	Investigational Site Number 840262	Chattanooga	Tennessee
United States	Investigational Site Number 840278	Chicago	Illinois
United States	Investigational Site Number 840320	Chicago	Illinois
United States	Investigational Site Number 840233	Clearwater	Florida
United States	Investigational Site Number 840330	Cleveland	Ohio
United States	Investigational Site Number 840249	Colorado Springs	Colorado
United States	Investigational Site Number 840307	Columbus	Ohio
United States	Investigational Site Number 840212	Coral Gables	Florida
United States	Investigational Site Number 840266	Coral Gables	Florida
United States	Investigational Site Number 840342	Corpus Christi	Texas
United States	Investigational Site Number 840294	Dakota Dunes	South Dakota
United States	Investigational Site Number 840242	Dallas	Texas
United States	Investigational Site Number 840268	Dallas	Texas
United States	Investigational Site Number 840292	Dallas	Texas
United States	Investigational Site Number 840315	Dallas	Texas
United States	Investigational Site Number 840331	Denver	Colorado
United States	Investigational Site Number 840214	Des Moines	Iowa
United States	Investigational Site Number 840326	Edinburg	Texas
United States	Investigational Site Number 840244	Escondido	California
United States	Investigational Site Number 840289	Fall River	Massachusetts
United States	Investigational Site Number 840257	Fresno	California
United States	Investigational Site Number 840213	Greenbrae	California
United States	Investigational Site Number 840296	Greensboro	North Carolina
United States	Investigational Site Number 840252	Greer	South Carolina
United States	Investigational Site Number 840306	Hamilton	New Jersey
United States	Investigational Site Number 840253	Haverhill	Massachusetts
United States	Investigational Site Number 840204	Hialeah	Florida
United States	Investigational Site Number 840248	Hollywood	Florida
United States	Investigational Site Number 840236	Honolulu	Hawaii
United States	Investigational Site Number 840218	Houston	Texas
United States	Investigational Site Number 840259	Houston	Texas
United States	Investigational Site Number 840328	Houston	Texas
United States	Investigational Site Number 840338	Houston	Texas
United States	Investigational Site Number 840267	Huntington Beach	California
United States	Investigational Site Number 840283	Idaho Falls	Idaho
United States	Investigational Site Number 840224	Jacksonville	Florida
United States	Investigational Site Number 840226	Jacksonville	Florida
United States	Investigational Site Number 840318	Jacksonville	Florida
United States	Investigational Site Number 840230	La Jolla	California
United States	Investigational Site Number 840235	La Mesa	California
United States	Investigational Site Number 840274	La Mesa	California
United States	Investigational Site Number 840201	Las Vegas	Nevada
United States	Investigational Site Number 840256	Las Vegas	Nevada
United States	Investigational Site Number 840349	Las Vegas	Nevada
United States	Investigational Site Number 840344	Lexington	Kentucky
United States	Investigational Site Number 840304	Little Rock	Arkansas
United States	Investigational Site Number 840222	Long Beach	California
United States	Investigational Site Number 840270	Madison Heights	Michigan
United States	Investigational Site Number 840206	Manassas	Virginia
United States	Investigational Site Number 840217	Mesa	Arizona
United States	Investigational Site Number 840348	Metairie	Louisiana
United States	Investigational Site Number 840228	Miami	Florida
United States	Investigational Site Number 840238	Miami	Florida
United States	Investigational Site Number 840302	Miami	Florida
United States	Investigational Site Number 840337	Miami Beach	Florida
United States	Investigational Site Number 840311	Milwaukee	Wisconsin
United States	Investigational Site Number 840324	Montgomery	Alabama
United States	Investigational Site Number 840275	Morganton	North Carolina
United States	Investigational Site Number 840202	Murray	Utah
United States	Investigational Site Number 840231	Murray	Kentucky
United States	Investigational Site Number 840310	New Hyde Park	New York
United States	Investigational Site Number 840290	New Orleans	Louisiana
United States	Investigational Site Number 840227	New Port Richey	Florida
United States	Investigational Site Number 840229	Norman	Oklahoma
United States	Investigational Site Number 840303	North Miami Beach	Florida
United States	Investigational Site Number 840225	Ocala	Florida
United States	Investigational Site Number 840210	Omaha	Nebraska
United States	Investigational Site Number 840263	Omaha	Nebraska
United States	Investigational Site Number 840300	Omaha	Nebraska
United States	Investigational Site Number 840291	Orlando	Florida
United States	Investigational Site Number 840316	Orlando	Florida
United States	Investigational Site Number 840232	Overland Park	Kansas
United States	Investigational Site Number 840216	Oviedo	Florida
United States	Investigational Site Number 840332	Palm Harbor	Florida
United States	Investigational Site Number 840243	Palm Springs	California
United States	Investigational Site Number 840327	Pearland	Texas
United States	Investigational Site Number 840288	Pembroke Pines	Florida
United States	Investigational Site Number 840220	Peoria	Arizona
United States	Investigational Site Number 840240	Philadelphia	Pennsylvania
United States	Investigational Site Number 840207	Phoenix	Arizona
United States	Investigational Site Number 840211	Phoenix	Arizona
United States	Investigational Site Number 840325	Port Charlotte	Florida
United States	Investigational Site Number 840246	Renton	Washington
United States	Investigational Site Number 840301	Rockville	Maryland
United States	Investigational Site Number 840343	Salt Lake City	Utah
United States	Investigational Site Number 840282	San Antonio	Texas
United States	Investigational Site Number 840203	Sea Girt	New Jersey
United States	Investigational Site Number 840295	Sicklerville	New Jersey
United States	Investigational Site Number 840237	Spartanburg	South Carolina
United States	Investigational Site Number 840250	Spring Valley	California
United States	Investigational Site Number 840276	Springfield	Illinois
United States	Investigational Site Number 840309	St. Petersburg	Florida
United States	Investigational Site Number 840323	Stockbridge	Georgia
United States	Investigational Site Number 840251	Tampa	Florida
United States	Investigational Site Number 840209	Temecula	California
United States	Investigational Site Number 840234	Tempe	Arizona
United States	Investigational Site Number 840264	Tempe	Arizona
United States	Investigational Site Number 840308	Tipton	Pennsylvania
United States	Investigational Site Number 840287	Topeka	Kansas
United States	Investigational Site Number 840297	Torrance	California
United States	Investigational Site Number 840272	Tustin	California
United States	Investigational Site Number 840223	Walnut Creek	California
United States	Investigational Site Number 840339	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czech Republic,  Denmark,  Estonia,  Finland,  Hungary,  Japan,  Latvia,  Lithuania,  Netherlands,  Puerto Rico,  Romania,  Slovakia,  Sweden, 

References & Publications (1)

Bolli GB, Riddle MC, Bergenstal RM, Ziemen M, Sestakauskas K, Goyeau H, Home PD; on behalf of the EDITION 3 study investigators. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-low — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Baseline to Month 6 Endpoint	Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.	Baseline, Month 6	No
Secondary	Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6	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]). Only nocturnal hypoglycemia occurring before initiation of rescue therapy were considered in the analysis. Week 9 and Month 6 value correspond to the observed value at Week 9 and Month 6 visit respectively.	Week 9 Up to Month 6	No
Secondary	Change in 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. Except for baseline value average of preinjection SMPG was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.	Baseline, Month 6	No
Secondary	Variability of Preinjection SMPG at 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. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.	Month 6	No
Secondary	Percentage of Participants With HbA1c <7% at Month 6	Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.	Month 6	No
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint	Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.	Baseline, Month 6	No
Secondary	Percentage of Participants With FPG <5.6 mmol/L (100 mg/dL) at Month 6	Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.	Month 6	No
Secondary	Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6	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 8-point SMPG profiles measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.	Baseline, Month 6	No
Secondary	Change in 24-hour Average 8-point SMPG Profile From Baseline to Month 6 Endpoint	Change in 24-hour average of 8-point SMPG profile. 8-point SMPG was assessed at: 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 24-hour average 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.	Baseline, Month 6	No
Secondary	Change in Variability of 24 Hour Average 8-point SMPG Profiles From Baseline to Month 6 Endpoint	Variability is assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 5 measurements of the 8-point profiles. Only variability of 24-hour 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.	Baseline, Month 6	No
Secondary	Change in Daily Basal Insulin Dose From Baseline to Month 6	Only insulin dose measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.	Baseline, Month 6	No
Secondary	Change in Total 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 DTSQ total score measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.	Baseline, Month 6	No
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 12 months	Yes