Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus Clinical Trial

— EDITION IV  

Official title:

A 6-Month, Multicenter, Randomized, Open-label, Parallel-group Study Comparing the Efficacy and Safety of a New Formulation of Insulin Glargine and Lantus® Injected in the Morning or Evening in Patients With Type 1 Diabetes Mellitus With a 6-month Safety Extension Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01683266
• Other study ID #: EFC12456
• Secondary ID: 2012-001524-35U1
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2012
• Last updated: May 28, 2015
• Start date: September 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 (overall, regardless the injection time) in terms of change of HbA1c from baseline to endpoint (scheduled Month 6) in participants with type 1 diabetes mellitus

Secondary Objective:

• To compare HOE901-U300 and Lantus when given in the morning or in the evening in terms of:

• Change of HbA1c from baseline to endpoint (scheduled Month 6)

• Change from baseline to endpoint (Month 6) in fasting plasma glucose (FPG), plasma glucose prior to injection of study drug, plasma glucose at 03:00 hours, mean plasma glucose (8-point profiles), glucose variability, treatment satisfaction and health related quality of life in participants with Type 1 Diabetes Mellitus (T1DM)

• Reaching target HbA1c values and controlled plasma glucose (all and reaching target without hypoglycemia)

• Frequency of occurrence and diurnal distribution of hypoglycemia by category of hypoglycemia (symptomatic, asymptomatic, nocturnal, severe, probable and relative)

• Safety and tolerability of HOE901-U300 including development of anti-insulin antibody (AIAs) during the 12-month study period

Description:

The maximum study duration was up to approximately 54 weeks per participants:

• Up to 2-week screening period

• 6-month open-label comparative efficacy and safety treatment period

• 6-month open-label comparative safety extension period

• 48-hour post-treatment safety follow-up period

Recruitment information / eligibility

• Status: Completed
• Enrollment: 549
• 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 1 diabetes mellitus

Exclusion criteria:

• HbA1c less than (<) 7.0% (53 mmol/mol) or greater than (>) 10% (86 mmol/mol) at screening

• Less than 1 year on any basal plus mealtime insulin and self-monitoring of blood glucose before screening visit

• Participants not on stable insulin dose (+/-20 percent total basal insulin dose) in the last 30 days prior to screening visit

• Participants using pre-mix insulins, human regular insulin as mealtime insulin and/or any glucose-lowering drugs other than basal insulin and mealtime analogue insulin in the last 3 months before screening visit

• Use of an insulin pump in the last 6 months before screening visit and no plan to switch to insulin pump in the next 12 months

• Not willing to inject insulin glargine as assigned by the randomization process once daily in the morning or evening;

• Severe hypoglycemia resulting in coma/seizures, and/or hospitalization for diabetic ketoacidosis in the last 6 months before screening visit

• Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (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 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• HOE901-U300 (Insulin glargine new formulation)

• Lantus (Insulin glargine)

Locations

Country	Name	City	State
Canada	Investigational Site Number 124110	Coquitlam
Canada	Investigational Site Number 124104	Laval
Canada	Investigational Site Number 124108	Mirabel
Canada	Investigational Site Number 124109	Montreal
Canada	Investigational Site Number 124105	Thornhill
Canada	Investigational Site Number 124101	Toronto
Czech Republic	Investigational Site Number 203102	Brno
Czech Republic	Investigational Site Number 203104	Praha 10
Czech Republic	Investigational Site Number 203103	Praha 8
Denmark	Investigational Site Number 208102	Ålborg
Denmark	Investigational Site Number 208103	Esbjerg
Denmark	Investigational Site Number 208105	Gentofte
Denmark	Investigational Site Number 208104	København Nv
Denmark	Investigational Site Number 208107	Køge
Estonia	Investigational Site Number 233104	Pärnu
Estonia	Investigational Site Number 233105	Tallinn
Estonia	Investigational Site Number 233101	Tartu
Estonia	Investigational Site Number 233106	Tartu
Estonia	Investigational Site Number 233103	Viljandimaa
Finland	Investigational Site Number 246102	Kokkola
Finland	Investigational Site Number 246101	Kuopio
Finland	Investigational Site Number 246106	Loimaa
Finland	Investigational Site Number 246105	Oulu
Finland	Investigational Site Number 246103	Tampere
Hungary	Investigational Site Number 348103	Budapest
Hungary	Investigational Site Number 348107	Budapest
Hungary	Investigational Site Number 348108	Budapest
Hungary	Investigational Site Number 348106	Debrecen
Hungary	Investigational Site Number 348102	Gyula
Hungary	Investigational Site Number 348101	Urhida
Japan	Investigational Site Number 392110	Aisai-Shi
Japan	Investigational Site Number 392105	Ise-Shi
Japan	Investigational Site Number 392104	Karatsu-Shi
Japan	Investigational Site Number 392111	Kitakyushu-Shi
Japan	Investigational Site Number 392112	Matsumoto-Shi
Japan	Investigational Site Number 392108	Matumoto
Japan	Investigational Site Number 392103	Midori-Shi
Japan	Investigational Site Number 392107	Mito-Shi
Japan	Investigational Site Number 392101	Sakai-Shi
Japan	Investigational Site Number 392102	Tomishiro
Japan	Investigational Site Number 392106	Yamagata-Shi
Latvia	Investigational Site Number 428106	Limbazi
Latvia	Investigational Site Number 428103	Riga
Latvia	Investigational Site Number 428105	Riga
Latvia	Investigational Site Number 428102	Sigulda
Latvia	Investigational Site Number 428101	Ventspils
Netherlands	Investigational Site Number 528101	Almere
Netherlands	Investigational Site Number 528103	Beek
Netherlands	Investigational Site Number 528105	Nijmegen
Netherlands	Investigational Site Number 528104	Venlo
Netherlands	Investigational Site Number 528102	Zwijndrecht
Puerto Rico	Investigational Site Number 840602	Ponce
Romania	Investigational Site Number 642107	Bacau
Romania	Investigational Site Number 642103	Brasov
Romania	Investigational Site Number 642109	Oradea
Romania	Investigational Site Number 642106	Resita
Romania	Investigational Site Number 642104	Sibiu
Romania	Investigational Site Number 642101	Targu Mures
Romania	Investigational Site Number 642102	Targu Mures
Romania	Investigational Site Number 642105	Timisoara
Romania	Investigational Site Number 642108	Timisoara
Sweden	Investigational Site Number 752103	Goteborg
Sweden	Investigational Site Number 752105	Kristianstad
Sweden	Investigational Site Number 752101	Stockholm
Sweden	Investigational Site Number 752104	Vällingby
United States	Investigational Site Number 840151	Albuquerque	New Mexico
United States	Investigational Site Number 840133	Asheville	North Carolina
United States	Investigational Site Number 840195	Atlanta	Georgia
United States	Investigational Site Number 840109	Austin	Texas
United States	Investigational Site Number 840157	Austin	Texas
United States	Investigational Site Number 840172	Avon	Indiana
United States	Investigational Site Number 840104	Baltimore	Maryland
United States	Investigational Site Number 840430	Bell Gardens	California
United States	Investigational Site Number 840112	Bend	Oregon
United States	Investigational Site Number 840113	Bradenton	Florida
United States	Investigational Site Number 840125	Burke	Virginia
United States	Investigational Site Number 840156	Chandler	Arizona
United States	Investigational Site Number 840175	Chapel Hill	North Carolina
United States	Investigational Site Number 840144	Chattanooga	Tennessee
United States	Investigational Site Number 840427	Chesapeake	Virginia
United States	Investigational Site Number 840122	Dakota Dunes	South Dakota
United States	Investigational Site Number 840150	Dallas	Texas
United States	Investigational Site Number 840412	Dallas	Texas
United States	Investigational Site Number 840160	Denver	Colorado
United States	Investigational Site Number 840188	Denver	Colorado
United States	Investigational Site Number 840108	Des Moines	Iowa
United States	Investigational Site Number 840408	Detroit	Michigan
United States	Investigational Site Number 840131	Escondido	California
United States	Investigational Site Number 840140	Fresno	California
United States	Investigational Site Number 840107	Greenbrae	California
United States	Investigational Site Number 840136	Greer	South Carolina
United States	Investigational Site Number 840137	Haverhill	Massachusetts
United States	Investigational Site Number 840102	Hialeah	Florida
United States	Investigational Site Number 840134	Hollywood	Florida
United States	Investigational Site Number 840124	Honolulu	Hawaii
United States	Investigational Site Number 840130	Houston	Texas
United States	Investigational Site Number 840141	Houston	Texas
United States	Investigational Site Number 840149	Huntington Beach	California
United States	Investigational Site Number 840167	Idaho Falls	Idaho
United States	Investigational Site Number 840197	Indianapolis	Indiana
United States	Investigational Site Number 840407	Iowa City	Iowa
United States	Investigational Site Number 840116	Jacksonville	Florida
United States	Investigational Site Number 840185	Jacksonville	Florida
United States	Investigational Site Number 840120	La Jolla	California
United States	Investigational Site Number 840123	La Mesa	California
United States	Investigational Site Number 840159	La Mesa	California
United States	Investigational Site Number 840139	Las Vegas	Nevada
United States	Investigational Site Number 840421	Lexington	Kentucky
United States	Investigational Site Number 840177	Little Rock	Arkansas
United States	Investigational Site Number 840114	Long Beach	California
United States	Investigational Site Number 840153	Madison Heights	Michigan
United States	Investigational Site Number 840103	Manassas	Virginia
United States	Investigational Site Number 840169	Mentor	Ohio
United States	Investigational Site Number 840426	Metairie	Louisiana
United States	Investigational Site Number 840126	Miami	Florida
United States	Investigational Site Number 840179	Miami	Florida
United States	Investigational Site Number 840411	Milwaukee	Wisconsin
United States	Investigational Site Number 840189	Mission Hills	California
United States	Investigational Site Number 840161	Morganton	North Carolina
United States	Investigational Site Number 840101	Murray	Utah
United States	Investigational Site Number 840163	Nampa	Idaho
United States	Investigational Site Number 840187	Nashville	Tennessee
United States	Investigational Site Number 840196	New Haven	Connecticut
United States	Investigational Site Number 840191	New Hyde Park	New York
United States	Investigational Site Number 840117	New Port Richey	Florida
United States	Investigational Site Number 840119	Norman	Oklahoma
United States	Investigational Site Number 840106	Omaha	Nebraska
United States	Investigational Site Number 840145	Omaha	Nebraska
United States	Investigational Site Number 840174	Orlando	Florida
United States	Investigational Site Number 840110	Oviedo	Florida
United States	Investigational Site Number 840178	Palm Harbor	Florida
United States	Investigational Site Number 840132	Renton	Washington
United States	Investigational Site Number 840180	Rockville	Maryland
United States	Investigational Site Number 840166	San Antonio	Texas
United States	Investigational Site Number 840403	Seattle	Washington
United States	Investigational Site Number 840402	Spokane	Washington
United States	Investigational Site Number 840162	Springfield	Illinois
United States	Investigational Site Number 840184	St Louis	Missouri
United States	Investigational Site Number 840171	St Louis Park	Minnesota
United States	Investigational Site Number 840173	Syracuse	New York
United States	Investigational Site Number 840127	Tacoma	Washington
United States	Investigational Site Number 840181	Tampa	Florida
United States	Investigational Site Number 840105	Temecula	California
United States	Investigational Site Number 840170	Topeka	Kansas
United States	Investigational Site Number 840155	Tustin	California
United States	Investigational Site Number 840115	Walnut Creek	California
United States	Investigational Site Number 840420	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change In HbA1c From Baseline to Month 6 Endpoint		Baseline, Month 6	No
Secondary	Percentage of Participants With HbA1c <7% at Month 6 Endpoint		Month 6	No
Secondary	Percentage of Participants With HbA1c Less Than or Equal to 6.5% at Month 6 Endpoint		Month 6	No
Secondary	Change In Average Pre-Injection Self-Monitored Plasma Glucose (SMPG) From Baseline 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	No
Secondary	Change in Variability of Pre-injection 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	No
Secondary	Change in Fasting Plasma Glucose From Baseline to Month 6 Endpoint		Baseline, Month 6	No
Secondary	Percentage of Participants With Fasting Plasma Glucose (FPG) <5.6 mmol/L (100 mg/dL) At Month 6		Month 6	No
Secondary	Percentage of Participants With FPG <7.2 mmol/L (130 mg/dL) at Month 6 Endpoint		Month 6	No
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	No
Secondary	Change in Daily Average Total Insulin Dose From Baseline to Month 6 Endpoint		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.	Baseline, Month 6	No
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	Yes