Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 1 Diabetes Mellitus (EDITION IV)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01683266
First received: September 7, 2012
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

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

Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: HOE901-U300 (Insulin glargine new formulation)
Drug: Lantus (Insulin glargine)
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change In HbA1c From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants With HbA1c <7% at Month 6 Endpoint [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HbA1c Less Than or Equal to 6.5% at Month 6 Endpoint [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Change In Average Pre-Injection Self-Monitored Plasma Glucose (SMPG) From Baseline Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in Variability of Pre-injection SMPG From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in Fasting Plasma Glucose From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Fasting Plasma Glucose (FPG) <5.6 mmol/L (100 mg/dL) At Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants With FPG <7.2 mmol/L (130 mg/dL) at Month 6 Endpoint [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in Daily Average Total Insulin Dose From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
  • Change in Total Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 [ Time Frame: Up to Month 12 ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 549
Study Start Date: September 2012
Study Completion Date: March 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HOE901-U300
HOE901-U300 (new insulin glargine 300 units per milliliter [U/mL]) subcutaneous (SC) injection once daily in morning or 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]).
Drug: HOE901-U300 (Insulin glargine new formulation)
Active Comparator: Lantus
Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily in morning or 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).
Drug: Lantus (Insulin glargine)

Detailed 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01683266

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Locations
United States, Arizona
Investigational Site Number 840156
Chandler, Arizona, United States, 85224
United States, Arkansas
Investigational Site Number 840177
Little Rock, Arkansas, United States, 72205
United States, California
Investigational Site Number 840430
Bell Gardens, California, United States, 90201
Investigational Site Number 840131
Escondido, California, United States, 92025
Investigational Site Number 840140
Fresno, California, United States, 93720
Investigational Site Number 840107
Greenbrae, California, United States, 94904
Investigational Site Number 840149
Huntington Beach, California, United States, 92648
Investigational Site Number 840120
La Jolla, California, United States, 92037
Investigational Site Number 840123
La Jolla, California, United States, 92037
Investigational Site Number 840159
La Mesa, California, United States, 91942
Investigational Site Number 840114
Long Beach, California, United States, 90806
Investigational Site Number 840189
Mission Hills, California, United States, 91345
Investigational Site Number 840105
Temecula, California, United States, 92591
Investigational Site Number 840155
Tustin, California, United States, 92780
Investigational Site Number 840115
Walnut Creek, California, United States, 94598
United States, Colorado
Investigational Site Number 840188
Denver, Colorado, United States, 80262
Investigational Site Number 840160
Denver, Colorado, United States, 80239
Investigational Site Number 840143
Longmont, Colorado, United States, 80501
United States, Connecticut
Investigational Site Number 840196
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Investigational Site Number 840104
Washington, District of Columbia, United States, 20003
United States, Florida
Investigational Site Number 840152
Boca Raton, Florida, United States, 33432
Investigational Site Number 840113
Bradenton, Florida, United States, 34208
Investigational Site Number 840102
Hialeah, Florida, United States, 33012
Investigational Site Number 840134
Hollywood, Florida, United States, 33021
Investigational Site Number 840185
Jacksonville, Florida, United States, 32216
Investigational Site Number 840116
Jacksonville, Florida, United States, 32258
Investigational Site Number 840118
Miami, Florida, United States, 33144
Investigational Site Number 840126
Miami, Florida, United States, 33144
Investigational Site Number 840138
Miami, Florida, United States, 33136
Investigational Site Number 840179
Miami, Florida, United States, 33176
Investigational Site Number 840117
New Port Richey, Florida, United States, 34652
Investigational Site Number 840183
North Miami Beach, Florida, United States, 33162
Investigational Site Number 840174
Orlando, Florida, United States, 32806
Investigational Site Number 840110
Oviedo, Florida, United States, 32765
Investigational Site Number 840178
Palm Harbor, Florida, United States, 34684
Investigational Site Number 840181
Tampa, Florida, United States, 33613
Investigational Site Number 840420
West Palm Beach, Florida, United States, 33401
United States, Georgia
Investigational Site Number 840195
Atlanta, Georgia, United States, 30318
United States, Hawaii
Investigational Site Number 840124
Honolulu, Hawaii, United States, 96814
United States, Idaho
Investigational Site Number 840167
Idaho Falls, Idaho, United States, 83404
Investigational Site Number 840163
Nampa, Idaho, United States, 83686
United States, Illinois
Investigational Site Number 840162
Springfield, Illinois, United States, 62704
United States, Indiana
Investigational Site Number 840172
Avon, Indiana, United States, 46123
Investigational Site Number 840197
Indianapolis, Indiana, United States, 46202
United States, Iowa
Investigational Site Number 840108
Des Moines, Iowa, United States, 50314
Investigational Site Number 840407
Iowa City, Iowa, United States, 52242
United States, Kansas
Investigational Site Number 840170
Topeka, Kansas, United States, 66614
Investigational Site Number 840129
Wichita, Kansas, United States, 67211
United States, Kentucky
Investigational Site Number 840421
Lexington, Kentucky, United States, 40503
United States, Louisiana
Investigational Site Number 840426
Metairie, Louisiana, United States, 70006
Investigational Site Number 840164
New Orleans, Louisiana, United States, 70112
United States, Maryland
Investigational Site Number 840180
Rockville, Maryland, United States, 20852
United States, Massachusetts
Investigational Site Number 840409
Boston, Massachusetts, United States, 02215
Investigational Site Number 840137
Haverhill, Massachusetts, United States, 1830
United States, Michigan
Investigational Site Number 840408
Detroit, Michigan, United States, 48202
Investigational Site Number 840153
Madison Heights, Michigan, United States, 48071
United States, Minnesota
Investigational Site Number 840171
St Louis Park, Minnesota, United States, 55416
United States, Missouri
Investigational Site Number 840184
St Louis, Missouri, United States, 63110
United States, Montana
Investigational Site Number 840406
Billings, Montana, United States, 59102
United States, Nebraska
Investigational Site Number 840106
Omaha, Nebraska, United States, 68131
Investigational Site Number 840145
Omaha, Nebraska, United States, 68131
United States, Nevada
Investigational Site Number 840139
Las Vegas, Nevada, United States, 89148
United States, New Mexico
Investigational Site Number 840151
Albuquerque, New Mexico, United States, 87106
United States, New York
Investigational Site Number 840191
New Hyde Park, New York, United States, 11042
Investigational Site Number 840173
Syracuse, New York, United States, 13210
United States, North Carolina
Investigational Site Number 840133
Asheville, North Carolina, United States, 28803
Investigational Site Number 840175
Chapel Hill, North Carolina, United States, 27599-7295
Investigational Site Number 840142
Greensboro, North Carolina, United States, 27408
Investigational Site Number 840154
Mooresville, North Carolina, United States, 28117
Investigational Site Number 840161
Morganton, North Carolina, United States, 28655
United States, Ohio
Investigational Site Number 840169
Mentor, Ohio, United States, 44060
United States, Oklahoma
Investigational Site Number 840119
Norman, Oklahoma, United States, 73069
United States, Oregon
Investigational Site Number 840112
Bend, Oregon, United States, 97701
United States, Pennsylvania
Investigational Site Number 840128
Philadelphia, Pennsylvania, United States, 19139
United States, South Carolina
Investigational Site Number 840136
Greer, South Carolina, United States, 29651
United States, South Dakota
Investigational Site Number 840122
Dakota Dunes, South Dakota, United States, 57049
United States, Tennessee
Investigational Site Number 840144
Chattanooga, Tennessee, United States, 37404
Investigational Site Number 840187
Nashville, Tennessee, United States, 37232
United States, Texas
Investigational Site Number 840157
Austin, Texas, United States, 78731
Investigational Site Number 840109
Austin, Texas, United States, 78731
Investigational Site Number 840150
Dallas, Texas, United States, 75230
Investigational Site Number 840412
Dallas, Texas, United States, 75231
Investigational Site Number 840130
Houston, Texas, United States, 77030
Investigational Site Number 840141
Houston, Texas, United States, 77095
Investigational Site Number 840166
San Antonio, Texas, United States, 78229
United States, Utah
Investigational Site Number 840101
Murray, Utah, United States, 84123
United States, Virginia
Investigational Site Number 840125
Burke, Virginia, United States, 22015
Investigational Site Number 840427
Chesapeake, Virginia, United States, 23321
Investigational Site Number 840103
Manassas, Virginia, United States, 20110
United States, Washington
Investigational Site Number 840132
Renton, Washington, United States, 98055
Investigational Site Number 840403
Seattle, Washington, United States, 98195
Investigational Site Number 840402
Spokane, Washington, United States, 99220
Investigational Site Number 840127
Tacoma, Washington, United States, 98415-0299
United States, Wisconsin
Investigational Site Number 840411
Milwaukee, Wisconsin, United States, 53209
Canada
Investigational Site Number 124110
Coquitlam, Canada, V3K 3P4
Investigational Site Number 124104
Laval, Canada, H7T 2P5
Investigational Site Number 124108
Mirabel, Canada, J7J 2K8
Investigational Site Number 124109
Montreal, Canada, H1Y 3L1
Investigational Site Number 124105
Thornhill, Canada, L4J 8L7
Investigational Site Number 124101
Toronto, Canada, M4R 2G4
Czech Republic
Investigational Site Number 203102
Brno, Czech Republic, 62500
Investigational Site Number 203104
Praha 10, Czech Republic, 10034
Investigational Site Number 203103
Praha 8, Czech Republic, 18100
Denmark
Investigational Site Number 208103
Esbjerg, Denmark, 6700
Investigational Site Number 208105
Gentofte, Denmark, 2900
Investigational Site Number 208104
København Nv, Denmark, 2400
Investigational Site Number 208107
Køge, Denmark, 4600
Investigational Site Number 208102
Ålborg, Denmark, 9100
Estonia
Investigational Site Number 233104
Pärnu, Estonia, 80018
Investigational Site Number 233105
Tallinn, Estonia, 13419
Investigational Site Number 233101
Tartu, Estonia, 50410
Investigational Site Number 233106
Tartu, Estonia, 50406
Investigational Site Number 233103
Viljandimaa, Estonia, 71024
Finland
Investigational Site Number 246102
Kokkola, Finland, 67100
Investigational Site Number 246101
Kuopio, Finland, 70210
Investigational Site Number 246106
Loimaa, Finland, 32200
Investigational Site Number 246105
Oulu, Finland, 90100
Investigational Site Number 246103
Tampere, Finland, 33100
Hungary
Investigational Site Number 348103
Budapest, Hungary, 1036
Investigational Site Number 348107
Budapest, Hungary, 1088
Investigational Site Number 348108
Budapest, Hungary, 1083
Investigational Site Number 348106
Debrecen, Hungary, 4043
Investigational Site Number 348102
Gyula, Hungary, 5700
Investigational Site Number 348101
Urhida, Hungary, 8142
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, Japan
Latvia
Investigational Site Number 428106
Limbazi, Latvia, LV-4001
Investigational Site Number 428103
Riga, Latvia, LV-1002
Investigational Site Number 428105
Riga, Latvia, LV-1050
Investigational Site Number 428102
Sigulda, Latvia, LV-2150
Investigational Site Number 428101
Ventspils, Latvia, LV-3601
Netherlands
Investigational Site Number 528101
Almere, Netherlands, 1311 RL
Investigational Site Number 528103
Beek, Netherlands, 6191 JW
Investigational Site Number 528105
Nijmegen, Netherlands, 6525 GA
Investigational Site Number 528104
Venlo, Netherlands, 5912 BL
Investigational Site Number 528102
Zwijndrecht, Netherlands, 3331 LZ
Puerto Rico
Investigational Site Number 840601
Ponce, Puerto Rico, 07716
Investigational Site Number 840602
Ponce, Puerto Rico, 00717
Romania
Investigational Site Number 642107
Bacau, Romania, 600164
Investigational Site Number 642103
Brasov, Romania, 500365
Investigational Site Number 642109
Oradea, Romania, 410169
Investigational Site Number 642106
Resita, Romania, 320076
Investigational Site Number 642104
Sibiu, Romania, 550371
Investigational Site Number 642101
Targu Mures, Romania, 540142
Investigational Site Number 642102
Targu Mures, Romania, 540142
Investigational Site Number 642105
Timisoara, Romania, 300133
Investigational Site Number 642108
Timisoara, Romania, 300456
Sweden
Investigational Site Number 752103
Goteborg, Sweden, 41345
Investigational Site Number 752105
Kristianstad, Sweden, 29185
Investigational Site Number 752101
Stockholm, Sweden, 11522
Investigational Site Number 752104
Vällingby, Sweden, 16268
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01683266     History of Changes
Other Study ID Numbers: EFC12456, 2012-001524-35, U1111-1128-5517
Study First Received: September 7, 2012
Results First Received: March 24, 2015
Last Updated: April 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Glargine
Insulin
Insulin, Globin Zinc
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2015