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: May 28, 2015
Last verified: May 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

  Show 147 Study Locations
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: May 28, 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 September 01, 2015