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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01499095
First received: December 16, 2011
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

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

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Lantus (Insulin glargine)
Drug: HOE901-U300 (new formulation of 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: 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

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 ]
    Only measurements performed before initiation of rescue therapy were considered in the analysis.


Secondary Outcome Measures:
  • Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint [ Time Frame: Week 9 Up to Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

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

  • Percentage of Participants With HbA1c <7% at Month 6 Endpoint [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Only measurements performed before initiation of rescue therapy were considered in the analysis.

  • Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    Only measurements performed before initiation of rescue therapy were considered in the analysis.

  • Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Only measurements performed before initiation of rescue therapy were considered in the analysis.

  • 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. Only measurements performed before initiation of rescue therapy were considered in the analysis.

  • Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    Only measurements performed before initiation of rescue therapy were considered in the analysis.

  • Change in 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. Only measurements performed before initiation of rescue therapy were considered in the analysis.

  • 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).


Other Outcome Measures:
  • Change in HbA1c From Month 6 to Month 9 [ Time Frame: Month 6 up to Month 9 ] [ Designated as safety issue: No ]
    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.


Enrollment: 811
Study Start Date: December 2011
Study Completion Date: November 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HOE901-U300 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 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.
Active Comparator: Lantus 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).
Other Name: Lantus

Detailed 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
  Eligibility

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

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.

  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: NCT01499095

  Show 213 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01499095     History of Changes
Other Study ID Numbers: EFC11629, 2010-023770-39, U1111-1118-6943
Study First Received: December 16, 2011
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 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Hypoglycemic Agents
Insulin
Insulin, Globin Zinc
Insulin, Long-Acting
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 30, 2015