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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01676220
First received: August 28, 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 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


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

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 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.


Secondary Outcome Measures:
  • Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 [ 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 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.

  • Change in Preinjection Self-Monitored Plasma Glucose (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. 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.

  • Variability of Preinjection SMPG at Month 6 Endpoint [ Time Frame: 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. 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.

  • Percentage of Participants With HbA1c <7% at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With FPG <5.6 mmol/L (100 mg/dL) at Month 6 [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 [ 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 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.

  • Change in 24-hour Average 8-point SMPG Profile From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in Variability of 24 Hour Average 8-point SMPG Profiles From Baseline to Month 6 Endpoint [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change in Daily Basal Insulin Dose From Baseline to Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • 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. 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.

  • Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 [ Time Frame: Up to 12 months ] [ 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: 878
Study Start Date: August 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 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]).
Active Comparator: Lantus Drug: 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).
Other Name: Lantus

Detailed 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
  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 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.

  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: NCT01676220

  Show 224 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01676220     History of Changes
Other Study ID Numbers: EFC12347, 2012-000146-35, U1111-1124-5261
Study First Received: August 28, 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 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 April 23, 2015