Insulin Glargine Injection Treatment in Place of Thiazolidinedione (TZD), Sulfonylurea, or Metformin in Triple Agent Therapy for Type 2 Diabetes Mellitus (T2DM) Adult Subjects With Unsatisfactory Control

This study has been terminated.
(Due to technical issues relating to the Electronic diary data.)
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00283049
First received: January 26, 2006
Last updated: January 7, 2011
Last verified: January 2011
  Purpose

The purpose of this study is to compare the change in hemoglobin A1c (HbA1c) from baseline to Week 12 between the 3 treatment arms.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Insulin Glargine
Drug: Insulin Glulisine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Insulin Glargine Injection [rDNA Origin] Treatment in Place of the TZD or the Sulfonylurea or Metformin in Triple Agent Therapy for T2DM Adult Subjects With Unsatisfactory Control

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12 [ Time Frame: 12 weeks from Baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline to Individual Time Points in HbA1c, Insulin Doses, and Total Insulin Dosage [ Time Frame: 60 weeks from Baseline ] [ Designated as safety issue: No ]
  • Percentage of Subjects Achieving an HbA1C Less Than (<) 7.0% and Less Than (<) 6.5% [ Time Frame: 60 weeks from Baseline ] [ Designated as safety issue: No ]
  • Change From Baseline to Study Time Points in 7-point Blood Glucose (BG) Profile (Before Meals, 2 Hours After Meals, at Bedtime) [ Time Frame: 60 weeks from Baseline ] [ Designated as safety issue: No ]
  • Change From Baseline to End of Study and to Individual Time Points in Components of Lipid Profile (Total Cholesterol, High-density Lipoprotein Cholesterol [HDL], Low-density Lipoprotein Cholesterol [LDL], Triglycerides, LDL Subfractions) [ Time Frame: 60 weeks from Baseline ] [ Designated as safety issue: No ]
  • Occurrences of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia, and Serious Hypoglycemia [ Time Frame: 60 weeks from Baseline ] [ Designated as safety issue: Yes ]
    • Symptomatic hypoglycemia (BG<70 mg/dL, BG<50 mg/dL): including 1 or more symptoms: headache, dizziness, general feeling of weakness, drowsiness, confusion, pallor, irritability, trembling, sweating, rapid heartbeat & a cold, clammy feeling.
    • Mild-to-moderate hypoglycemia: SMBG ≥ 36 mg/dL but <70 mg/dL
    • Severe hypoglycemia: assistance of another party is required & either:

      • SMBG of <36 mg/dL, or
      • with prompt response to treatment with oral carbohydrates, IV glucose or glucagon.
    • Serious hypoglycemia:

      • Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion.

  • Rate of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia and Serious Hypoglycemia [ Time Frame: 60 Weeks from Baseline ] [ Designated as safety issue: Yes ]
    • Symptomatic hypoglycemia (BG<70 mg/dL, BG<50 mg/dL): including 1 or more symptoms: headache, dizziness, general feeling of weakness, drowsiness, confusion, pallor, irritability, trembling, sweating, rapid heartbeat & a cold, clammy feeling.
    • Mild-to-moderate hypoglycemia: SMBG ≥ 36 mg/dL but <70 mg/dL
    • Severe hypoglycemia: assistance of another party is required & either:

      • SMBG of <36 mg/dL, or
      • with prompt response to treatment with oral carbohydrates, IV glucose or glucagon.
    • Serious hypoglycemia:

      • Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion.


Enrollment: 390
Study Start Date: February 2006
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulins + Sulfonylurea (SU) + Thiazolidinedione (TZD)
Arm 1: Insulin glargine administered subcutaneously once daily plus a sulfonylurea and a TZD. Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)
Drug: Insulin Glargine
Insulin glargine administered subcutaneously once daily.
Drug: Insulin Glulisine
Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)
Experimental: Insulins + Metformin (MET) + Thiazolidinedione (TZD)
Arm 2: Insulin glargine administered subcutaneously once daily plus metformin and a TZD. Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)
Drug: Insulin Glargine
Insulin glargine administered subcutaneously once daily.
Drug: Insulin Glulisine
Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)
Experimental: Insulins + Metformin (MET) + Sulfonylurea (SU)
Arm 3: Insulin glargine administered subcutaneously once daily plus metformin and a sulfonylurea. Insulin glulisine will be added arms after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)
Drug: Insulin Glargine
Insulin glargine administered subcutaneously once daily.
Drug: Insulin Glulisine
Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects meeting all of the following criteria will be considered for enrollment into the study:

  1. 18 to 79 years of age, inclusive
  2. Diagnosis of type 2 diabetes mellitus
  3. Continuous treatment with therapeutic dosages of a thiazolidinedione (rosiglitazone or pioglitazone), metformin, and a sulfonylurea daily prior to entering the study
  4. Screening HbA1c ≥ 7.0%
  5. Fasting C-peptide concentration ≥ 0.27 ng/ml
  6. Negative glutamic acid decarboxylase (GAD) antibodies
  7. Demonstrated ability and willingness to perform self-monitoring blood glucose (SMBG) using a plasma-referenced glucose meter and to maintain an electronic diary
  8. Demonstrated ability and willingness to use an electronic diary to record SMBG results, insulin doses, and hypoglycemic events.
  9. Signed, informed consent and Health Insurance Portability and Accountability Act (HIPAA) documentation

Exclusion Criteria:

  1. Stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris, within the last 12 months
  2. Cardiac status New York Heart Association (NYHA) III-IV
  3. Impaired renal function as shown by, but not limited to, serum creatinine ≥ 1.5 mg/dL for males, or ≥ 1.4 mg/dL for females
  4. Chronic use of insulin: (more than 3 weeks of continuous use) in the past 12 months
  5. Acute infection
  6. Clinically significant peripheral edema
  7. Acute or chronic history of metabolic acidosis, including diabetic ketoacidosis
  8. Clinical evidence of active liver disease, or serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of the normal range
  9. History of hypoglycemia unawareness
  10. Pregnancy or lactation
  11. Known hypersensitivity to insulin glargine or any of the components of Lantus®
  12. Known hypersensitivity to insulin glulisine or any of the components of Apidra®
  13. Any malignancy within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or adequately treated cervical carcinoma in situ
  14. Current addiction or current alcohol abuse, or history of substance or alcohol abuse within the last 2 years
  15. Diagnosis of dementia
  16. Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
  17. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
  18. subject is currently taking or was treated with the following medications 3 months prior to screening: Byetta(exenatide), Starlix(nateglinide),Prandin (repaglinide), Januvia(sitagliptin), Janumet(metformin + sitagliptin)
  19. Any disease or condition that in the opinion of the investigator and/or sponsor may interfere with the completion of the study
  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: NCT00283049

Locations
United States, New Jersey
sanofi-aventis, US
Bridgewater, New Jersey, United States, 08807
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Lisa Jean-Louis Sanofi
  More Information

No publications provided

Responsible Party: Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00283049     History of Changes
Other Study ID Numbers: HOE901_4052
Study First Received: January 26, 2006
Results First Received: December 16, 2009
Last Updated: January 7, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
2,4-thiazolidinedione
Glargine
Insulin glulisine
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014