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

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

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

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin Glargine; Drug: Insulin Glulisine

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • sanofi-aventis, US

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12	12 weeks from Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Individual Time Points in HbA1c, Insulin Doses, and Total Insulin Dosage		60 weeks from Baseline
Percentage of Subjects Achieving an HbA1C Less Than (<) 7.0% and Less Than (<) 6.5%		60 weeks from Baseline
Change From Baseline to Study Time Points in 7-point Blood Glucose (BG) Profile (Before Meals, 2 Hours After Meals, at Bedtime)		60 weeks from Baseline
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)		60 weeks from Baseline
Occurrences of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia, and Serious Hypoglycemia	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, orwith prompt response to treatment with oral carbohydrates, IV glucose or glucagon.; Serious hypoglycemia:Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion.	60 weeks from Baseline
Rate of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia and Serious Hypoglycemia	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, orwith prompt response to treatment with oral carbohydrates, IV glucose or glucagon.; Serious hypoglycemia:Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion.	60 Weeks from Baseline

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Lisa Jean-Louis, Sanofi

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: January 26, 2006
• First Submitted That Met QC Criteria: January 26, 2006
• First Posted (Estimate): January 27, 2006

Study Record Updates

• Last Update Posted (Estimate): January 13, 2011
• Last Update Submitted That Met QC Criteria: January 7, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin glulisine
• Other Study ID Numbers: HOE901_4052