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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00283049
• Other study ID #: HOE901_4052
• Status: Terminated
• Phase: Phase 4
• First received: January 26, 2006
• Last updated: January 7, 2011
• Start date: February 2006
• Est. completion date: November 2008

Study information

• Verified date: January 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 390
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Insulin Glargine
Insulin glargine administered subcutaneously once daily.
• Insulin Glulisine
Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)

Locations

Country	Name	City	State
United States	sanofi-aventis, US	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12		12 weeks from Baseline	No
Secondary	Change From Baseline to Individual Time Points in HbA1c, Insulin Doses, and Total Insulin Dosage		60 weeks from Baseline	No
Secondary	Percentage of Subjects Achieving an HbA1C Less Than (<) 7.0% and Less Than (<) 6.5%		60 weeks from Baseline	No
Secondary	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	No
Secondary	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	No
Secondary	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, 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.	60 weeks from Baseline	Yes
Secondary	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, 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.	60 Weeks from Baseline	Yes