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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

Primary Purpose

Diabetes Mellitus, Type 2

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Insulin Glargine
Insulin Glulisine
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects meeting all of the following criteria will be considered for enrollment into the study: 18 to 79 years of age, inclusive Diagnosis of type 2 diabetes mellitus Continuous treatment with therapeutic dosages of a thiazolidinedione (rosiglitazone or pioglitazone), metformin, and a sulfonylurea daily prior to entering the study Screening HbA1c ≥ 7.0% Fasting C-peptide concentration ≥ 0.27 ng/ml Negative glutamic acid decarboxylase (GAD) antibodies Demonstrated ability and willingness to perform self-monitoring blood glucose (SMBG) using a plasma-referenced glucose meter and to maintain an electronic diary Demonstrated ability and willingness to use an electronic diary to record SMBG results, insulin doses, and hypoglycemic events. Signed, informed consent and Health Insurance Portability and Accountability Act (HIPAA) documentation Exclusion Criteria: Stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris, within the last 12 months Cardiac status New York Heart Association (NYHA) III-IV 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 Chronic use of insulin: (more than 3 weeks of continuous use) in the past 12 months Acute infection Clinically significant peripheral edema Acute or chronic history of metabolic acidosis, including diabetic ketoacidosis 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 History of hypoglycemia unawareness Pregnancy or lactation Known hypersensitivity to insulin glargine or any of the components of Lantus® Known hypersensitivity to insulin glulisine or any of the components of Apidra® 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 Current addiction or current alcohol abuse, or history of substance or alcohol abuse within the last 2 years Diagnosis of dementia 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 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 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) Any disease or condition that in the opinion of the investigator and/or sponsor may interfere with the completion of the study

Sites / Locations

  • sanofi-aventis, US

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Insulins + Sulfonylurea (SU) + Thiazolidinedione (TZD)

Insulins + Metformin (MET) + Thiazolidinedione (TZD)

Insulins + Metformin (MET) + Sulfonylurea (SU)

Arm Description

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%)

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%)

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%)

Outcomes

Primary Outcome Measures

Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12

Secondary Outcome Measures

Change From Baseline to Individual Time Points in HbA1c, Insulin Doses, and Total Insulin Dosage
Percentage of Subjects Achieving an HbA1C Less Than (<) 7.0% and Less Than (<) 6.5%
Change From Baseline to Study Time Points in 7-point Blood Glucose (BG) Profile (Before Meals, 2 Hours After Meals, at Bedtime)
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)
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.
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.

Full Information

First Posted
January 26, 2006
Last Updated
January 7, 2011
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00283049
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2011
Overall Recruitment Status
Terminated
Why Stopped
Due to technical issues relating to the Electronic diary data.
Study Start Date
February 2006 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Sanofi

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
390 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Insulins + Sulfonylurea (SU) + Thiazolidinedione (TZD)
Arm Type
Experimental
Arm Description
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%)
Arm Title
Insulins + Metformin (MET) + Thiazolidinedione (TZD)
Arm Type
Experimental
Arm Description
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%)
Arm Title
Insulins + Metformin (MET) + Sulfonylurea (SU)
Arm Type
Experimental
Arm Description
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%)
Intervention Type
Drug
Intervention Name(s)
Insulin Glargine
Intervention Description
Insulin glargine administered subcutaneously once daily.
Intervention Type
Drug
Intervention Name(s)
Insulin Glulisine
Intervention Description
Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)
Primary Outcome Measure Information:
Title
Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12
Time Frame
12 weeks from Baseline
Secondary Outcome Measure Information:
Title
Change From Baseline to Individual Time Points in HbA1c, Insulin Doses, and Total Insulin Dosage
Time Frame
60 weeks from Baseline
Title
Percentage of Subjects Achieving an HbA1C Less Than (<) 7.0% and Less Than (<) 6.5%
Time Frame
60 weeks from Baseline
Title
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
Title
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
Title
Occurrences of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia, and Serious Hypoglycemia
Description
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.
Time Frame
60 weeks from Baseline
Title
Rate of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia and Serious Hypoglycemia
Description
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.
Time Frame
60 Weeks from Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects meeting all of the following criteria will be considered for enrollment into the study: 18 to 79 years of age, inclusive Diagnosis of type 2 diabetes mellitus Continuous treatment with therapeutic dosages of a thiazolidinedione (rosiglitazone or pioglitazone), metformin, and a sulfonylurea daily prior to entering the study Screening HbA1c ≥ 7.0% Fasting C-peptide concentration ≥ 0.27 ng/ml Negative glutamic acid decarboxylase (GAD) antibodies Demonstrated ability and willingness to perform self-monitoring blood glucose (SMBG) using a plasma-referenced glucose meter and to maintain an electronic diary Demonstrated ability and willingness to use an electronic diary to record SMBG results, insulin doses, and hypoglycemic events. Signed, informed consent and Health Insurance Portability and Accountability Act (HIPAA) documentation Exclusion Criteria: Stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris, within the last 12 months Cardiac status New York Heart Association (NYHA) III-IV 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 Chronic use of insulin: (more than 3 weeks of continuous use) in the past 12 months Acute infection Clinically significant peripheral edema Acute or chronic history of metabolic acidosis, including diabetic ketoacidosis 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 History of hypoglycemia unawareness Pregnancy or lactation Known hypersensitivity to insulin glargine or any of the components of Lantus® Known hypersensitivity to insulin glulisine or any of the components of Apidra® 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 Current addiction or current alcohol abuse, or history of substance or alcohol abuse within the last 2 years Diagnosis of dementia 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 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 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) Any disease or condition that in the opinion of the investigator and/or sponsor may interfere with the completion of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa Jean-Louis
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
sanofi-aventis, US
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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