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

Sanofi

Status and phase: Terminated; Phase 4

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Insulin Glulisine; Drug: Insulin Glargine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00283049

HOE901_4052

Details and patient eligibility

About

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

Enrollment: 390 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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390 participants in 3 patient groups

Insulins + Sulfonylurea (SU) + Thiazolidinedione (TZD)

Experimental group

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%)

Treatment:

Drug: Insulin Glulisine

Drug: Insulin Glargine

Insulins + Metformin (MET) + Thiazolidinedione (TZD)

Experimental group

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%)

Treatment:

Drug: Insulin Glulisine

Drug: Insulin Glargine

Insulins + Metformin (MET) + Sulfonylurea (SU)

Experimental group

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%)

Treatment:

Drug: Insulin Glulisine

Drug: Insulin Glargine