Variable Bolus Regimen 1-2-3 for Type 2 Diabetes Mellitus

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: insulin glulisine

• Registration Number: NCT00135083
• Lead Sponsor: Sanofi

Brief Summary

The purpose of this study is to show the non-inferiority of insulin glulisine administered with 1 meal versus 2 meals versus 3 daily meals, as measured by the change in hemoglobin A1c (HbA1c), from baseline to study week 24.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-08
• Study First Submitted: 2005-08-23
• Study First Submitted QC: 2005-08-24
• Study First Posted: 2005-08-25
• Study Completion: 2007-11
• Status Verified: 2011-01
• Last Update Submitted: 2011-01-10
• Last Update Posted: 2011-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 347

Inclusion Criteria

• Male and female subjects 18 to 79 years of age with a diagnosis of type 2 diabetes mellitus for at least 6 months

• Current treatment with a stable dose of 2 oral antidiabetic agents. The oral agents must be in 2 or 3 of the following 3 different classes:

  • Sulfonylurea: dosage greater than or equal to, one-half the maximum recommended dosage (eg, glimepiride >/= 4 mg; glipizide, including gastrointestinal therapeutic system [GITS], >/= 10 mg; glyburide >/= 10 mg; Glynase® >/=3 mg). The dosage must have been stable for at least 3 months prior to screening.
  • Biguanide: metformin dosage ≥ 1000 mg daily, including Glucophage XR®. The dosage must have been stable for at least 3 months prior to screening.
  • Thiazolidinedione (TZD): pioglitazone >/= 15 mg or rosiglitazone >/= 24 mg. The subject must have been using the same thiazolidinedione for at least 6 months,and the dosage must have been stable for at least 3 months prior to screening.

• HbA1c >/= 8.0%

• Fasting C-peptide concentration > 0.27 nmol/L

• Able and willing to perform self-monitoring of blood glucose (SMBG) up to 4 times a day

• Able and willing to adhere to, and be compliant with, the study protocol

• Able to read English or Spanish at the sixth-grade level in order to complete the subject reported outcomes component of the study

• Signed informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization

Exclusion Criteria

• Insulin use within the previous year
• History of hypoglycemia unawareness
• Acute or chronic, or history of, metabolic acidosis, including diabetic ketoacidosis
• Impaired renal function as shown by, but not limited to, serum creatinine ≥ 3mg/dL. For subjects taking metformin, serum creatinine >/= 1.5 mg/dL for males, or >/= 1.4 mg/dL for females.
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN)
• Clinically significant peripheral edema if subject is using a TZD
• History of stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris, within the past 12 months
• History of, or current, congestive heart failure (New York Heart Association [NYHA] III-IV) requiring pharmacologic treatment
• Acute infection
• Any malignancy within the past 5 years, with the exception of adequately treated basal or squamous cell carcinoma or adequately treated cervical carcinoma in situ
• Current substance addiction or alcohol abuse or history of substance or alcohol abuse, within the past 2 years
• Any clinically significant renal disease (other than proteinuria) or hepatic disease
• Pregnant or lactating females
• Dementia or mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
• Impaired dexterity or vision rendering the subject unable to administer injections
• Known hypersensitivity to insulin glargine or insulin glulisine or any of the components of Lantus or Apidra
• Any disease or condition (including abuse of illicit drugs, prescription medications, or alcohol) that, in the opinion of the investigator or sponsor, may interfere with the completion of the study
• Unlikely to comply with the protocol, eg, uncooperative attitude, inability to return for follow-up visits, or unlikely to complete the study
• 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
• No subject will be allowed to enroll in this study more than once.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	insulin glulisine	Twice daily: * Insulin glulisine Dosing: Supper \& Lunch, Lunch \& Breakfast, Breakfast \& Supper * Monitoring Needed at: Bedtime \& Pre-Supper, Pre-Supper \& Pre-Lunch, Pre-Lunch \& Bedtime
1	insulin glulisine	Once daily: * Insulin glulisine Dosing: Supper, Lunch, Breakfast * Monitoring Needed at: Bedtime,Pre-Supper, Pre-Lunch
3	insulin glulisine	Twice daily: * Insulin glulisine Dosing: Supper, Lunch, Breakfast * Monitoring Needed at: Bedtime, Pre-Supper, Pre-Lunch

Primary Outcome Measures

Name	Time	Method
To show non-inferiority between treatment groups (insulin glargine plus insulin glulisine administered once a day, twice a day, or 3 times a day) in the change in glycemic control as measured by hemoglobin A1C.	From baseline to study week 24.