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

Sanofi

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: insulin glulisine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00135083

HMR1964A_3511

Details and patient eligibility

About

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.

Enrollment: 347 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Subjects with type 2 diabetes mellitus who have been using a stable combination oral antidiabetic therapy of 2 or 3 agents in different therapeutic classes for on at least 3 months will be enrolled in this study.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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347 participants in 3 patient groups

1

Experimental group

Description:

Once daily: Insulin glulisine Dosing: Supper, Lunch, Breakfast Monitoring Needed at: Bedtime,Pre-Supper, Pre-Lunch

Treatment:

Drug: insulin glulisine

2

Experimental group

Description:

Twice daily: Insulin glulisine Dosing: Supper & Lunch, Lunch & Breakfast, Breakfast & Supper Monitoring Needed at: Bedtime & Pre-Supper, Pre-Supper & Pre-Lunch, Pre-Lunch & Bedtime

Treatment:

Drug: insulin glulisine

3

Experimental group

Description:

Twice daily: Insulin glulisine Dosing: Supper, Lunch, Breakfast Monitoring Needed at: Bedtime, Pre-Supper, Pre-Lunch

Treatment:

Drug: insulin glulisine