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

NCT ID: NCT00135083

Last Updated: 2011-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 347 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2007-11-30

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Once daily:

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

Group Type: EXPERIMENTAL

insulin glulisine

Intervention Type: DRUG

• Once Daily Insulin: Subjects will receive insulin glulisine administered once daily 0-15 minutes before the greatest glycemic impact meal of the day starting at one-tenth the total dose of insulin glargine with maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Twice Daily: Subjects will receive insulin glulisine administered twice daily 0-15 minutes before the 2 greatest glycemic impact meals of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Three Times Daily: Subjects will receive insulin glulisine administered 3 times daily 0-15 minutes before each meal of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units for each meal and additional monitoring as shown in the table below.

2

Twice daily:

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

Group Type: EXPERIMENTAL

insulin glulisine

Intervention Type: DRUG

• Once Daily Insulin: Subjects will receive insulin glulisine administered once daily 0-15 minutes before the greatest glycemic impact meal of the day starting at one-tenth the total dose of insulin glargine with maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Twice Daily: Subjects will receive insulin glulisine administered twice daily 0-15 minutes before the 2 greatest glycemic impact meals of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Three Times Daily: Subjects will receive insulin glulisine administered 3 times daily 0-15 minutes before each meal of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units for each meal and additional monitoring as shown in the table below.

3

Twice daily:

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

Group Type: EXPERIMENTAL

insulin glulisine

Intervention Type: DRUG

• Once Daily Insulin: Subjects will receive insulin glulisine administered once daily 0-15 minutes before the greatest glycemic impact meal of the day starting at one-tenth the total dose of insulin glargine with maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Twice Daily: Subjects will receive insulin glulisine administered twice daily 0-15 minutes before the 2 greatest glycemic impact meals of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Three Times Daily: Subjects will receive insulin glulisine administered 3 times daily 0-15 minutes before each meal of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units for each meal and additional monitoring as shown in the table below.

Interventions

insulin glulisine

• Once Daily Insulin: Subjects will receive insulin glulisine administered once daily 0-15 minutes before the greatest glycemic impact meal of the day starting at one-tenth the total dose of insulin glargine with maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Twice Daily: Subjects will receive insulin glulisine administered twice daily 0-15 minutes before the 2 greatest glycemic impact meals of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units, and with additional monitoring as shown in the table below.
• Three Times Daily: Subjects will receive insulin glulisine administered 3 times daily 0-15 minutes before each meal of the day starting at one-tenth the total dose of insulin glargine with a maximum starting dose of 10 Units for each meal and additional monitoring as shown in the table below.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

sanofi-aventis

Principal Investigators

Karen Barch, B.S.

Role: STUDY_DIRECTOR

Sanofi

References

Davidson MB, Raskin P, Tanenberg RJ, Vlajnic A, Hollander P. A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure. Endocr Pract. 2011 May-Jun;17(3):395-403. doi: 10.4158/EP10323.OR.

Reference Type: DERIVED

PMID: 21324825 (View on PubMed)

Other Identifiers

HMR1964A_3511

Identifier Type: -

Identifier Source: org_study_id