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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

One Versus Two Versus Three Daily Rapid-acting Insulin Injections of APIDRA (Insulin Glulisine) as add-on to Lantus® and Oral Sensitizer Basal Therapy in Type 2 Diabetes: a Multicenter, Randomized, Parallel, Open-label Clinical Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00135083
• Other study ID #: HMR1964A_3511
• Status: Completed
• Phase: Phase 3
• First received: August 23, 2005
• Last updated: January 10, 2011
• Start date: August 2004
• Est. completion date: November 2007

Study information

• Verified date: January 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 347
• Est. completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No