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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00135083
First received: August 23, 2005
Last updated: January 10, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: insulin glulisine
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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. [ Time Frame: From baseline to study week 24. ] [ Designated as safety issue: No ]

Enrollment: 347
Study Start Date: August 2004
Study Completion Date: November 2007
Arms Assigned Interventions
Experimental: 1

Once daily:

  • Insulin glulisine Dosing: Supper, Lunch, Breakfast
  • Monitoring Needed at: Bedtime,Pre-Supper, Pre-Lunch
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.
Experimental: 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
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.
Experimental: 3

Twice daily:

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

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00135083

Sponsors and Collaborators
Sanofi
Investigators
Study Director: Karen Barch, B.S. Sanofi
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00135083     History of Changes
Other Study ID Numbers: HMR1964A_3511
Study First Received: August 23, 2005
Last Updated: January 10, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin glulisine
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014