Lispro Mid Mixture (MM) Intensive Mixture Therapy With Progressive Dose-Titration of Lispro Low Mixture (LM) or Biphasic Insulin Aspart 30/70 (S019)

Official Title: “A Comparison of Insulin Lispro MM Intensive Mixture Therapy With Progressive Dose-Titration of Insulin Lispro LM or Biphasic Insulin Aspart 30/70”

Investigation into patients with type 2 diabetes mellitus not achieving adequate glycemic control while treated with combination of premixed insulin analogue formulations twice daily and metformin will be randomly assigned to follow one of two insulin treatment strategies used in combination with metformin administration. The aim of the trial is to try to achieve optimal metabolic control and explore full therapeutic potential of the strategies, patients in both arms will follow progressive insulin dose titration algorithms for 16 weeks.

Intervention(s) in this Clinical Trial

• Drug: Insulin Biphasic Aspart 30/70
  • Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks
• Drug: insulin lispro LM
  • Participant adjusted dose, injected subcutaneously for 16 weeks - possibility of using instead of insulin lispro MM before evening meal if there is a risk of hypoglycemia after the dinner or high fasting glucose levels.
• Drug: insulin lispro MM
  • Participant adjusted dose, three times per day, injected subcutaneously for 16 weeks
• Drug: insulin lispro LM
  • Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: insulin lispro LM + insulin lispro MM
  • Three times per day subcutaneous injection of insulin lispro mid mixture (MM) with the possibility to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved.
• Active Comparator: Insulin Biphasic Aspart 30/70 or Insulin Lispro LM
  • Twice daily subcutaneous injection of either insulin biphasic aspart 30/70 or insulin lispro low mixture (LM) (continuation of analogue formulation used before study enrollment).

Primary Measures

• Hemoglobin A1c (HbA1c) at 16 Week Endpoint
  • Time Frame: 16 weeks
    Safety Issue?: No

Secondary Measures

• Percentage of Patients Achieving Hemoglobin A1c (HbA1c) <7% and HbA1c ≤6.5% at 16 Week Endpoint
  • Time Frame: 16 weeks
    Safety Issue?: No
• Change From Baseline in Hemoglobin A1c (HbA1c) at 16 Week Endpoint
  • Time Frame: Baseline, 16 Weeks
    Safety Issue?: No
• 2-hour Postprandial Plasma Glucose Concentrations After the Midday Meal From Self-monitored 7-point Plasma Glucose at 16 Week Endpoint
  • Time Frame: 16 weeks
    Safety Issue?: No
• Mean 2-hour Postprandial Blood Glucose Excursions After Midday Meal at 16 Week Endpoint
  • Time Frame: 16 weeks
    Safety Issue?: No
• Mean Daily Blood Glucose Values at 16 Week Endpoint
  • Time Frame: 16 weeks
    Safety Issue?: No
• Number of Patients With Self-reported Hypoglycemic Episodes
  • Time Frame: Baseline through 16 weeks
    Safety Issue?: Yes
• 30-Day Adjusted Rate of Hypoglycemic Events
  • Time Frame: Baseline through 16 weeks
    Safety Issue?: Yes
• Change From Baseline in Weight at 16 Week Endpoint
  • Time Frame: Baseline, 16 weeks
    Safety Issue?: Yes
• Total Daily Insulin Dose at 4 Weeks and 12 Weeks
  • Time Frame: 4 weeks and 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Have type 2 diabetes (World Health Organization [WHO] classification).
• Are at least 30 years of age and less than 75 years of age.
• Have been receiving hypoglycemic treatment with premixed insulin analogue (either with insulin lispro LM or biphasic insulin aspart 30/70) administered twice daily in combination with at least 1500 milligrams (mg) of metformin per day for at least 60 days immediately prior to the study.
• Have a hemoglobin A1c 1.2 to 1.8 times the upper limit of the normal reference range at the local laboratory at Visit 1 or
• Have at least 6 of 9 of the postprandial blood glucose values recorded in the period between Visit 1 and Visit 2 exceeding 180 milligrams per 100 milliliters (mg/dl) (10.0 millimole per liter [mmol/l]).
• Have given written informed consent to participate in this study in accordance with local regulations.

Exclusion Criteria:

• Are taking any other oral anti-diabetic medication (OAM) not mentioned in inclusion criterion.
• Have a body mass index greater than 40 kilograms per meter squared (kg/m2).
• Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
• Have congestive heart failure.
• Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eli Lilly and Company Industry

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00393705

Study ID Number: 10916

ClinicalTrials.gov Identifier: NCT00393705

Health Authority: Poland: Ministry of Science and Higher Education

Lilly Clinical Trial Registry