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

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00393705
First received: October 26, 2006
Last updated: July 15, 2010
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Insulin Biphasic Aspart 30/70
Drug: insulin lispro LM
Drug: insulin lispro MM
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Hemoglobin A1c (HbA1c) at 16 Week Endpoint [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Patients Achieving Hemoglobin A1c (HbA1c) <7% and HbA1c ≤6.5% at 16 Week Endpoint [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in Hemoglobin A1c (HbA1c) at 16 Week Endpoint [ Time Frame: Baseline, 16 Weeks ] [ Designated as 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 ] [ Designated as safety issue: No ]
    Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the blood glucose concentrations 2-hours after the midday meal at Week 16.

  • Mean 2-hour Postprandial Blood Glucose Excursions After Midday Meal at 16 Week Endpoint [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the difference (excursion) between midday premeal and 2-hour postprandial midday meal blood glucose concentrations at Week 16.

  • Mean Daily Blood Glucose Values at 16 Week Endpoint [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Number of Patients With Self-reported Hypoglycemic Episodes [ Time Frame: Baseline through 16 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.

  • 30-Day Adjusted Rate of Hypoglycemic Events [ Time Frame: Baseline through 16 weeks ] [ Designated as safety issue: Yes ]
    Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.

  • Change From Baseline in Weight at 16 Week Endpoint [ Time Frame: Baseline, 16 weeks ] [ Designated as safety issue: Yes ]
  • Total Daily Insulin Dose at 4 Weeks and 12 Weeks [ Time Frame: 4 weeks and 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 302
Study Start Date: October 2006
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Other Names:
  • Low Mix
  • Humalog
Drug: insulin lispro MM
Participant adjusted dose, three times per day, injected subcutaneously for 16 weeks
Other Names:
  • Mid Mix
  • Humalog
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).
Drug: Insulin Biphasic Aspart 30/70
Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks
Drug: insulin lispro LM
Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks
Other Names:
  • Low Mix
  • Humalog

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00393705

Locations
Croatia
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Zagreb, Croatia, HR-10000
Poland
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Bialystok, Poland, 15-276
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Rzeszow, Poland, 35-0723
Romania
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Bucharest, Romania, 020475
South Africa
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kempton Park, South Africa, 1619
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kenilworth, South Africa, 7708
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Kuilsriver, South Africa, 7580
Turkey
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Istanbul, Turkey, 34662
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Konya, Turkey, 42075
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

Additional Information:
No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00393705     History of Changes
Other Study ID Numbers: 10916, F3Z-VI-S019
Study First Received: October 26, 2006
Results First Received: March 31, 2010
Last Updated: July 15, 2010
Health Authority: Poland: Ministry of Science and Higher Education

Keywords provided by Eli Lilly and Company:
diabetes
type 2

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

ClinicalTrials.gov processed this record on April 15, 2014