Safety and Efficacy Study of Insulin Lispro Versus Insulin Aspart in Participants With Type 2 Diabetes on Insulin Pump Therapy

A Randomized, Double-Blind, Crossover Trial Comparing the Safety and Efficacy of Insulin Lispro With the Safety and Efficacy of Insulin Aspart in Subjects With Type 2 Diabetes on CSII Therapy

This study will provide information on the use of insulin lispro and insulin aspart in insulin pumps in participants with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin Lispro; Drug: Insulin Aspart

Detailed Description

This study will provide clinical information on the use of insulin lispro in continuous subcutaneous insulin infusion (CSII) in participants with type 2 diabetes. This study is designed to allow comparison of the 2 rapid-acting insulin analogs, with regard to their efficacy and safety, when used as a pump insulin therapy in this participant population. Each participant will be randomized to 1 of the 2 sequence groups in a 1:1 ratio and randomization will be stratified according to screening A1C (less than or equal to 8.0% or greater than 8.0%) and thiazolidinedione (TZD) use (yes or no). The study design includes the following periods: Screening/Randomization, Treatment Period 1 (16 weeks), and Treatment Period 2 (16 weeks).

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • 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.
  • Florida
    • Jacksonville, Florida, United States, 32216
      • 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.
    • West Palm Beach, Florida, United States, 33401
      • 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.
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • 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.
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • 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.
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • 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.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • 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.
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • 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.
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • 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.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • 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.
  • Texas
    • Austin, Texas, United States, 78731
      • 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.
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have type 2 diabetes (per World Health Organization [WHO] Classification of Diabetes)
• Have been treated with CSII therapy using a rapid-acting analog for the previous 6 months
• Have a screening A1C less than or equal to 9.0% (no lower limit for A1C)
• Have a body mass index (BMI) less than 45 kilograms/square meter (kg/m²) at screening
• Have a history of stable body weight (not varying by greater than 10% for at least 3 months prior to screening)
• For participants on oral anti-diabetes medications (OAMs): must have been on a stable dose of OAMs, labeled for use with insulin, for at least 3 months prior to study entry

Exclusion Criteria:

• Have severe insulin resistance [require greater than 2 units/kilogram/day (U/kg/day) of insulin]
• Are taking or have taken within the last 3 months, antihyperglycemic medication not approved for use with insulin, injectable non-insulin antihyperglycemic medications, or have a contraindication to current antihyperglycemic medication
• Have a serum creatinine greater than or equal to 2 milligrams/deciliter (mg/dL) if not on metformin; known metabolic or lactic acidosis; any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis; and/or a radiologic contrast study within 48 hours prior to study entry
• Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, intraarticular, and inhaled preparations) or have received such therapy within 2 weeks immediately before screening
• Have had more than 1 episode of hypoglycemia (defined as requiring assistance of a third party due to disabling hypoglycemia) within 6 months prior to entry into the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Insulin Lispro, then Insulin Aspart; Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1, followed by insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2.	Drug: Insulin Lispro; Insulin lispro (100 U/mL) administered by CSII pump; Other Names: Humalog; LY275585
ACTIVE_COMPARATOR: Insulin Aspart, then Insulin Lispro; Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1, followed by insulin lispro (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2.	Drug: Insulin Aspart; Insulin aspart (100 U/mL) administered by CSII pump; Other Names: Novolog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycosylated Hemoglobin A1C (HbA1c) at Endpoint	Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over the last 8-12 weeks. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline HbA1c (>8% or ≤8%) and participants.	After 16 weeks of each treatment (Periods1 and 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Daily Insulin Dose	Total daily insulin dose was the average of the last 3 days total insulin dose immediately prior to the Week 16 (endpoint) visit of each treatment period. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%) and participants.	Week 16 of each treatment (Periods 1 and 2)
Rate of Hypoglycemic Events Per 30 Days	A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]. Least Squares (LS) means were adjusted for treatment, period, sequence, baseline hypoglycemic event rate, thiazolidinedione use (Yes/No) and baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%).	Baseline through 16 weeks of each treatment (Periods 1 and 2)
Change From Baseline in Weight	Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%), baseline weight and participants.	Baseline, Week 16 of treatment Periods 1 and 2
Percentage of Participants With Hypoglycemic Events	A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]. The percentage of participants is the total number of participants experiencing hypoglycemic events divided by number of participants in the treatment arm multiplied by 100.	Baseline through 16 weeks of each treatment (Periods 1 and 2)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (ESTIMATE): November 18, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 20, 2014
• Last Update Submitted That Met QC Criteria: February 4, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: diabetes; type 2 diabetes; insulin pump; CSII; continuous subcutaneous insulin infusion; A1C
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Lispro
• Other Study ID Numbers: 14207; F3Z-MC-IOQH (OTHER: Eli Lilly and Company)