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

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

Detailed Description
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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).

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin Lispro
* Drug: Insulin Aspart


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin Lispro, then Insulin Aspart<br>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<br>* Insulin lispro (100 U/mL) administered by CSII pump<br>* Other names: LY275585;|
| Active Comparator: Insulin Aspart, then Insulin Lispro<br>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<br>* Insulin aspart (100 U/mL) administered by CSII pump<br>* Other names: Novolog;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CSII, diabetes, type 2 diabetes, insulin pump, continuous subcutaneous insulin infusion, A1C