Insulin Lispro 6 Days Versus Insulin Aspart 6 Days in Pump Use

Study Overview
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Brief Summary
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This is a 6-sequence, 3-period (8 weeks each), 3-arm, 24-week crossover study. The purpose of this study is to provide information on the use of insulin lispro in insulin pumps (Continuous Subcutaneous Insulin Infusion [CSII]) compared to insulin aspart over 6 days of pump reservoir in-use. The study will also compare the in-use characteristics of insulin lispro infused at 6 days with insulin lispro infused at 2 days.

Official Title
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An Open-Label, Randomized, Crossover Trial of CSII Reservoir In-use Comparing Insulin Lispro Formulation to Insulin Aspart in Patients With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Insulin lispro 2 day reservoir in-use
* Drug: Insulin lispro 6 day reservoir in-use
* Drug: Insulin aspart 6 day reservoir in-use


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 1 diabetes (World Health Organization criteria) for at least 24 months. Treated with continuous subcutaneous insulin infusion therapy for the previous 6 months. Mean total daily insulin dose for 3 days prior to screening equal to or less than 46 units/day using a 300-unit reservoir or less than or equal to 26 units/day using a 180 unit reservoir. Baseline body mass index (BMI) less than or equal to 35.0 kg/m^2. Baseline glycosylated hemoglobin (HbA1c) 5% to 9%. Exclusion Criteria: Impaired renal function (serum creatinine greater than or equal to 2.0 milligrams per deciliter [mg/dL]). Legal blindness. Have had any episode of hypoglycemic coma, seizures, or disorientation in the 12 months prior to screening. Have had hypoglycemia unawareness (routinely asymptomatic at blood glucose (BG) less than 45 mg/dL) in the 12 months prior to screening. Have had any emergency room visits or hospitalizations due to poor glucose control in the 12 months prior to screening. Have had a pump-related infusion site abscess in the 12 months prior to screening. Have had multiple, clinically significant occlusions as judged by the investigator. Have had any infection with staphylococcus aureus in the past 5 years. Have one of the following concomitant diseases: presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease, or any other serious disease considered by the investigator to be exclusionary. Patients with malignancy other than basal cell or squamous cell skin cancer who have not yet been treated, are currently being treated, or who were diagnosed less than 5 years ago. Have had a blood transfusion or severe blood loss within 3 months prior to screening, or have known hemoglobinopathy, hemolytic anemia or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with HbA1c methodology. Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, intraocular and inhaled prescriptions), or have received such therapy within the 4 weeks immediately preceding screening. Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night), in the investigator's opinion. Have known hypersensitivity or allergy to any of the study insulins or their excipients. Are breastfeeding or pregnant, or intend to become pregnant during the course of the study, or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable. Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Have previously completed or withdrawn from this study after having signed the informed consent document (ICD). Are unwilling or unable to comply with the use of a data collection device to directly record data from the patient.

Ages Eligible for Study
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Minimum Age: 13 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin Lispro 2 Day<br> | Drug: Insulin lispro 2 day reservoir in-use<br>* Insulin lispro 2 Day (L2D) administered by infusion pump for 8 week treatment period.<br>* Other names: Humalog;|
| Experimental: Insulin Lispro 6 Day<br> | Drug: Insulin lispro 6 day reservoir in-use<br>* Insulin lispro 6 Day (L6D) administered by infusion pump for 8 week treatment period.<br>* Other names: Humalog;|
| Active Comparator: Insulin Aspart 6 Day<br> | Drug: Insulin aspart 6 day reservoir in-use<br>* Insulin aspart 6 Day (A6D) administered by infusion pump for 8 week treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of Last Five 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Day 2 for Insulin Lispro 2D and Day 6 for Insulin Aspart 6D Pump Reservoir In-use |  | 8 weeks of each treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean SMBG | Mean SMBG for combined periods; all reported SMBG values on days 1-6 for Insulin Lispro 6 Day and Insulin Aspart 6 Day, and days 1-2 for Insulin Lispro 2 Day. | 8 weeks for each treatment | 
| Mean Daily Insulin Dose (Total, Basal, and Bolus) |  | 8 weeks for each treatment | 
| Change From Baseline to 8 Weeks Endpoint for Each Treatment in Hemoglobin A1c (HbA1c) Values |  | Baseline, 8 weeks for each treatment | 
| Number of Participants Who Achieve or Maintain an HbA1c Less Than or Equal to 6.5% and Less Than 7% |  | 8 weeks for each treatment | 
| Percentage of Participants With Hyperglycemia | Hyperglycemia was defined as an event with (1) a measured blood glucose concentration >250 milligrams per deciliter (mg/dL) (13.9 mmol/L) and ≥3 hours after eating, or (2) a measured blood glucose concentration >300 mg/dL (16.7 mmol/L) and <3 hours after eating. | 8 weeks for each treatment | 
| Hyperglycemic Episode Rate Per 30 Days | Hyperglycemia was defined as an episode with (1) a measured blood glucose concentration >250 milligrams per deciliter (mg/dL) (13.9 mmol/L) and ≥3 hours after eating, or (2) a measured blood glucose concentration >300 mg/dL (16.7 mmol/L) and <3 hours after eating. Rate is presented as the number of hyperglycemic episodes adjusted for 30 days. | 8 weeks for each treatment | 
| Percentage of Participants With Pump Complications | Overall Pump Complications were any combination of: tubing clogged, kinked, disconnected, pulled out, blood in tubing; too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm; at site - skin abscess, excessive redness, swelling (not nodule), bleeding, bruising; reservoir change (infusion set change reason only); and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether change was early (prior to 6 days for L6D or A6D, or prior to 2 days for L2D). If 'yes', then recorded as premature change. | 8 weeks for each treatment | 
| Pump Complication Rate Per 30 Days | Overall Pump Complications were any combination of: tubing clogged, kinked, disconnected, pulled out, blood in tubing; too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm; at site - skin abscess, excessive redness, swelling (not nodule), bleeding, bruising; reservoir change (infusion set change reason only); and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether change was early (prior to 6 days for L6D or A6D, or prior to 2 days for L2D). If 'yes', then recorded as premature change. | 8 weeks for each treatment | 
| Percentage of Participants With Hypoglycemia | Hypoglycemia was defined as an event which was associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of ≤ 70 mg/dL (3.9 mmol/L). | 8 weeks for each treatment | 
| Hypoglycemia Episode Rate Per 30 Days | Hypoglycemia was defined as an event which was associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of ≤ 70 mg/dL (3.9 mmol/L). Rate is presented as the number of hypoglycemic episodes adjusted for 30 days. | 8 weeks for each treatment | 
| Change From Baseline to 8 Weeks Endpoint for Each Treatment in Weight |  | Baseline, 8 weeks for each treatment | 
| Change From Baseline to 8 Weeks Endpoint for Each Treatment in Blood Pressure |  | Baseline, 8 weeks for each treatment |