Comparison of Two Basal Insulin Therapies for Patients With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to examine the efficacy and safety of insulin lispro protamine suspension (ILPS) as compared to insulin detemir as basal insulin combined with mealtime insulin therapy in patients with type 1 diabetes. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.

Detailed Description
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Phase 3b, randomized, multicenter, multinational, open-label, two-arm, active control, parallel study to determine safety, efficacy, and noninferiority of basal analog insulin lispro protamine suspension (ILPS, also referred to as NPL [neutral protamine Hagedorn]), injected two times a day, compared with basal analog insulin detemir, injected two times a day, as measured by change in hemoglobin A1c (HbA1c) from baseline (Visit 2) to 32 weeks in adult patients with type 1 diabetes when used in combination with bolus insulin lispro, injected three times a day.

Official Title
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Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Insulin Detemir) in Basal-Bolus Therapy for Patients With Type 1 Diabetes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Insulin Lispro Protamine Suspension
* Drug: Insulin Levemir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 1 diabetes for one year or more Age 18 years or older Body mass index (BMI) less than or equal to 35 kilograms per square meter (kg/m2) Have a hemoglobin A1c (HbA1c) 1.2 to 2.0 times the upper limit of the normal (ULN) reference range within 30 days prior to Visit 1 or collected and analyzed at a local laboratory at Visit 1 As determined by the investigator, are capable and willing to do the following: perform self monitoring of blood glucose (SMBG), complete patient diaries as required for this protocol, use the insulin injection device(s) according to the instructions provided, are receptive to diabetes education, comply with the required study visits. Exclusion Criteria: Have taken any oral antihyperglycemic medications (OAMs) within 3 months prior to Visit 1. Have had more than one episode of severe hypoglycemia, as defined in the Abbreviations and Definitions section of the protocol, within 6 months prior to entry into the study Are 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 or women who are breastfeeding Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, intraocular, and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding Visit 1. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Lispro Protamine Suspension<br>Insulin Lispro Protamine Suspension twice daily | Drug: Insulin Lispro Protamine Suspension<br>* Patient specific dose, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks.<br>* Other names: LY275585;|
| Active Comparator: Detemir<br>Insulin Levemir (detemir) subcutaneous (SC) twice daily. | Drug: Insulin Levemir<br>* Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint |  | baseline and 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values | The summary statistics represents the mean of all subjects. Change from baseline is calculated for each individual subject for the specific visit and then the mean change from baseline is calculated by averaging out for all subjects. [Sum over all (i) {A1c at Week 8 for Subject(i) minus A1c Baseline for Subject (i)}/Total Subjects]. Therefore, for example, the Change from Baseline is not equal to the difference of Mean A1c for Week 8 minus Mean A1c for baseline. | Baseline, 8,16, 24, 32 Weeks | 
| Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5% |  | 32 Weeks | 
| 7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint | Actual daily mean blood glucose levels at endpoint. The SMBG excursion is the difference between the postprandial and preprandial blood glucose concentration taken at the morning, midday and evening meals. | 32 Weeks | 
| Glycemic Variability at Endpoint | Glycemic variability was measured by standard deviation (SD) value of fasting blood glucose as measured by intra-patient glycemic variability (determined by the 7-point self-monitored blood glucose [SMBG] profiles at endpoint); mean value (M-value), which was the mean of the intra-days self-monitored blood glucose values, and by the mean of daily difference (MODD), which was the mean of the between-days self-monitored blood glucose values. | 32 Weeks | 
| Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint | Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of <2.8 mmol/L (<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose. | Baseline to 32 Weeks | 
| 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint | Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of <2.8 mmol/L (<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose. | baseline to 32 weeks | 
| 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint |  | baseline to 32 weeks | 
| Change From Baseline in Absolute Body Weight at 32 Week Endpoint |  | Baseline, 32 Weeks | 
| Insulin Dose Per Body Weight (Total and By Component [Basal and Bolus]) | Total daily insulin dose adjusted for body weight (U/kg/day) was assessed. | 32 Weeks | 
| Insulin Dose (Total and By Component [Basal and Bolus]) | Total daily insulin dose (U/day) was assessed. | 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, type 1