Comparison of Two Basal Insulins for Patients With Type 2 Diabetes (IOOY)

Study Overview
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Brief Summary
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The purpose of this study is to examine the effectiveness and safety of insulin lispro protamine suspension (ILPS) as compared to insulin detemir as basal insulin therapy in adults with type 2 diabetes. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.

Official Title
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Treat-to-Target Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Comparator) in Basal Therapy for Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have type 2 diabetes mellitus for at least 1 year. Are at least 18 years old. Have been receiving oral antihyperglycemic medications (OAMs), without insulin, for at least 3 months immediately prior to the study and have been on stable doses of at least 2 of the following OAMs for the 6 weeks prior to Visit 1, at or above the doses defined in the following: Metformin--1500 milligrams per day (mg/day); Sulfonylureas--1/2 the maximum daily dose, according to the local package insert; Dipeptidyl peptidase-intravenous (DPP-IV) inhibitors-- 1/2 the maximum daily dose, according to the local package insert; Thiazolidinediones (TZDs)--30 mg/day pioglitazone or 4 mg/day rosiglitazone. Have a hemoglobin A1c (HbA1c) greater than or equal to 7.5% and less than or equal to 10.0%, as measured by a central laboratory before Visit 2. Body mass index (BMI) greater than or equal to 25 and less than or equal to 45 kilograms per square meter (kg/m2). Exclusion Criteria Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks. Have taken any glucose-lowering medications not included in Inclusion Criterion [3] (for example, acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide) in the past 3 months before Visit 1. Have had more than 1 episode of severe hypoglycemia, within 6 months prior to entry into the study, or is currently diagnosed as having hypoglycemia unawareness. Have a history of renal transplantation or are currently receiving renal dialysis or creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL) (177 micromoles per liter [micromol/L]). Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease (alanine transaminase [ALT], or aspartate transaminase [AST] greater than 2 times the upper limit of the reference range, as defined by the local laboratory) or have albumin value above or below the normal reference range, as defined by the local laboratory.

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: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. | Drug: Insulin Lispro Protamine Suspension<br>* Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks.<br>* Other names: ILPS;|
| Active Comparator: Detemir<br>Detemir: Patient specific dose administered subcutaneously once or twice daily x 24 weeks. | Drug: Detemir<br>* Patient specific dose administered subcutaneously once or twice daily x 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) |  | Baseline, 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks |  | Baseline, 12 Weeks, 24 Weeks | 
| Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint | Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7.0% and less than or equal to 6.5% at endpoint. | 24 Weeks | 
| Glycemic Variability | 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-monitoring blood glucose [SMBG] profiles at endpoint) for the actual morning pre-meal blood glucose value. | 24 Weeks | 
| 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Actual daily mean blood glucose levels at endpoint. | 24 Weeks | 
| Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. Results are for the combined titration and maintenance periods. | Baseline to 24 Weeks | 
| 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 1-year adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 365.25 days. | Baseline to 24 Weeks | 
| 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 30-day adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 30 days. | Baseline to 24 Weeks | 
| Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint |  | Baseline, 24 Weeks | 
| Total Daily Insulin Dose (Units) at Endpoint | Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units). | 24 Weeks | 
| Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint | Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (Units/kilograms). | 24 Weeks | 
| Number of Injections of Basal Insulin Analog at Endpoint |  | 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, type 2