A Study of Insulin Lispro Mix in Type 2 Diabetic Asian Patients

Study Overview
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Brief Summary
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The purpose is to evaluate the proportion of subjects achieving a Hemoglobin A1c (HbA1c) level below 6.5%, when lispro mix 50/50 is introduced in a stepwise manner from every day (QD) administration to type 2 diabetic patients who have failed to achieve adequate glycemic control on oral antidiabetic drugs (OADs).

Detailed Description
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A multicenter, non-randomized, open-label, post-marketing clinical study. The target population of the study is type 2 diabetic patients who have failed to achieve adequate glycemic control on OADs. The study consists of 4 periods: Lead-in Period (2 to 4 weeks), Study Period I (16 weeks), Study Period II (16 weeks), and Study Period III (16 weeks). The regimen of lispro mix 50/50 injection will be changed every 16 weeks based on the HbA1c level. During Study Period I, all the subjects will be given a once daily (QD) injection of lispro mix 50/50. During Study Period II, the regimen of lispro mix 50/50 injection will be changed to twice daily (BID) if the HbA1c level at Week 16 is 6.5% or above, and QD injection will be continued if the value is below 6.5%. During Study Period III, if the HbA1c level at Week 32 is 6.5% or above, the subjects on BID treatment during the previous period (Study Period II) will receive three times daily (TID) injections of insulin.

Official Title
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The Study of Stepwise Introduction of Insulin Analog Mixture as a Post-marketing Clinical Trial of Lispro Mix 50/50 to Evaluate Efficacy and Safety in Type 2 Diabetic Patients With Inadequate Glycemic Control on Oral Therapy. (SIMPLE Study)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Lispro Mix 50/50


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed as having type 2 Diabetes. Patients who have not been on insulin treatment within 6 months. Patients who have been taking OADs for at least 90 days. Patients with an HbA1c level in the range of 7.5% to 11.0%. Patients with a Body-Mass Index (BMI) of 35 kg/m² or below. Exclusion Criteria: Patients having pre-proliferative or proliferative retinopathy (except for old retinopathy with no need for treatment). Patients having or suspected of having malignancy Patients having serious complications of the heart, liver, or kidney. Patients hypersensitive or allergic to insulin or insulin analog preparations or a history of it. Patients receiving systemic steroids. Are currently enrolled in a clinical trial of a non-approved drug. Or patients who participated in other clinical trials including post-marketing clinical trials within 90 days prior to informed consent being obtained. Patients of child-bearing potential. Breastfeeding patients. Patients with a positive result in a pregnancy test performed for women of child-bearing potential.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lispro 50/50<br> | Drug: Lispro Mix 50/50<br>* Administered subcutaneously once daily for 16 weeks, twice daily for 16 weeks, and three times daily for 16 weeks dependent on glycemic control.<br>* Other names: Humalog Mix50;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 48 Endpoint | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 6.5% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 6.9%. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 6.5% at Week 16 and Week 32 Endpoints | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 6.5% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 6.9%. | Week 16 and Week 32 | 
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Below 7.0% at Week 16, 32 and 48 Endpoints | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The 7.0% HbA1c is the Japan Diabetes Society (JDS) value, and is equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c value of 7.4%. | Week 16 and Week 32 and Week 48 | 
| Percentage of Participants Achieving Hemoglobin A1c (HbA1c) Level Below 6.5% and Below 7.0% by Regimen at Week 48 Endpoint | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. 6.5% and 7.0% HbA1c are the Japan Diabetes Society (JDS) values, and are equivalent to the National Glycohemoglobin Standardization Program (NGSP) HbA1c values of 6.9% and 7.4%, respectively. | Week 48 | 
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 48 Endpoint | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. | Baseline, Week 48 | 
| Change From Baseline in Fasting Glucose at Week 48 Endpoint |  | Baseline, Week 48 | 
| Change From Baseline in Blood Glucose Profile at Week 48 Endpoint | Time course of changes in blood glucose was determined by 7-point self-monitoring of blood glucose (SMBG) during the day (before breakfast, lunch, and dinner, 2 hours after the start of each meal, and at bedtime). | Baseline, Week 48 | 
| Change From Baseline in Fasting C-Peptide at Week 48 to Endpoint | C-peptide is a protein that is produced in the body along with insulin. | Baseline, Week 48 | 
| Change From Baseline in Fasting Serum Lipids at Week 48 Endpoint |  | Baseline, Week 48 | 
| Change From Baseline in Body Weight at Week 48 Endpoint |  | Baseline, Week 48 | 
| Total Daily Dose of Insulin at Baseline, Week 16, Week 32 and Week 48 |  | Baseline and Weeks 16, 32 and 48 | 
| Percentage of Participants Developing Hypoglycemia at Any Time From Baseline Through Week 48 | Results are reported as the percentage of participants experiencing hypoglycemia, which was considered any hypoglycemic event in which participants themselves recognized hypoglycemia-related signs and symptoms, or they had a blood glucose level below 50 milligram/deciliter (mg/dL) regardless of signs, symptoms or the relationship to treatment. | Baseline through Week 48 | 
| Number of Hypoglycemia Episodes Participants Experienced at Any Time From Baseline Through Week 48 | A hypoglycemic episode was considered any hypoglycemic event in which participants themselves recognized hypoglycemia-related signs and symptoms, or participants had a blood glucose level below 50 mg/dL regardless of signs, symptoms or the relationship to treatment. | Baseline through Week 48 |