Comparison of the Blood Sugar Lowering Effect of Biphasic Insulin Aspart 30 and Insulin Glargine Both Combined With Metformin and Glimepiride in Chinese and Japanese Subjects With Type 2 Diabetes New to Insulin Treatment

Study Overview
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Brief Summary
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This trial is conducted in Asia. The aim of this clinical trial is to investigate the blood sugar lowering effect of biphasic insulin aspart 30 once daily compared to insulin glargine once daily both in combination with metformin and glimepiride in Chinese and Japanese subjects with type 2 diabetes who have never received insulin before. The trial is conducted as a phase 4 trial in China and phase 3 in Japan.

Official Title
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An Open-labelled, Randomised, Parallel Group, 3 Week run-in and 24 Week Treat-to-target Comparison of Biphasic Insulin Aspart 30 Once Daily Versus Insulin Glargine Once Daily Both in Combination With Metformin and Glimepiride in Chinese and Japanese Insulin Naive Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: biphasic insulin aspart 30
* Drug: metformin
* Drug: glimepiride
* Drug: insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes treated with a maximum of three different types of oral anti-diabetic drugs (OADs) (including traditional Chinese medicine which contains active ingredients of known OADs) for more than 6 months Unchanged total daily dose of at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) metformin for the last two months Unchanged total daily dose of at least half maximum recommended total daily dose of any insulin secretagogue for the last two months Insulin naive HbA1c between 7.0% and 10.0% FPG (fasting plasma glucose) equal to or above 6.1 mmol/L (110mg/dL) Body Mass Index (BMI) below 40.0 kg/m^2 Exclusion Criteria: Treatment with any thiazolidinedione (TZD) and GLP-1 (glucagon like peptide-1) receptor antagonists during the last 3 months before Visit 1 in this trial Any disease or condition which the Investigator feels would interfere with the trial Any contraindication to metformin or glimepiride (according to local labelling)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 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: BIAsp 30<br>0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride | Drug: biphasic insulin aspart 30<br>* Treat-to-target titration according to titration algorithm. Subcutaneous (under the skin) injection once daily.<br>Drug: metformin<br>* China: Tablets, 500 mg. Min. 1500 mg/day. Japan: Tablets, 250 mg. Min 500 mg/day.<br>Drug: glimepiride<br>* China: Tablets, 2 mg. Min. 4 mg/day. Japan: Tablets, 1 mg. Min. 4 mg/day.<br>|
| Active Comparator: Insulin glargine<br>0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride | Drug: metformin<br>* China: Tablets, 500 mg. Min. 1500 mg/day. Japan: Tablets, 250 mg. Min 500 mg/day.<br>Drug: glimepiride<br>* China: Tablets, 2 mg. Min. 4 mg/day. Japan: Tablets, 1 mg. Min. 4 mg/day.<br>Drug: insulin glargine<br>* Treat-to-target titration according to titration algorithm. Subcutaneous (under the skin) injection once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) |  | Week 0, week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 9-point Plasma Glucose Profiles | Glycaemic control measured by 9-point plasma glucose (SPMG) profiles. The 9 timepoints for self-measurement during the day were: before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, before bedtime, at 2-4 a.m. and before breakfast the following day. | Week 24 | 
| Percentage of Subjects Achieving HbA1c Below 7.0% | The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment | Week 24 | 
| Percentage of Subjects Achieving HbA1c Below or Equal to 6.5% | The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment | Week 24 | 
| Number of Hypoglycaemic Episodes - All |  | Weeks 0-24 | 
| Number of Hypoglycaemic Episodes - Severe and Minor | Hypoglycaemic episodes (hypos) summarised based on American Diabetes Association classification (severe, documented symptomatic, asymptomatic, probable symptomatic, and relative hypoglycaemia) and according to additional definition (minor hypoglycaemia). Severe hypos: requiring another person to actively administer resuscitative actions. Minor hypos: symptoms with plasma glucose below 3.1 mmol/L (56 mg/dl), or any asympomatic plasma glucose below 3.1 mmol/L. | Weeks 0-24 | 
| Number of Hypoglycaemic Episodes | All episodes classified into nocturnal (time of onset between 00:00 (included) and 05:59 (included)). | Weeks 0-24 |