Investigating Efficacy and Safety of Biphasic Insulin Aspart 50 Twice Daily Versus Biphasic Human Insulin 50 Twice Daily Both in Combination With Metformin in Chinese Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This trial is conducted in Asia. The aim of the trial is to investigate the efficacy and safety of biphasic insulin aspart 50 (BIAsp 50) twice daily versus biphasic human insulin 50 (BHI 50) twice daily, both in combination with metformin, in Chinese subjects with type 2 diabetes mellitus.

Official Title
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A Multi-centre, Randomised, Open-labelled, 2-sequence, 2-period Crossover Trial to Investigate the Efficacy and Safety of Biphasic Insulin Aspart 50 (BIAsp 50) Twice Daily Versus Biphasic Human Insulin 50 (BHI 50) Twice Daily Both in Combination With Metformin in Chinese Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: biphasic insulin aspart 50
* Drug: biphasic human insulin 50


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus (diagnosed clinically) for at least 12 months Currently treated with premixed human insulin 50 BID for at least 3 months prior to screening visit (Visit 1) Currently treated with unchanged total daily dose of at least 1500 mg metformin or maximum tolerated dose at least 1000 mg/day metformin for at least 2 months prior to screening visit Glycosylated haemoglobin (HbA1c) 7.0% and 9.0% (both inclusive) (central laboratory) Exclusion Criteria: Treatment with any insulin secretagogue, alfa-glucosidase inhibitors, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP-4) inhibitors and Glucagon-like peptide-1 (GLP-1) receptor agonists within the last 3 months prior to screening Previous use of any insulin other than premixed human insulin 50 BID within 3 months prior to Visit 1 Previous use of insulin intensification treatment (premixed insulin thrice daily, basal bolus regimen, and continuous subcutaneous insulin infusion (CSII)) for more than 14 days

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1 (Group A)<br>Group A will receive BIAsp 50 BID during the first 4 weeks (treatment period 1) then switch to BHI 50 BID for further 4 weeks (treatment period 2) | Drug: biphasic insulin aspart 50<br>* Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.<br>Drug: biphasic human insulin 50<br>* Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.<br>|
| Experimental: Treatment sequence 2 (Group B)<br>Group B will receive BHI 50 BID during the first 4 weeks (treatment period 1), then switch to BIAsp 50 BID for further 4 weeks (treatment period 2) | Drug: biphasic insulin aspart 50<br>* Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.<br>Drug: biphasic human insulin 50<br>* Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-hour PPG (Postprandial Plasma Glucose) Increment Following a Standard Meal Test | The 2-hour PPG increment is the difference between the plasma glucose (PG) value at 120 minutes after standard meal test and the fasting PG value. | After 4 weeks of treatment in each treatment sequence | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -1-hour PPG Increment Following a Standard Meal Test | The 1-h PPG increment is the difference between the plasma glucose (PG) value at 60 minutes after standard meal test and the fasting PG value. | After 4 weeks of treatment in each treatment sequence | 
| -IAUC (Incremental Area Under the Curve) for PPG (0-2 Hours) Following a Standard Meal Test | AUC for plasma glucose was calculated by the trapezoidal method using 30-min sampling time points, and IAUC for PPG (0-2h) data was analyzed using a normal linear mixed model. | After 4 weeks of treatment in each treatment sequence | 
| 2-hour PPG Increments Over Each of the 3 Main Meals in 8-point SMPG (Self-measured Plasma Glucose) Profile | PPG increments over each of the 3 main meals were derived from the 8-point SMPG profile as the difference between PG values available 120 minutes after meal and before meal. | After 4 weeks of treatment in each treatment sequence | 
| The Mean 2-hour PPG Increments of the 3 Main Meals in 8-point SMPG Profile | Mean post prandial PG increment over all meals was derived as the mean of all available meal increments. | After 4 weeks of treatment in each treatment sequence | 
| Incidence of Hypoglycemic Episodes | Treatment Emergent Hypoglycemic Episode refers to those the onset of the episode is on or after the first day of exposure to randomized treatment and no later than the last day of randomized treatment. Results are presented by American Diabetes Association classification of hypoglycemia. | During 4 weeks of treatment in each treatment sequence | 
| Incidence of AEs (Adverse Event) | Treatment emergent AE (TEAE) is defined as an event that has onset date on or after the first day of exposure to randomized treatment and no later than the last day of randomized treatment. | During 4 weeks of treatment in each treatment sequence |