Comparison of Biphasic Insulin Aspart 30 Individually Adjusted by the Subject and the Trial Physician, Both Combined With Metformin in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial was conducted in Asia, Europe and South America. The aim of this trial was to confirm efficacy of subject driven titration (individually adjusted) of biphasic insulin aspart 30 (BIAsp 30) twice daily in terms of glycaemic control assessed by change in glycosylated haemoglobin (HbA1c).

Official Title
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A 20 Week Randomised, Multinational, Open Labelled, 2 Armed, Parallel Group Comparison of Twice Daily Subject Driven Titration of Biphasic Insulin Aspart (BIAsp) 30 Versus Twice Daily Investigator-driven Titration of Biphasic Insulin Aspart (BIAsp) 30 Both in Combination With Metformin in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin Analogues

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: biphasic insulin aspart 30


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes for a minimum of 12 months prior to Visit 1 (screening) Currently treated with a basal insulin analogue for at least 3 months prior to Visit 1 (screening) Stable treatment (no change in dose or regimen) with a total daily dose of at least 1500 mg metformin or maximum tolerated dose (minimum 1000 mg) ± additional OAD treatment. The metformin treatment must have been stable for at least 2 months prior to Visit 1 (screening) HbA1c higher or equal to 7.0% and below or equal to 10.0% (one re-test within one week of screening visit was allowed. The last sample was to be conclusive) Body Mass Index (BMI) below or equal to 40.0 kg/m^2 Able and willing to eat at least 2 main meals each day during the trial Able and willing to adhere to the protocol including compliance with performance of self measured plasma glucose (SMPG), injection regimen and titrating themselves according to the protocol Experience in performing self measured plasma glucose (SMPG) Exclusion Criteria: Treatment with any thiazolidinedione (TZD) and glucagon-like peptide-1 (GLP-1) receptor agonists or pramlintide within the last 3 months prior to Visit 1 (screening) Impaired hepatic function defined as alanine aminotransferase (ALAT) above or equal to 2.5 times upper referenced limit (one re-test within one week of screening visit was allowed. The last sample was to be conclusive) Impaired kidney function with serum creatinine above or equal to 133 micromol/L (1.5 mg/dL) for males and above or equal to 124 micromol/L (1.4 mg/dL) for females (one re-test within one week of screening visit was allowed. The last sample was to be conclusive) Cardiac problems or uncontrolled treated/untreated severe hypertension (defined as systolic blood pressure higher or equal to 180 mmHg and/or diastolic blood pressure higher or equal to 100 mmHg) Previous use of pre-mixed insulin products (pre-mixed insulin analogues or pre-mixed human preparations) or bolus insulin. Previous use of pre-mixed or bolus insulin products was allowed only in case of hospitalisation or a severe condition requiring intermittent use of pre-mixed or bolus insulin products for less than 14 consecutive days, but not during the last 3 months prior to screening visit (Visit 1)

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: Subject-driven titration BIAsp 30 (BID) + metformin<br>The subjects performed the titration of BIAsp 30 dose. | Drug: biphasic insulin aspart 30<br>* Administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued.<br>|
| Active Comparator: Investigator-driven titration BIAsp 30 (BID) + metformin<br>The investigator performed the titration of BIAsp 30 dose. | Drug: biphasic insulin aspart 30<br>* Administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Glycosylated Haemoglobin) - FAS | Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in full analysis set (FAS). | Week 0, week 20 | 
| Change in HbA1c (Glycosylated Haemoglobin) - PP | Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in per protocol (PP) analysis set. | Week 0, week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) (Central Laboratory Values) | Estimated mean change from baseline in FPG after 20 Weeks of treatment | Week 0, week 20 | 
| Number of Treatment Emergent Hypoglycaemic Episodes | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of trial product, and no later than one day after product administration. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. | Week 0 to week 20 | 
| Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score | From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state. | Week 0 | 
| Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score | From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state. | Week 4 | 
| Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score | From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state. | Week 20 |