A Trial Comparing the Glycaemic Control of Levemir® Administered Once Daily According to Two Insulin Detemir Titration Algorithms After 20 Weeks in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Treatment With or Without Other Anti-diabetic Drugs (OADs)

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 compare the glycaemic control of Levemir® (insulin detemir) administered once daily according to two titration algorithms after 20 weeks in subjects with type 2 diabetes inadequately controlled on metformin treatment with or without other anti-diabetic drugs (OADs).

Official Title
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A 20-week, Randomised, Multi-centre, Open-labelled Trial Comparing the Glycaemic Control of Levemir® Administered Once Daily According to Two Titration Algorithms (3-0-3 Algorithm and 2-4-6-8 Algorithm) After 20 Weeks in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Treatment in Korea

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: insulin detemir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Diagnosed with type 2 diabetes mellitus at least 3 months prior to Visit 1 (week -2) - Treatment with at least 1000 mg metformin per day with/without other OADs at a stable dose (at either the maximal tolerated dose or at least half of the maximum recommended dose according to the package insert) for at least 3 months prior to Visit 1 - Insulin-naïve subjects - HbA1c above or equal to 7.5% by central laboratory analysis - Body mass index (BMI) below or equal to 35.0 kg/m^2 Exclusion Criteria: - Female who is breast-feeding - The receipt of any investigational product within 4 weeks prior to Visit 1 - Any contraindication to insulin detemir according to the domestic labelling - Anticipated change of dose of any systemic treatment with products, which in the investigator's opinion could interfere with glucose metabolism (such as systemic corticosteroids, beta-blockers, monoamine oxidase [MAO] inhibitors) - Clinically significant diseases which, in the investigator's opinion, may confound the results of the trial or pose additional risk in administering trial product - Any conditions that the investigator judges would interfere with trial participation or evaluation of the results

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: 3-0-3 Algorithm<br>A once daily dosage of Insulin detemir (Levemir®) 100 U/mL 3 mL FlexPen® for subcutaneous administration was selected for this trial.During the treatment period insulin detemir was adjusted by the subject themselves (self-titration). Self-titration was performed every 3 days based on the lowest of three previous consecutive pre-breakfast SMPG values.Based on this glucose value, self-adjustment of insulin detemir dose was done. Metformin and Sulfonlylurea were allowed as OADs. For SMPG values, the following insulin detemir dose adjustments were done : >6.1 mmol/L (>110 mg/dL) +3U insulin detemir, 4.4-6.1 mmol/L (80-100 mg/dL) No adjustment in insulin detemir, < 4.4 mmol/L (<80 mg/dL) -3U insulin detemir. | Drug: insulin detemir<br>* Insulin detemir was administered once daily to the subjects. The dose was titrated based on the previous breakfast SMPG values.<br>|
| Experimental: 2-4-6-8 Algorithm<br>A once daily dosage of Insulin detemir (Levemir®) 100 U/mL 3 mL FlexPen® for subcutaneous administration was selected for this trial. During the treatment period insulin detemir was adjusted by the subject themselves (self-titration). Self-titration was performed every 3 days based on the lowest of three previous consecutive pre-breakfast SMPG values.Based on this glucose value, self-adjustment of insulin detemir dose was done. Metformin and Sulfonlylurea were allowed as OADs. For SMPG values , the following insulin detemir dose adjustments were done : >10.0 mmol/L (180 mg/dL) +8U insulin detemir, 9.1-10.0 mmol/L (163-180 mg/dL) +6U insulin detemir, 8.1-9.0 mmol/L (145-162 mg/dL) +4 U insulin detemir, 7.1-8.0 mmol/L (127-144 mg/dL) +2U insulin detemir, 6.1-7.0 mmol/L (109-126 mg/dL) +2U insulin detemir, 4.1-6.0 mmol/L (73-108 mg/dL) No adjustment in insulin detemir, 3.1-4.0 mmol/L (56-72 mg/dL) -2U insulin detemir, <3.1 mmol/L (<56 mg/dL) -4U insulin detemir. | Drug: insulin detemir<br>* Insulin detemir was administered once daily to the subjects. The dose was titrated based on the previous breakfast SMPG values.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin A1c (HbA1c) From Baseline. | Change in glycosylated haemoglobin A1c (HbA1c) (%) from baseline after 20 weeks of treatment. Only the subjects in the full analysis set with HbA1c values after 20 weeks of treatment were included. | Week 0, week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change in HbA1c at 12 weeks of treatment from visit 2. | Week 0, week 12 | 
| Proportion of Subjects Achieving HbA1c Below 7.0% | Responder was a dichotomous endpoint (responder/non-responder) that was defined based on whether a subject had met the ADA HbA1c target at end of trial (HbA1c < 7.0% at end of trial) during 20 weeks of treatment. | Week 20 | 
| Change in Fasting Plasma Glucose From Baseline | Change in fasting plasma glucose from baseline. | week 0, week 12 | 
| Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours. | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred after the first administration of the investigational medicinal product (IMP), and no later than the last day on trial product. Hypoglycaemic episodes were defined as nocturnal if the time of onset was between 23:00 and 05:59 inclusive. All plasma glucose values: · equal or below 3.9 mmol/L (70 mg/dL) or · higher than 3.9 mmol/L (70 mg/dL) when they occur in conjunction with hypoglycaemic symptoms. | For 20 weeks of treatment and over 24 hours | 
| Change in Fasting Plasma Glucose From Baseline | Change in fasting plasma glucose from baseline. | Week 0, week 20 | 
| Incidence of Adverse Events | A treatment emergent adverse event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than the day of visit 22.(week 20) | Week 20 |