Comparing Efficacy and Safety of Insulin Detemir Plus Insulin Aspart and NPH Insulin Plus Human Soluble Insulin With or Without Metformin in Chinese Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia. The aim of this trial is to compare efficacy and safety of insulin detemir plus insulin aspart and NPH insulin plus human soluble insulin both in a basal bolus regimen with or without metformin in Chinese patients with type 2 diabetes. The trial adopts a group sequential design, where the analysis of the primary efficacy endpoint will be performed at the interim analysis, in addition to the final formal analysis. The decision to continue or stop the trial will be based on the result of the interim analysis.

Official Title
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A 2-week, Randomised, Controlled, Open-label, Two-group Parallel, Multi-centre Trial Comparing Efficacy and Safety of Insulin Detemir Plus Insulin Aspart and NPH Insulin Plus Human Soluble Insulin Both in a Basal Bolus Regimen With or Without Metformin in Chinese Inpatients With Type 2 Diabetes Currently Treated With Insulin Qualifying for Intensified Treatment

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: insulin detemir
* Drug: insulin aspart
* Drug: insulin NPH
* Drug: human soluble insulin
* Drug: metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus (diagnosed clinically) for at 12 months or longer Currently treated with basal insulin once daily or premixed insulin twice daily for at least 3 months with or without OAD(s), and total daily insulin dose less than 1.4 IU (U)/kg (If treated with metformin, unchanged total daily dose of at least 1000 mg for at least 3 months) Body Mass Index (BMI) equal to 40 kg/m^2 or below HbA1c (glycosylated haemoglobin A1c) between 7.0% and 10.0% by central laboratory analysis Plan to be admitted for optimising glycaemic control at least 2 days prior to the randomisation Exclusion Criteria: Treatment with thiazolidinediones (TZD) or Glucagon-Like Peptide-1 (GLP-1) receptor agonists within the last 3 months prior to the screening Anticipated change after the randomisation in concomitant medication known to interfere with glucose metabolism, such as systemic corticosteroids, beta-blockers and mono amine oxidase (MAO) inhibitors Previous participation in this trial (participation is defined as randomised. Re-screening of screening failures is allowed only once within the limits of the recruitment period.)

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: Insulin detemir / IAsp<br> | Drug: insulin detemir<br>* Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) once daily using NovoPen®4<br>Drug: insulin aspart<br>* Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) three times a day before a meal using NovoPen®4<br>Drug: metformin<br>* For subjects previously treated with metformin, the dosage and frequency will be kept unchanged<br>|
| Active Comparator: insulin NPH<br> | Drug: insulin NPH<br>* Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) once daily using NovoPen®4<br>Drug: human soluble insulin<br>* Dose individually adjusted. Administered subcutaneously/s.c. (under the skin) three times a day before a meal using NovoPen®4<br>Drug: metformin<br>* For subjects previously treated with metformin, the dosage and frequency will be kept unchanged<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean 8-point Plasma Glucose (PG) After Two Weeks of Treatment | Mean value of 8-point PG was the arithmetic mean of all 8 time-instant PG values of the 8-point PG profile. | Week 0, week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) After Two Weeks of Treatment | The FPG referred to pre-breakfast plasma glucose. | Week 0, week 2 | 
| Change From Baseline in Mean 2-hour Post Prandial Plasma Glucose (2hPPG) of 3 Meals After Two Weeks of Treatment | The mean 2hPPG was derived from the 8-point PG profile as the mean value of the available 120 minutes after each meal. | Week 0, week 2 | 
| Change From Baseline in Mean Value of Pre-lunch, Pre-dinner and Bedtime PG After Two Weeks of Treatment | The mean value of pre-lunch, pre-dinner and bedtime PG was derived from the 8-point PG profile measured before lunch, dinner and bedtime. | Week 0, week 2 | 
| Percentage of Subjects Achieving FPG < 6.0 mmol / L After Two Weeks of Treatment |  | Week 2 | 
| Percentage of Subjects Achieving Mean 2hPPG of 3 Meals < 8.0 mmol / L After Two Weeks of Treatment |  | Week 2 | 
| Percentage of Subjects Achieving Both FPG and 2hPPG Targets After Two Weeks of Treatment | FPG target was < 6.0 mmol / L, 2hPPG target was < 8.0 mmol / L. | Week 2 | 
| Percentage of Subjects Achieving FPG Target Without Nocturnal Hypoglycaemia After Two Weeks of Treatment | FPG target was < 6.0 mmol / L. Nocturnal hypoglycaemia was defined as a hypoglycaemic episode happened between 00:01 and 05:59 a.m. (both included). | Week 2 | 
| Change From Baseline in Fructosamine After Two Weeks of Treatment |  | Week 0, week 2 | 
| Incidence of Hypoglycaemic Episodes | All events summarized were treatment emergent hypoglycaemic events. Hypoglycaemic episodes were summarized based on the ADA classification and also according to an additional definition. Severe hypoglycemia: ADA definition. Minor hypoglycaemic episode: an episode with symptoms with confirmation by plasma glucose (PG) < 3.1 mmol/l (56 mg/dl) and was handled by the subject himself/herself, or any asymptomatic PG value < 3.1 mmol/l (56 mg/dl). A hypoglycaemia episode was defined as nocturnal if the time of onset was between 00:01 and 05:59 a.m. (both included), otherwise it was diurnal. | Weeks 0-2 |