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 (EasyMix)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: biphasic insulin aspart 30; Drug: metformin; Drug: glimepiride; Drug: insulin glargine

• Study Type: Interventional
• Enrollment (Actual): 521
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shenyang, China, 110001
    • Novo Nordisk Investigational Site
  • Tianjin, China, 300211
    • Novo Nordisk Investigational Site
  • Beijing
    • Beijing, Beijing, China, 100029
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 100853
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 100700
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 100101
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 100191
      • Novo Nordisk Investigational Site
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Novo Nordisk Investigational Site
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Novo Nordisk Investigational Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novo Nordisk Investigational Site
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Novo Nordisk Investigational Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210012
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 210029
      • Novo Nordisk Investigational Site
    • Wuxi, Jiangsu, China, 214023
      • Novo Nordisk Investigational Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Novo Nordisk Investigational Site
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • Novo Nordisk Investigational Site
    • Shenyang, Liaoning, China, 110021
      • Novo Nordisk Investigational Site
    • Shenyang, Liaoning, China, 110004
      • Novo Nordisk Investigational Site
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Novo Nordisk Investigational Site
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Novo Nordisk Investigational Site
    • Tianjin, Tianjin, China, 300070
      • Novo Nordisk Investigational Site
• Japan
  • Asahikawa-shi, Hokkaido, Japan, 078 8510
    • Novo Nordisk Investigational Site
  • Chuo-ku, Tokyo, Japan, 103 0002
    • Novo Nordisk Investigational Site
  • Gifu city, Gifu, Japan, 5008717
    • Novo Nordisk Investigational Site
  • Higashi-ku, Japan, 812 8582
    • Novo Nordisk Investigational Site
  • Kumamoto-shi,Kumamoto, Japan, 862 0976
    • Novo Nordisk Investigational Site
  • Minato-ku, Japan, 108 0073
    • Novo Nordisk Investigational Site
  • Osaka-shi, Japan, 5300025
    • Novo Nordisk Investigational Site
  • Osaka-shi, Osaka, Japan, 545 8586
    • Novo Nordisk Investigational Site
  • Shimotsuka-gun, Japan, 321 0293
    • Novo Nordisk Investigational Site
  • Shimotsuke-shi, Tochigi, Japan, 329 0433
    • Novo Nordisk Investigational Site
  • Shizuoka-shi, Japan, 424 0853
    • Novo Nordisk Investigational Site
  • Tagajo-shi, Japan, 985 0852
    • Novo Nordisk Investigational Site
  • Yokohama-shi, Japan, 235 0045
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIAsp 30; 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; Treat-to-target titration according to titration algorithm. Subcutaneous (under the skin) injection once daily.; Drug: metformin; China: Tablets, 500 mg. Min. 1500 mg/day. Japan: Tablets, 250 mg. Min 500 mg/day.; Drug: glimepiride; China: Tablets, 2 mg. Min. 4 mg/day. Japan: Tablets, 1 mg. Min. 4 mg/day.
Active Comparator: Insulin glargine; 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; China: Tablets, 500 mg. Min. 1500 mg/day. Japan: Tablets, 250 mg. Min 500 mg/day.; Drug: glimepiride; China: Tablets, 2 mg. Min. 4 mg/day. Japan: Tablets, 1 mg. Min. 4 mg/day.; Drug: insulin glargine; Treat-to-target titration according to titration algorithm. Subcutaneous (under the skin) injection once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Yang W, Xu X, Liu X, Yang G, Seino Y, Andersen H, Jinnouchi H. Treat-to-target comparison between once daily biphasic insulin aspart 30 and insulin glargine in Chinese and Japanese insulin-naive subjects with type 2 diabetes. Curr Med Res Opin. 2013 Dec;29(12):1599-608. doi: 10.1185/03007995.2013.838155. Epub 2013 Sep 23.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: May 13, 2010
• First Submitted That Met QC Criteria: May 13, 2010
• First Posted (Estimate): May 14, 2010

Study Record Updates

• Last Update Posted (Actual): February 24, 2017
• Last Update Submitted That Met QC Criteria: January 10, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Insulin; Insulin, Globin Zinc; Insulin Aspart; Metformin; Insulin Glargine; Glimepiride; Biphasic Insulins; Insulin aspart, insulin aspart protamine drug combination 30:70
• Other Study ID Numbers: BIASP-3756; U1111-1114-4112 (Other Identifier: WHO); JapicCTI-101139 (Other Identifier: JAPIC)