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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: biphasic insulin aspart 50; Drug: biphasic human insulin 50

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment sequence 1 (Group A); 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; Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.; Drug: biphasic human insulin 50; Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.
Experimental: Treatment sequence 2 (Group B); 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; Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.; Drug: biphasic human insulin 50; Administered subcutaneously (s.c., under the skin) twice daily (BID). Dose individually adjusted. All subjects will receive metformin in combination with trial insulin.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: June 28, 2013
• First Posted (Estimate): July 3, 2013

Study Record Updates

• Last Update Posted (Estimate): July 9, 2015
• Last Update Submitted That Met QC Criteria: June 16, 2015
• Last Verified: June 1, 2015

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; Insulin; Insulin, Globin Zinc; Insulin Aspart; Biphasic Insulins
• Other Study ID Numbers: BIASP-4058; U1111-1137-2342 (Other Identifier: WHO)