A Study to Compare Insulin Intensification of Biphasic Insulin Aspart 30 and Insulin Analogues (Insulin Glargine and Insulin Aspart) in Insulin naïve Type 2 Diabetic Patients

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 32-week Randomised, Multinational, Treat-to-target, Open Label, Parallel Group Comparison of Stepwise Insulin Intensification of Biphasic Insulin Aspart (BIAsp) 30 and Basal-bolus Therapy With Insulin Glargine and Insulin Aspart in Insulin naïve Type 2 Diabetic Patients Inadequately Controlled on Oral Anti-diabetic Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02453685
• Other study ID #: BIASP-4157
• Secondary ID: 2014-003708-62U1
• Status: Completed
• Phase: Phase 4
• Start date: August 31, 2015
• Est. completion date: September 20, 2016

Study information

• Verified date: September 2018
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted globally. The aim of this trial is to compare stepwise insulin intensification of biphasic insulin aspart (BIAsp) 30 and basal-bolus therapy with insulin glargine and insulin aspart in insulin naïve type 2 diabetic patients inadequately controlled on oral anti-diabetic therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 335
• Est. completion date: September 20, 2016
• Est. primary completion date: September 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial

• Male or female, age at least 18 years at the time of signing informed consent

• Type 2 diabetes subjects clinically diagnosed at least 6 months prior to screening

• Treatment with stable daily dose (for at least 90 days prior to screening) of: - Metformin (equal or above 1000 mg or maximum tolerated dose documented in the patient medical record) and - Sulfonylurea - and willing to discontinue any other oral antidiabetic drugs containing insulin secretagogues, DPP4i (dipeptidyl peptidase-4 inhibitor), SGLT2 (sodium glucose co-transporter 2), colesevelam, bromocriptin and/or combination products at randomisation

• Insulin-naïve. Short term insulin treatment for acute illnesses for a total of 14 days or less is allowed as is prior insulin treatment for gestational diabetes

• HbA1c (glycosylated haemoglobin) 7.0-9.5 % (both inclusive) analysed by central laboratory

• Willing to consume 3 main meals daily (morning, mid-day and evening) throughout the entire trial. The definition for 'main meal' will be according to the investigator's discretion

Exclusion Criteria:

• Anticipated initiation or change in concomitant medications known to affect weight or glucose metabolism, in excess of 14 days (i.e. sibutramine, orlistat, thyroid hormones, systemic corticosteroids and other weight loss/modifying agents)

• Impaired liver function, defined as ALT (alanine aminotransferase) at least 2.5 times upper limit of normal (central laboratory value measured at screening visit)

• Inadequately treated high blood pressure defined as Class 2 hypertension or higher (i.e. systolic blood pressure equal to or above 160 mm Hg or diastolic equal to or above 100 mm Hg) in accordance with the National High Blood Pressure Education Program, 7th Joint National Committee1 and ESH/ESC 2013 Guidelines2

• Within the past 180 days prior to randomisation, any of the following: Myocardial Infarction, stroke or hospitalization for unstable angina and /or transient ischemic attack

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• biphasic insulin aspart 30
Injected s.c./subcutaneously once daily with the largest meal Subjects should continue their pre-trial metformin and sulfonylurea dosages all throughout the trial while other oral antidiabetic drugs will be discontinued.
• insulin glargine
Injected s.c./subcutaneously once daily at the same time every day, with the possibility of treatment intensification with insulin aspart (Basal-bolus arm) Subjects should continue their pre-trial metformin and sulfonylurea dosages all throughout the trial while other oral antidiabetic drugs will be discontinued.
• insulin aspart
Injected s.c./subcutaneously once daily.

Locations

Country	Name	City	State
Australia	Novo Nordisk Investigational Site	Broadmeadow	New South Wales
Australia	Novo Nordisk Investigational Site	Coffs Harbour	New South Wales
Australia	Novo Nordisk Investigational Site	Fitzroy	Victoria
Australia	Novo Nordisk Investigational Site	Ipswich	Queensland
Australia	Novo Nordisk Investigational Site	Melbourne	Victoria
Bulgaria	Novo Nordisk Investigational Site	Petrich
Bulgaria	Novo Nordisk Investigational Site	Sliven
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Nyíregyhaza
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Madurai	Tamil Nadu
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Delhi
India	Novo Nordisk Investigational Site	Vellore	Tamil Nadu
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Nis
Thailand	Novo Nordisk Investigational Site	Bangkok
Thailand	Novo Nordisk Investigational Site	Bangkok
Thailand	Novo Nordisk Investigational Site	Bangkoknoi, Bangkok
Thailand	Novo Nordisk Investigational Site	Khon Kaen
Turkey	Novo Nordisk Investigational Site	Antalya
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Malatya
Turkey	Novo Nordisk Investigational Site	Rize
United Arab Emirates	Novo Nordisk Investigational Site	Ajman
United Arab Emirates	Novo Nordisk Investigational Site	Dubai
United Arab Emirates	Novo Nordisk Investigational Site	Ras Al Khaimah
United Arab Emirates	Novo Nordisk Investigational Site	Umm Al Quwain

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Australia,  Bulgaria,  Hungary,  India,  Korea, Republic of,  Serbia,  Thailand,  Turkey,  United Arab Emirates, 

References & Publications (1)

Linjawi S, Lee BW, Tabak Ö, Lövdahl S, Werther S, Abusnana S. A 32-Week Randomized Comparison of Stepwise Insulin Intensification of Biphasic Insulin Aspart (BIAsp 30) Versus Basal-Bolus Therapy in Insulin-Naïve Patients with Type 2 Diabetes. Diabetes The — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (Glycosylated Haemoglobin)	Change in HbA1c from baseline (week 0) to week 32.	Week 0, week 32
Secondary	HbA1c Below 7.0% Without Severe Hypoglycaemic Episodes	Percentage of subjects with HbA1c below 7.0% after 32 weeks of randomised treatment without treatment emergent severe hypoglycaemic episodes during the last 12 weeks of treatment. Subjects withdrawn before 32 weeks were handled as non-responders. Severe hypoglycaemic episode was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration.	After 32 weeks of treatment (yes/no)
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes Classified According to the American Diabetes Association (ADA) and the Novo Nordisk Definitions	Hypoglycaemic episodes were classified as severe, Asymptomatic, Documented symptomatic, Pseudo, and Probable symptomatic as per ADA classification. As symptoms of hypoglycaemia occur below a PG level of 3.1 mmol/L, (56 mg/dL) Novo Nordisk classification included hypoglycaemia with plasma glucose (PG) levels below 3.1 mmol/L (56 mg/dL) in the definition of blood glucose confirmed hypoglycaemia. Hence, Novo Nordisk classification included following types of hypoglycaemia in addition to ADA classification: Severe hypoglycaemia, Symptomatic blood glucose confirmed hypoglycaemia, Asymptomatic blood glucose confirmed hypoglycaemia, Severe or blood glucose confirmed symptomatic hypoglycaemia, Blood glucose confirmed hypoglycaemia, and Severe or blood glucose confirmed hypoglycaemia. Reported data represents total of all hypoglycaemic episodes.	Weeks 0-32
Secondary	Total Daily Insulin Dose	Total daily insulin dose in the basal bolus treatment group and in BIAsp 30 treatment group at each week of each treatment.	Weeks 0-32

External Links

•   Clinical Trials at Novo Nordisk