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)

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

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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: insulin detemir

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daejeon, Korea, Republic of, 302-120
    • Novo Nordisk Investigational Site
  • Daejeon, Korea, Republic of, 361-711
    • Novo Nordisk Investigational Site
  • Daejeon, Korea, Republic of, 330-721
    • Novo Nordisk Investigational Site
  • Daejeon, Korea, Republic of, 302-718
    • Novo Nordisk Investigational Site
  • Daejeon, Korea, Republic of, 301-721
    • Novo Nordisk Investigational Site
  • Daejeon, Korea, Republic of, 301-723
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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

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: 3-0-3 Algorithm; 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; Insulin detemir was administered once daily to the subjects. The dose was titrated based on the previous breakfast SMPG values.
Experimental: 2-4-6-8 Algorithm; 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; Insulin detemir was administered once daily to the subjects. The dose was titrated based on the previous breakfast SMPG values.

What is the study measuring?

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

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, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: May 30, 2013
• First Submitted That Met QC Criteria: May 30, 2013
• First Posted (Estimate): June 4, 2013

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: January 18, 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; Insulin Detemir
• Other Study ID Numbers: NN304-3994; U1111-1132-9267 (Other Identifier: WHO)