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)

• ClinicalTrials.gov Identifier: NCT01868542
• Recruitment Status: Completed
• First Posted: June 4, 2013
• Results First Posted: June 29, 2016
• Last Update Posted: March 3, 2017
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: insulin detemir	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: June 2013
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in Glycosylated Haemoglobin A1c (HbA1c) From Baseline. [ Time Frame: Week 0, week 20 ]
   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.

Secondary Outcome Measures :

1. Change in HbA1c [ Time Frame: Week 0, week 12 ]
   Change in HbA1c at 12 weeks of treatment from visit 2.
2. Proportion of Subjects Achieving HbA1c Below 7.0% [ Time Frame: Week 20 ]
   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.
3. Change in Fasting Plasma Glucose From Baseline [ Time Frame: week 0, week 12 ]
   Change in fasting plasma glucose from baseline.
4. Incidence of Hypoglycaemic Episodes : Nocturnal (23:00-05:59) and Over 24 Hours. [ Time Frame: For 20 weeks of treatment 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.
5. Change in Fasting Plasma Glucose From Baseline [ Time Frame: Week 0, week 20 ]
   Change in fasting plasma glucose from baseline.
6. Incidence of Adverse Events [ Time Frame: Week 20 ]
   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)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Korea, Republic of

Novo Nordisk Investigational Site

Daejeon, Korea, Republic of, 301-721

Novo Nordisk Investigational Site

Daejeon, Korea, Republic of, 301-723

Novo Nordisk Investigational Site

Daejeon, Korea, Republic of, 302-120

Novo Nordisk Investigational Site

Daejeon, Korea, Republic of, 302-718

Novo Nordisk Investigational Site

Daejeon, Korea, Republic of, 330-721

Novo Nordisk Investigational Site

Daejeon, Korea, Republic of, 361-711

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452); Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01868542
• Other Study ID Numbers: NN304-3994; U1111-1132-9267 ( Other Identifier: WHO )
• First Posted: June 4, 2013
• Results First Posted: June 29, 2016
• Last Update Posted: March 3, 2017
• Last Verified: January 2017

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Insulin Detemir; Hypoglycemic Agents; Physiological Effects of Drugs