A Trial Investigating the Efficacy and Safety of Flexible vs. Fixed Dosing and Simple vs. Stepwise Titration With Once Daily (OD) Insulin Degludec in Inadequately Treated Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Trial Investigating the Efficacy and Safety of Flexible vs. Fixed Dosing and Simple vs. Stepwise Titration With Once Daily Insulin Degludec in Inadequately Treated Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01880736
• Other study ID #: NN1250-4060
• Secondary ID: U1111-1137-0953J
• Status: Completed
• Phase: Phase 3
• First received: June 14, 2013
• Last updated: February 18, 2016
• Start date: June 2013
• Est. completion date: April 2014

Study information

• Verified date: February 2016
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Asia. The aim of the trial is to investigate the efficacy and safety of flexible versus fixed dosing and simple versus stepwise titration with OD insulin degludec in inadequately treated subjects with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 458
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Current treatment with IGlar (insulin glargine) with or without OADs (oral antidiabetic drug). All antidiabetic treatments should have been on-going for at least 12 weeks prior to randomisation, and doses of OADs should have been stable in this period of time. - Please note that a maximum of 3 OADs are allowed during this trial: metformin, sulphonylurea (SU)/glinides, dipeptidyl peptidase 4 (DPP-IV) inhibitors, alfa-glucosidaseinhibitors or pioglitazone.

• Diagnosis of T2DM (type 2 diabetes mellitus) at the discretion of the investigator for at least 26 weeks prior to visit 1 (Screening visit)

• HbA1c 7.0-9.5% (both inclusive) by central laboratory analysis

• Body mass index (BMI) equal to or below 35 kg/m^2

Exclusion Criteria:

• Any chronic disorder or severe disease which, in the opinion of the Investigator might jeopardise subject's safety or compliance with the protocol

• Stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty; all within the last 26 weeks prior to Visit 1 (Screening visit)

• Impaired renal function, defined as serum-creatinine higher than or equal to 1.4 mg/dL for males and higher than or equal to 1.3 mg/dL for females

• Current or past (within the last 5 years) malignant neoplasms (except basal cell and squamous cell skin carcinoma)

• Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria in a period of 12 weeks prior to randomisation

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• insulin degludec
Individual dose adjusted once weekly. IDeg (100 U/mL, 3 mL FlexTouch® pen PDS290) to be administered under the skin OD with the option to vary time of administration within a window of plus/minus 8 hours. A maximum of 3 pre-trial OADs are allowed during the trial at an unchanged, stable dose level and dosing frequency.
• insulin degludec
Individual dose adjusted once weekly. IDeg (100 U/mL, 3 mL FlexTouch® pen PDS290) to be administered subcutaneously (under the skin) OD at the same time each day. A maximum of 3 pre-trial oral anti-diabetic drugs (OADs) are allowed during the trial at an unchanged, stable dose level and dosing frequency.
• insulin degludec
Individual dose adjusted once weekly. IDeg (100 U/mL, 3 mL FlexTouch® pen PDS290) to be administered under the skin OD, with the option to vary time of administration within a window of plus/minus 8 hours. A maximum of 3 pre-trial OADs are allowed during the trial at an unchanged, stable dose level and dosing frequency.
• insulin degludec
Individual dose adjusted once weekly. IDeg (100 U/mL, 3 mL FlexTouch® pen PDS290) to be administered under the skin OD at the same time each day. A maximum of 3 pre-trial OADs are allowed during the trial at an unchanged, stable dose level and dosing frequency.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c (%) Glycosylated Haemoglobin)	Changes from baseline in HbA1c values over time period of Week 0-26 were evaluated by dosing regimen (flexible vs. fixed dosing) and by titration algorithm (simple vs stepwise)	Week 0, week 26	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG)	Changes from baseline in FPG values over the time period of Week 0-26 were evaluated by dosing regimen (flexible vs. fixed dosing) and by titration algorithm (simple vs stepwise).	Week 0, week 26	No
Secondary	Responder for HbA1c (%) Based on Central Laboratory Assessment: HbA1c Below 7.0% at End of Trial	The number of subjects who achieved the pre-defined HbA1c target (<7.0%) after 26 weeks of treatment was recorded by dosing regimen (flexible vs. fixed dosing) and by titration algorithm (simple vs stepwise).	After 26 weeks of treatment	No
Secondary	Incidence of Treatment Emergent Adverse Events (TEAEs)	The incidences of treatment emergent adverse events (TEAEs) over the time period of Week 0-26 were recorded by dosing regimen (flexible vs. fixed dosing); and by titration algorithm (simple vs stepwise).	Weeks 0-26	No
Secondary	Number of Treatment Emergent Confirmed Hypoglycaemic Episodes (Defined as Severe Hypoglycaemia and/or a Measured Plasma Glucose (PG) Less Than 3.1 mmol/L (Less Than 56 mg/dL))	The confirmed hypoglycaemic episodes (defined as severe hypoglycaemia and/or a measured plasma glucose (PG) less than 3.1 mmol/L [less than 56 mg/dL]) over the time period of Week 0-26 was recorded by dosing regimen (flexible vs. fixed dosing); and by titration algorithm (simple vs stepwise).	Weeks 0-26	No
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA) Definition	Number of treatment emergent hypoglycaemic episodes according to the ADA definition (classified as severe hypoglycaemia, documented hypoglycaemia, asymptomatic hypoglycaemia, probable symptomatic hypoglycaemia, relative hypoglycaemia) over the time period of Week 0-26 was recorded by dosing regimen (flexible vs. fixed dosing) and by titration algorithm (simple vs stepwise).	Weeks 0-26	No
Secondary	Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period	The number of treatment mergent confirmed hypoglycaemic episodes in the maintenance period from Week 16 to end of trial (week 27) was recorded by dosing regimen (flexible vs. fixed dosing) and by titration algorithm (simple vs. stepwise). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed plasma glucose value of less than 3.1 mmol/L.	From Week 16 to end of trial (week 27)	No
Secondary	Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes	The number of treatment emergent nocturnal (00:01-05:59 am) confirmed hypoglycaemic episodes over the time period of Week 0-26 was recorded by dosing regimen (flexible vs. fixed dosing) and by titration algorithm (simple vs stepwise). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed plasma glucose value of less than 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.	Weeks 0-26	No
Secondary	Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes in the Maintenance Period	The number of treatment emergent nocturnal (00:01-05:59 am) confirmed hypoglycaemic episodes in the maintenance period from 16 weeks to end of trial (week 27) was recorded by dosing regimen (flexible vs. fixed dosing); and by titration algorithm (simple vs stepwise). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed plasma glucose value of less than 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.	From week 16 to end of trial (week 27)	No

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