Efficacy and Safety of Basal-bolus Therapy, Comparing Stepwise Addition of Insulin Aspart Versus Complete Basal-bolus Regimen

Phase 4

Completed

Conditions: Diabetes Mellitus, Type 2
Diabetes

Interventions: Drug: insulin aspart
Drug: insulin detemir

Registration Number: NCT01165684

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Europe, and North and South America. The aim of this clinical trial is to investigate if the two treatments are equally effective.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 401

Inclusion Criteria

Type 2 diabetes (diagnosed clinically) for at least 12 months
Basal insulin treatment (NPH once or twice daily, insulin glargine once daily or insulin detemir once daily) for at least 6 months
HbA1c: 7.0-9.0 % (both inclusive) by central laboratory analysis (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive)
BMI (Body Mass Index) less than 40.0 kg/m^2

Exclusion Criteria

Previous use of pre-mix or bolus insulin (allowed is previous use of bolus insulin only in case of a hospitalisation or a severe condition requiring intermittent use of bolus insulin for less than 14 consecutive days, but not during the last 6 months prior to screening visit (Visit 1)
Use of GLP-1 (Glucagon-like peptide-1) receptor agonists or pramlintide within the last 6 months prior to prior to screening visit (Visit 1)
Anticipated change in concomitant medication known to interfere significantly with glucose metabolism (e.g. systemic corticosteroids, beta-blockers, MAO (Monoamine oxidase) inhibitors, etc.)
Cardiovascular disease, within the last 12 months prior to screening visit (Visit 1), defined as: 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
Uncontrolled treated/untreated severe hypertension (systolic blood pressure sitting at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg). For Argentina: systolic blood pressure sitting at least 150 mmHg and/or diastolic blood pressure at least 90 mmHg
Impaired liver function, defined as ALAT (Alanine aminotransferase) at least 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive)
Impaired renal function defined as serum creatinine above 135 micromol/L (above 1.5 mg/dL) for males and above 110 micromol/L (above 1.2 mg/dL) for females; and, if required by the locally applicable metformin label, glomerular filtration rate below 60 ml/min, calculated by the Cockroft & Gault formula). One retest within a week is permitted with the result of the last sample being conclusive
Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode, during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
Proliferative retinopathy or maculopathy requiring treatment according to the Investigator
Treatment with OADs (Oral anti-diabetic drug) contraindicated or unapproved for combination treatment with insulin (according to local OAD label)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Step-wise	insulin detemir	-
Step-wise	insulin aspart	-
Basal-bolus	insulin detemir	-
Basal-bolus	insulin aspart	-

Primary Outcome Measures

Name	Time	Method
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32	Week 0, Week 32	Estimated mean change from baseline in HbA1c after 32 Weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Fasting Plasma Glucose (FPG) at Week 21	Week 21	Mean FPG at Week 21
Body Mass Index (BMI) at Week 32	Week 32	Estimated mean BMI after 32 Weeks of treatment
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10	Week 0, Week 10	Estimated mean change from baseline in HbA1c after 10 Weeks of treatment
Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 32	Week 32	Estimated mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 32
Body Weight at Week 32	Week 32	Estimated mean body weight after 32 Weeks of treatment
Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 10	Week 10	Proportion of subjects reaching HbA1c below 7.0% at Week 10
Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 21	Week 21	Proportion of subjects reaching HbA1c below 7.0% at Week 21
Fasting Plasma Glucose (FPG) at Week 10	Week 10	Mean FPG at Week 10
Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 10	Week 10	Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 10
Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 21	Week 21	Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 21
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21	Week 0, Week 21	Estimated mean change from baseline in HbA1c after 21 Weeks of treatment
Hypoglycaemic Episodes (Rate of All Treatment Emergent Hypoglycaemia Episodes)	Week 0 to Week 32	A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment.
Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 32	Week 32	Proportion of subjects reaching HbA1c below 7.0% at Week 32
Fasting Plasma Glucose (FPG) at Week 32	Week 32	Estimated Mean FPG at Week 32