Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes

Phase 3

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 2

Interventions: Drug: insulin glargine
Drug: insulin degludec
Drug: insulin aspart

Registration Number: NCT00972283

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Africa, Asia, Europe, and the United States of America (USA).

The aim of this clinical trial is to compare NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar) plus insulin aspart (IAsp) with/without metformin and with/without pioglitazone in subjects with type 2 diabetes (main period) followed by investigating the long-term safety in terms of comparing NN1250 with insulin glargine plus insulin aspart with or without metformin and with or without pioglitazone in subjects with type 2 diabetes.

All oral anti-diabetic drug (OAD) treatment will be discontinued, if applicable, when trial participant enters the trial (NN1250-3582) with the exception of metformin and pioglitazone.

Subjects who consent to participate in the extension trial (NN1250-3667) will continue to receive the treatment to which they were randomly allocated in the 52 week trial NN1250-3582.

The main period is registered internally at Novo Nordisk as NN1250-3582 while the extension period is registered as NN1250-3667.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1006

Inclusion Criteria

For MAIN period (NN1250-3582):
Type 2 diabetes mellitus for at least 6 months
Ongoing daily treatment with insulin (premix, self-mix, basal only, basal bolus) for at least 3 months with/without oral anti-diabetics drug (OAD) prior to trial start
HbA1c 7.0-10.0 % (both inclusive)
Body Mass Index (BMI) below or equal to 40.0 kg/m^2
For EXTENSION period (NN1250-3667):
Completion of the 52 week treatment period in NN1250-3582

Exclusion Criteria

For MAIN period (NN1250-3582):
Treatment with other insulin regimens than premix, self-mix, basal only, basal bolus within 3 months
Cardiovascular disease within the last 6 months
Uncontrolled treated/untreated severe hypertension
Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures
Cancer and medical history of cancer

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IGlar OD	insulin aspart	-
IGlar OD	insulin glargine	-
IDeg OD	insulin degludec	-
IDeg OD	insulin aspart	-

Primary Outcome Measures

Name	Time	Method
Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment	Week 0, Week 52	Change from baseline in HbA1c after 52 weeks of treatment
Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	Week 0 to Week 78 + 7 days follow up	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	Week 0 to Week 78 + 7 days follow up	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.
Rate of Treatment Emergent Adverse Events (AEs)	Week 0 to Week 78 + 7 days follow up	Corresponds to rate of AEs per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious adverse event (SAE): AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.

Secondary Outcome Measures

Name	Time	Method
Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 78 Weeks of Treatment	Week 0, Week 78	Change from baseline in HbA1c after 78 weeks of treatment
Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	Week 0 to Week 52 + 7 days follow up	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.
Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52	Week 52	Mean of 9-point SMPG at 52 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.
Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 78	Week 78	Mean of the SMPG at 78 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am, before breakfast.
Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	Week 0 to Week 52 + 7 days follow up	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.