Comparison of NN5401 Plus Insulin Aspart With Insulin Detemir Plus Insulin Aspart in Type 1 Diabetes

Phase 3

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 1

Interventions: Drug: insulin degludec/insulin aspart
Drug: insulin detemir
Drug: insulin aspart

Registration Number: NCT00978627

Lead Sponsor: Novo Nordisk A/S

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

The aim of this clinical trial is to compare NN5401 (insulin degludec/insulin aspart (IDegAsp)) with insulin detemir (IDet) plus insulin aspart in patients with type 1 diabetes (main period) followed by the extension period comparing the long-term safety of NN5401 plus insulin aspart with insulin detemir plus insulin aspart.

The main period is registered internally at Novo Nordisk as NN5401-3594 while the extension period is registered as NN5401-3645.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 548

Inclusion Criteria

FOR THE MAIN TRIAL, NN5401-3594:
Type 1 diabetes mellitus for at least 12 months
Ongoing daily treatment with insulin (in a basal bolus regimen, premix insulin regimen, self mix regimen) for at least 12 months
HbA1c 7.0-10.0% (both inclusive)
BMI (Body Mass Index) below or equal to 35.0 kg/m^2
FOR THE EXTENSION TRIAL, NN5401-3645:
The subject must have completed the six-month treatment period in trial NN5401-3594

Exclusion Criteria

FOR THE MAIN TRIAL, NN5401-3594:
Treatment with other insulin regimens than insulin in a basal bolus regimen/premix insulin regimen/self mix regimen 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 according to local requirements
Cancer and medical history of cancer
FOR THE EXTENSION TRIAL, NN5401-3645:
Anticipated significant lifestyle changes during the trial
Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IDegAsp OD	insulin degludec/insulin aspart	-
IDegAsp OD	insulin aspart	-
IDet	insulin detemir	-
IDet	insulin aspart	-

Primary Outcome Measures

Name	Time	Method
Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	Week 0, Week 26	Change from baseline in HbA1c after 26 weeks of treatment
Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	Week 0 to Week 53 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were 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 53 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs)	Week 0 to Week 53 + 7 days of follow up	Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: 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
Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	Week 0 to Week 26 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26	Week 26	Overall mean of 9-point SMPG at 26 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): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment	Week 0, Week 53	Change from baseline in HbA1c after 52 weeks of treatment
Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	Week 0 to Week 26 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.
Extension Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment	Week 0, Week 53	Change from baseline in FPG after 52 weeks of treatment.