Comparison of Two NN5401 Formulations Versus Insulin Glargine, All in Combination With Metformin in Subjects With Type 2 Diabetes

Phase 2

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 2

Interventions: Drug: insulin degludec/insulin aspart
Drug: insulin glargine
Drug: metformin

Registration Number: NCT00614055

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Europe. The aim of this trial is to compare two NN5401 (SIAC, insulin degludec/insulin aspart) formulations with each other and with insulin glargine, all in combination with metformin in insulin naive subjects with type 2 diabetes.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 178

Inclusion Criteria

Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
Insulin naïve type 2 diabetes subjects (as diagnosed clinically) for at least 3 months (no previous insulin treatment or previous short term insulin treatment maximum 14 days within the last 3 months)
Treatment with one or two oral anti-diabetic drugs (OADs): metformin, sulfonylurea, other insulin secretagogue (e.g. repaglinide, nateglinide), alpha-glucosidase inhibitors for at least 2 month at a stable maximum tolerated dose or at least half maximum allowed dose according to locally approved summary of product characteristics (SPC)
HbA1c, 7.0 - 11.0 % (both inclusive)
Body Mass Index (BMI), 25.0 - 37.0 kg/m^2 (both inclusive)

Exclusion Criteria

Metformin contraindication according to local practice
Thiazolidinedione (TZD) treatments within the previous three months prior to Visit 1
Any systemic treatment with products, which in the investigator's opinion could interfere with glucose or lipid metabolism (e.g. systemic corticosteroids) within 3 months prior to randomisation
Subject has a clinically significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary, or haematological system that, in the opinion of the investigator, may confound the results of the trial or pose additional risk in administering trial product

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SIAC 30 (B)	insulin degludec/insulin aspart	-
SIAC 45 (B)	insulin degludec/insulin aspart	-
Insulin glargine	metformin	-
Insulin glargine	insulin glargine	-
SIAC 30 (B)	metformin	-
SIAC 45 (B)	metformin	-

Primary Outcome Measures

Name	Time	Method
Change in Glycosylated Haemoglobin (HbA1c)	Week 0, Week 16	Change from baseline in HbA1c after 16 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Rate of Treatment Emergent Adverse Events (AEs)	Week 0 to Week 16 + 5 days 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.
Change in Fasting Plasma Glucose (FPG)	Week 0, Week 16	Change from baseline in FPG after 16 weeks of treatment
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)	Week 16	Mean of SMPG after 16 weeks of treatment. Plasma glucose measured: before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, bedtime, at 4 am and before breakfast.
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes	Week 0 to Week 16 + 5 days follow up	Rate of nocturnal Major and Minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Episodes were defined as nocturnal if the time of onset was between 23:00 (included) and 06:00 (excluded).
Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT)	Week -4, Week 16	Values at screening (Week -4) and at Week 16
Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT)	Week -4, Week 16	Values at screening (Week -4) and at Week 16
Laboratory Safety Parameters (Biochemistry): Serum Creatinine	Week -4, Week 16	Values at screening (Week -4) and at Week 16
Vital Signs: Diastolic Blood Pressure (BP)	Week 0, Week 16	Values at baseline (Week 0) and at Week 16
Vital Signs: Systolic Blood Pressure (BP)	Week 0, Week 16	Values at baseline (Week 0) and at Week 16
Vital Signs: Pulse	Week 0, Week 16	Values at baseline (Week 0) and at Week 16
Physical Examination	Week 0, Week 8, Week 16	Physical examination is performed at baseline (Week 0) and after 8 and 16 weeks of treatment. If any new findings or deterioration in previous findings were observed during the trial, these were recorded as AEs and are therefore not presented separately as no analysis was performed.
Rate of Major and Minor Hypoglycaemic Episodes	Week 0 to Week 16 + 5 days follow up	Rate of Major and Minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L.