Comparison of Two NN5401 Formulations Versus Biphasic Insulin Aspart 30, All in Combination With Metformin in Subjects With Type 2 Diabetes - Full Text View

Purpose

This trial is conducted in Europe. The aim of this trial is to compare two NN5401 (Soluble Insulin Analogue Combination [SIAC], insulin degludec/insulin aspart) formulations with each other and with biphasic insulin aspart 30, all in combination with metformin in insulin naive subjects with type 2 diabetes.

Condition	Intervention	Phase
Diabetes Diabetes Mellitus, Type 2	Drug: insulin degludec/insulin aspart Drug: biphasic insulin aspart Drug: metformin	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A 16 Week Randomised, Open Labelled, 3-armed, Parallel Group, Treat-to-target Trial Comparing Twice Daily (BID) Injections of SIAC 30 (B), SIAC 45 (B) and NovoMix®30, All in Combination With Metformin in Subjects With Type 2 Diabetes Failing on OAD Treatment

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Insulin Insulin human Insulin aspart Insulin degludec

U.S. FDA Resources

Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:

Change in Glycosylated Haemoglobin (HbA1c) [ Time Frame: Week 0, Week 16 ] [ Designated as safety issue: No ]
Change from baseline in HbA1c after 16 weeks of treatment

Secondary Outcome Measures:

Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Estimate of the overall 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, before bedtime, at 4 am and before breakfast.
Rate of Major and Minor Hypoglycaemic Episodes [ Time Frame: Week 0 to Week 16 + 5 days follow up ] [ Designated as safety issue: No ]
Observed 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.
Rate of Nocturnal Major and Minor Hypoglycaemic Episodes [ Time Frame: Week 0 to Week 16 + 5 days follow up ] [ Designated as safety issue: No ]
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 05:59 (included).
Rate of Treatment Emergent Adverse Events (AEs) [ Time Frame: Week 0 to Week 16 + 5 days follow up ] [ Designated as safety issue: No ]
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.
Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) [ Time Frame: Week -4, Week 16 ] [ Designated as safety issue: No ]
Laboratory values at screening (Week -4) and at Week 16
Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) [ Time Frame: Week -4, Week 16 ] [ Designated as safety issue: No ]
Laboratory values at screening (Week -4) and at Week 16
Laboratory Safety Parameters (Biochemistry): Serum Creatinine [ Time Frame: Week -4, Week 16 ] [ Designated as safety issue: No ]
Laboratory values at screening (Week -4) and at Week 16
Vital Signs: Diastolic Blood Pressure (BP) [ Time Frame: Week 0, Week 16 ] [ Designated as safety issue: No ]
Values at baseline (Week 0) and at Week 16
Vital Signs: Systolic Blood Pressure (BP) [ Time Frame: Week 0, Week 16 ] [ Designated as safety issue: No ]
Values at baseline (Week 0) and at Week 16
Vital Signs: Pulse [ Time Frame: Week 0, Week 16 ] [ Designated as safety issue: No ]
Values at baseline (Week 0) and at Week 16
Physical Examination [ Time Frame: Week -4, Week 8, Week 16 ] [ Designated as safety issue: No ]
Physical examination was performed at screening (week -4), 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.


Enrollment:	182
Study Start Date:	January 2008
Study Completion Date:	August 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: SIAC 30 (B)	Drug: insulin degludec/insulin aspart Formulation B: Treat-to-target dose titration scheme, injection s.c., twice daily Drug: metformin Tablets, 1500-2000 mg/daily
Experimental: SIAC 45 (B)	Drug: insulin degludec/insulin aspart Formulation B: Treat-to-target dose titration scheme, injection s.c., twice daily Drug: metformin Tablets, 1500-2000 mg/daily
Active Comparator: BIAsp 30	Drug: biphasic insulin aspart Treat-to-target dose titration scheme, injection s.c., twice daily Drug: metformin Tablets, 1500-2000 mg/daily

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 months at a stable maximally tolerated dose or at least half maximally 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) treatment within previous 3 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 (except for conditions associated with type 2 diabetes) that, in the opinion of the investigator, may confound the results of the trial or pose additional risk in administering trial product

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00613951

Locations


Finland

Lahti, Finland, 15110
France

Narbonne, France, 11108
Germany

Riesa, Germany, 01587
Poland

Warszawa, Poland, 02-507
Spain

Madrid, Spain, 28034

Sponsors and Collaborators

Novo Nordisk A/S

Investigators


Study Director:	Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Niskanen L, Leiter LA, Franek E, Weng J, Damci T, Muñoz-Torres M, Donnet JP, Endahl L, Skjøth TV, Vaag A. Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes: a randomised trial. Eur J Endocrinol. 2012 Aug;167(2):287-94. doi: 10.1530/EJE-12-0293. Epub 2012 Jun 1. Erratum in: Eur J Endocrinol. 2012 Sep;167(3):453.


Responsible Party:	Novo Nordisk A/S
ClinicalTrials.gov Identifier:	NCT00613951 History of Changes
Other Study ID Numbers:	NN5401-1792 2007-002462-35
Study First Received:	January 30, 2008
Results First Received:	October 16, 2015
Last Updated:	November 27, 2015
Health Authority:	Finland: Finnish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Spain: Spanish Agency of Medicines Germany: Federal Institute for Drugs and Medical Devices Poland: Ministry of Health

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Insulin, Globin Zinc Insulin degludec, insulin aspart drug combination Insulin aspart, insulin aspart protamine drug combination 30:70	Insulin Metformin Insulin Aspart Insulin, Long-Acting Biphasic Insulins Hypoglycemic Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016