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

• ClinicalTrials.gov Identifier: NCT00613951
• Recruitment Status: Completed
• First Posted: February 13, 2008
• Results First Posted: December 1, 2015
• Last Update Posted: March 20, 2017
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: insulin degludec/insulin aspart; Drug: biphasic insulin aspart; Drug: metformin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: January 2008
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: August 2008

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Change in Glycosylated Haemoglobin (HbA1c) [ Time Frame: Week 0, Week 16 ]
   Change from baseline in HbA1c after 16 weeks of treatment

Secondary Outcome Measures :

1. Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) [ Time Frame: Week 16 ]
   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.
2. Rate of Major and Minor Hypoglycaemic Episodes [ Time Frame: Week 0 to Week 16 + 5 days follow up ]
   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.
3. Rate of Nocturnal Major and Minor Hypoglycaemic Episodes [ Time Frame: 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 05:59 (included).
4. Rate of Treatment Emergent Adverse Events (AEs) [ Time Frame: 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.
5. Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) [ Time Frame: Week -4, Week 16 ]
   Laboratory values at screening (Week -4) and at Week 16
6. Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) [ Time Frame: Week -4, Week 16 ]
   Laboratory values at screening (Week -4) and at Week 16
7. Laboratory Safety Parameters (Biochemistry): Serum Creatinine [ Time Frame: Week -4, Week 16 ]
   Laboratory values at screening (Week -4) and at Week 16
8. Vital Signs: Diastolic Blood Pressure (BP) [ Time Frame: Week 0, Week 16 ]
   Values at baseline (Week 0) and at Week 16
9. Vital Signs: Systolic Blood Pressure (BP) [ Time Frame: Week 0, Week 16 ]
   Values at baseline (Week 0) and at Week 16
10. Vital Signs: Pulse [ Time Frame: Week 0, Week 16 ]
    Values at baseline (Week 0) and at Week 16
11. Physical Examination [ Time Frame: Week -4, Week 8, Week 16 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Finland

Novo Nordisk Investigational Site

Helsinki, Finland, 00260

Novo Nordisk Investigational Site

Kuopio, Finland, 70210

Novo Nordisk Investigational Site

Lahti, Finland, 15110

Novo Nordisk Investigational Site

Pori, Finland, FI-28100

France

Novo Nordisk Investigational Site

Bar-Le-Duc, France, 55000

Novo Nordisk Investigational Site

GRENOBLE cedex, France, 38043

Novo Nordisk Investigational Site

Hayange, France, 57700

Novo Nordisk Investigational Site

LA ROCHELLE cedex, France, 17019

Novo Nordisk Investigational Site

Nanterre, France, 92014

Novo Nordisk Investigational Site

NEVERS cedex, France, 58033

Novo Nordisk Investigational Site

Pointe à Pitre, France, 97159

Germany

Novo Nordisk Investigational Site

Berlin, Germany, 12163

Novo Nordisk Investigational Site

Pirna, Germany, 01796

Novo Nordisk Investigational Site

Riesa, Germany, 01587

Novo Nordisk Investigational Site

Saarbrücken, Germany, 66121

Novo Nordisk Investigational Site

St. Ingbert, Germany, 66386

Novo Nordisk Investigational Site

Völklingen, Germany, 66333

Novo Nordisk Investigational Site

Wangen, Germany, 88239

Poland

Novo Nordisk Investigational Site

Bydgoszcz, Poland, 85-822

Novo Nordisk Investigational Site

Gniewkowo, Poland, 88-140

Novo Nordisk Investigational Site

Nysa, Poland, 48-300

Novo Nordisk Investigational Site

Plock, Poland, 09-400

Novo Nordisk Investigational Site

Szczecin, Poland, 70-483

Novo Nordisk Investigational Site

Tychy, Poland, 43-100

Novo Nordisk Investigational Site

Warszawa, Poland, 02-507

Novo Nordisk Investigational Site

Wroclaw, Poland, 50-127

Spain

Novo Nordisk Investigational Site

Almería, Spain, 04001

Novo Nordisk Investigational Site

Barcelona, Spain, 08035

Novo Nordisk Investigational Site

Granada, Spain, 18012

Novo Nordisk Investigational Site

Madrid, Spain, 28034

Novo Nordisk Investigational Site

San Juan, Spain, 03550

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 

Publications of Results:

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.

Ma Z, Parkner T, Christiansen JS, Laursen T. IDegAsp: a novel soluble insulin analogs combination. Expert Opin Biol Ther. 2012 Nov;12(11):1533-40. doi: 10.1517/14712598.2012.722203. Epub 2012 Sep 4. Review.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00613951 History of Changes
• Other Study ID Numbers: NN5401-1792; 2007-002462-35 ( EudraCT Number )
• First Posted: February 13, 2008
• Results First Posted: December 1, 2015
• Last Update Posted: March 20, 2017
• Last Verified: February 2017

Additional relevant MeSH terms:

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