Clinical trial NCT01513590: A Trial Comparing Efficacy and Safety of Insulin Degludec/Insulin Aspart and BIAsp 30 in Insulin naïve Subjects With Type 2 Diabetes
Official title: A 26-week, Randomised, Open-label, Multinational, Treat-to-target Trial Comparing Efficacy and Safety of Insulin Degludec/Insulin Aspart (IDegAsp) Twice Daily (BID) and BIAsp 30 BID Both With Metformin in Insulin naïve Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Monotherapy or Metformin in Combination With One Additional Oral Antidiabetic Drug (OAD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2012-01-20
Enrollment: 394
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Africa, Asia and Europe. The aim of the trial is to compare the efficacy and safety of insulin degludec/insulin aspart and BIAsp 30 (biphasic insulin aspart 30) in insulin naïve subjects with type 2 diabetes.


Eligibility 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)
* Type 2 diabetes mellitus (diagnosed clinically) for at least 24 weeks prior to screening
* Current treatment: metformin monotherapy or metformin in any combination with one of the following oral anti-diabetic drugs (OADs): insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV (DPP-IV) inhibitor, alpha-glucosidase inhibitors for at least 12 weeks prior to randomisation (Visit 2) with the minimum doses stated: - Metformin: alone or in combination (including fixed combination) 1500 mg daily, or maximum tolerated dose (at least 1000 mg daily), - Insulin secretagogue (sulphonylurea or glinide): minimum half of the daily maximum dose according to local labelling, - DPP-IV inhibitor: minimum 100 mg daily or according to local labelling, - Alpha-glucosidase-inhibitors: minimum half of the daily maximum dose or maximum tolerated dose
* Insulin naïve subject; allowed is: Previous short term insulin treatment up to 14 days
* Insulin naïve subject; allowed is: Treatment during hospitalization or during gestational diabetes is allowed for periods longer than 14 days)
* HbA1c (glycosylated haemoglobin) between 7.0-10.0 % (both inclusive) by central laboratory analysis
* Body mass index (BMI) below or equal to 40.0 kg/m\^2

Exclusion Criteria:

* Treatment with thiazolidinediones (TZDs) or glucagon like peptide 1 (GLP-1) receptor agonists within 12 weeks prior to visit 1 (screening)
* Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers and MAO inhibitors
* Anticipated significant lifestyle changes during the trial according to the discretion of the trial physician, e.g. shift work (including permanent night/evening shift workers), as well as highly variable eating habits
* Cardiovascular disease, within the last 24 weeks prior to trial start, defined as: stroke; decompensated heart failure NYHA (New York Heart Association) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty
* Any clinically significant disease or disorder, except for conditions associated with type 2 diabetes, which in the trial physician's opinion could interfere with the results of the trial
* Previous participation in this trial. Participation is defined as randomised. Re-screening of screening failures is allowed only once within the limits of the recruitment period
* Known or suspected hypersensitivity to trial products or related products

Primary outcomes:
measure: Change From Baseline in HbA1c (Glycosylated Haemoglobin)
timeFrame: Week 0, week 26
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 26
measure: Number of Treatment Emergent Nocturnal (00:01-05:59 am) Severe or Minor Hypoglycaemic Episodes
timeFrame: Onset on or after the first day of exposure to investigational product and no later than 7 days after last exposure to investigational product
measure: Number of Severe and Minor Treatment Emergent Hypoglycaemic Episodes
timeFrame: Onset on or after the first day of exposure to investigational product and no later than 7 days after last exposure to investigational product
measure: Change From Baseline in Body Weight
timeFrame: Week 0, week 26
measure: Responder for HbA1c (Below 7.0%) Without Severe and Minor Treatment Emergent Hypoglycaemic Episodes During the Last 12 Weeks of Treatment Including Only Subjects Exposed for at Least 12 Weeks
timeFrame: Week 26
measure: Number of Treatment Emergent AEs (Adverse Events)
timeFrame: Onset on or after the first day of exposure to investigational product and no later than 7 days after exposure to investigational product
Other outcomes:
Locations:
city: Algiers
country: Algeria
facility: Novo Nordisk Investigational Site
city: Oran
country: Algeria
facility: Novo Nordisk Investigational Site
city: Setif
country: Algeria
facility: Novo Nordisk Investigational Site
city: Haskovo
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Lukovit
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Plovdiv
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Ruse
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Karlovac
country: Croatia
facility: Novo Nordisk Investigational Site
city: Osijek
country: Croatia
facility: Novo Nordisk Investigational Site
city: Rijeka
country: Croatia
facility: Novo Nordisk Investigational Site
city: Zadar
country: Croatia
facility: Novo Nordisk Investigational Site
city: Zagreb
country: Croatia
facility: Novo Nordisk Investigational Site
city: Brno
country: Czechia
facility: Novo Nordisk Investigational Site
city: Hradec Kralove
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 10
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha
country: Czechia
facility: Novo Nordisk Investigational Site
city: Bochum
country: Germany
facility: Novo Nordisk Investigational Site
city: Hohenmölsen
country: Germany
facility: Novo Nordisk Investigational Site
city: Rehlingen-Siersburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Saint Ingbert-Oberwürzbach
country: Germany
facility: Novo Nordisk Investigational Site
city: Völklingen
country: Germany
facility: Novo Nordisk Investigational Site
city: Wangen
country: Germany
facility: Novo Nordisk Investigational Site
city: Bialystok
country: Poland
facility: Novo Nordisk Investigational Site
city: Lublin
country: Poland
facility: Novo Nordisk Investigational Site
city: Lublin
country: Poland
facility: Novo Nordisk Investigational Site
city: Mazowieckie
country: Poland
facility: Novo Nordisk Investigational Site
city: Warszawa
country: Poland
facility: Novo Nordisk Investigational Site
city: Oradea
country: Romania
facility: Novo Nordisk Investigational Site
state: Bihor
city: Bucharest
country: Romania
facility: Novo Nordisk Investigational Site
city: Buzau
country: Romania
facility: Novo Nordisk Investigational Site
city: Galati
country: Romania
facility: Novo Nordisk Investigational Site
city: Sibiu
country: Romania
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Kosice
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Antalya
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Kocaeli
country: Turkey
facility: Novo Nordisk Investigational Site
city: Dnipro
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Kyiv
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Lviv
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Poltava
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Poltava
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Vinnytsia
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Zhytomyr
country: Ukraine
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Franek E, Haluzik M, Canecki Varzic S, Sargin M, Macura S, Zacho J, Christiansen JS. Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naive adults with Type 2 diabetes. Diabet Med. 2016 Apr;33(4):497-505. doi: 10.1111/dme.12982. Epub 2015 Nov 17.
citation: Christiansen JS, Niskanen L, Rasmussen S, Johansen T, Fulcher G. Lower rates of hypoglycemia during maintenance treatment with insulin degludec/insulin aspart versus biphasic insulin aspart 30: a combined analysis of two Phase 3a studies in type 2 diabetes. J Diabetes. 2016 Sep;8(5):720-8. doi: 10.1111/1753-0407.12355. Epub 2016 Mar 6.
citation: Haluzik M, Fulcher G, Pieber TR, Bardtrum L, Tutkunkardas D, Rodbard HW. The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase III studies in patients with type 2 diabetes. Diabetes Obes Metab. 2018 Jul;20(7):1585-1592. doi: 10.1111/dom.13261. Epub 2018 Mar 25.
citation: Yang W, Akhtar S, Franek E, Haluzik M, Hirose T, Kalyanam B, Kar S, Wu T, Gogas Yavuz D, Unnikrishnan AG. Postprandial Glucose Excursions in Asian Versus Non-Asian Patients with Type 2 Diabetes: A Post Hoc Analysis of Baseline Data from Phase 3 Randomised Controlled Trials of IDegAsp. Diabetes Ther. 2022 Feb;13(2):311-323. doi: 10.1007/s13300-021-01196-7. Epub 2022 Jan 19.