A trial comparing effect and safety of insulin degludec/insulin aspart vs. insulin glargine plus insulin aspart in subjects with type 2 diabetes treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2015-004768-12-CZ
• Date of registration: 25/05/2016
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A trial comparing effect and safety of insulin degludec/insulin aspart vs. insulin glargine plus insulin aspart in subjects with type 2 diabetes treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification
• Scientific title: A 38 week trial comparing effect and safety of insulin degludec/insulin aspart vs. insulin glargine plus insulin aspart in subjects with type 2 diabetes treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification
• Date of first enrolment: 10/08/2016
• Target sample size: 528
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004768-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Treat-to-target design; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Czech Republic, India, Russian Federation, Serbia, Turkey, United States

Contacts

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

Key inclusion & exclusion criteria

Inclusion criteria:
1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
2. Male or female, age = 18 years at the time of signing informed consent. Algeria: Male or female, age = 19 years at the time of signing informed consent
3. Diagnosed with type 2 diabetes mellitus
4. Treated with any basal insulin = 90 days prior to the day of screening
5. Subject not on any OAD(s) prior to trial participation OR subjects on stable daily dose(s) of OAD(s) for at least 90 days prior to screening visit (V1). The OAD(s) include any of the following anti-diabetic drug(s)/regimen:
a. Biguanides (metformin = 1500 mg or maximum tolerated dose documented in the subject medical record)
b. Other OADs (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record):
i. Insulin secretagogues (SU and glinides)
ii. Di-peptidyl-peptidase IV (DPP-4) inhibitors
iii. a-glucosidase inhibitors
iv. Sodium/glucose co-transporter 2 (SGLT-2) inhibitors
v. Oral combination products (of the allowed individual OADs above)
6. HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) by central laboratory analysis
7. Body mass index (BMI) = 45.0 kg/m^2

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 396
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132

Exclusion criteria:
1. Participation in any clinical trial of an approved or non-approved investigational medicinal product within four weeks prior to the day of screening (V1)
2. Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject’s safety or compliance with the protocol
3. Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g. diabetes ketoacidosis) = 90 days prior to the day of the screening and between screening and randomisation
4. Any of the following: myocardial infarction , stroke or hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and between screening and randomisation
5. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of < 60 ml/min/1.73 m^2 as defined by KDIGO 2012 classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening
6. Impaired liver function, defined as alanine aminotransferase (ALT) = 2.5 times upper normal limit (UNL) at screening.
7. Subjects presently classified as being in New York Heart Association (NYHA) Class IV
8. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
9. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening.
10. Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2
MedDRA version: 19.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Ryzodeg® 100 units/mL solution for injection in pre-filled pen
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INSULIN ASPART
CAS Number: 116094-23-6
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: INSULIN DEGLUDEC
CAS Number: 844439-96-9
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Lantus® SoloStar® 100 units/ml solution for injection in pre-filled pen
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INSULIN GLARGINE
CAS Number: 160337-95-1
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: NovoRapid® FlexPen® 100 units/ml solution for injection in pre-filled pen
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INSULIN ASPART
CAS Number: 116094-23-6
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): Change in glycosylated haemoglobin (HbA1c) (%)

Main Objective: To confirm the effect of insulin degludec/insulin aspart once daily versus insulin glargine once daily in combination with insulin aspart once daily in controlling glycaemia after 26 weeks in subjects with type 2 diabetes mellitus treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification

Secondary Objective: 1. To compare other effect parameters and safety of insulin degludec/insulin aspart once daily versus insulin glargine once daily in combination with insulin aspart once daily after 26 weeks in subjects with type 2 diabetes mellitus treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification.
2. To compare the effect and safety of insulin degludec/insulin aspart once daily or twice daily versus insulin glargine once daily in combination with insulin aspart (1-3 times daily) after 38 weeks in subjects with type 2 diabetes mellitus treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification.

Timepoint(s) of evaluation of this end point: From baseline after 26 weeks

Secondary Outcome(s)

Secondary end point(s): 1. Responder (Yes/No) for HbA1c < 7%
2. Change from baseline in HbA1c (%)
3. Responder (Yes/No) for HbA1c < 7%
4. Number of treatment-emergent severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes
5. Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes
6. Incidence of treatment-emergent adverse events (TEAEs)

Timepoint(s) of evaluation of this end point: 1. After 26 weeks
2. After 38 weeks
3. After 38 weeks
4. During 26 weeks
5. During 38 weeks
6. During 38 weeks

Secondary ID(s)

NN5401-4266

Source(s) of Monetary Support

Novo Nordisk A/S