Clinical Trials Register

Summary
EudraCT Number:	2016-000878-38
Sponsor's Protocol Code Number:	NN1218-4113
National Competent Authority:	Croatia - MIZ
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-11-06
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Croatia - MIZ

A.2

EudraCT number

2016-000878-38

A.3

Full title of the trial

Efficacy and Safety of Fast-acting Insulin Aspart Compared to NovoRapid® both in Combination with Insulin Degludec with or without Metformin in Adults with Type 2 Diabetes

Djelotvornost i sigurnost brzodjelujućeg aspart inzulina u usporedbi s lijekom NovoRapid®, oba u kombinaciji s degludek inzulinom s ili bez metformina u odraslih sa šećernom bolešću tipa 2

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Research study comparing a new medicine "fast-acting insulin aspart" to another already
available medicine NovoRapid® in people with type 2 diabetes

Ispitivanje koje uspoređuje novi lijek "brzodjelujući aspart inzulin" s drugim dostupnim lijekom NovoRapid® u pacijenata sa šećernom bolešću tipa 2

A.3.2

Name or abbreviated title of the trial where available

onset® 9

A.4.1

Sponsor's protocol code number

NN1218-4113

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1180-0636

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novo Nordisk A/S
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novo Nordisk A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novo Nordisk A/S
B.5.2	Functional name of contact point	Global Clinical Registry (GCR,1452)
B.5.3	Address:
B.5.3.1	Street Address	Novo Allé
B.5.3.2	Town/ city	Bagsværd
B.5.3.3	Post code	2880
B.5.3.4	Country	Denmark
B.5.6	E-mail	clinicaltrials@novonordisk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fiasp®
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Insulin Aspart
D.3.9.1	CAS number	116094-23-6
D.3.9.3	Other descriptive name	INSULIN ASPART
D.3.9.4	EV Substance Code	SUB08195MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NovoRapid
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Insulin Aspart
D.3.9.1	CAS number	116094-23-6
D.3.9.3	Other descriptive name	INSULIN ASPART
D.3.9.4	EV Substance Code	SUB08195MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tresiba®
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Insulin Degludec
D.3.9.1	CAS number	844439-96-9
D.3.9.3	Other descriptive name	INSULIN DEGLUDEC
D.3.9.4	EV Substance Code	SUB96394
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diabetes Mellitus, Type 2

Šećerna bolest tipa 2

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes

Šećerna bolest tipa 2

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II diabetes mellitus
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To confirm the effect in terms of glycaemic control of treatment with fast-acting insulin aspart compared to NovoRapid® both in combination with insulin degludec with or without metformin in adults with type 2 diabetes treated with a basal-bolus regimen, using a non-inferiority approach.

Potvrditi djelotvornost, u smislu glikemijske kontrole, liječenja brzodjelujućim aspart inzulinom u usporedbi s lijekom NovoRapid® , oba u kombinaciji s degludek inzulinom s ili bez metformina u odraslih sa šećernom bolešću tipa 2, koji se već liječe bazal-bolusom, koristeći pristup ne-inferiornosti.

E.2.2

Secondary objectives of the trial

1. To confirm superiority of fast-acting insulin aspart compared to NovoRapid® both in combination
with insulin degludec with or without metformin in adults with type 2 diabetes treated with a basal-bolus regimen in terms of:
- Postprandial glucose regulation
- Overall glycaemic control
- Postprandial glucose excursions

2. To compare the safety of fast-acting insulin aspart to NovoRapid® both in combination with insulin degludec with or without metformin in adults with type 2 diabetes treated with a basal-bolus regimen.

1. Potvrditi superiornost brzodjelujućeg aspart inzulina u odnosu na NovoRapid®, oba u kombinaciji s degludek inzulinom, s ili bez metformina u odraslih sa šećernom bolešću tipa 2, koji se već liječe bazal-bolusom u smislu:
-Regulacije postprandijalne glukoze
-Sveukupnu kontrolu glikemije
-Odstupanja postprandijalne glukoze

2. Usporediti sigurnost brzodjelujućeg aspart inzulina u usporedbi s lijekom NovoRapid® , oba u kombinaciji s degludek inzulinom s ili bez metformina u odraslih sa šećernom bolešću tipa 2, koji se već liječe bazal-bolusom

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female, age ≥ 18 years at the time of signing informed consent.
- Diagnosed with type 2 diabetes ≥ 10 years prior to screening (Visit 1).
- Treated with a basal-bolus insulin regimen ≥ 365 days prior to the day of screening (Visit 1). A basal-bolus insulin regimen is defined as basal insulin once or twice daily and bolus insulin analogue taken with meals at least 3 times daily. Treatment with premixed insulin or soluble insulin combination is not considered a basal-bolus regimen.
- Treated with or without oral antidiabetic drugs including extended release formulations. If treated with metformin, the total daily prescribed dose must have been stable for at least 90 days prior to screening (Visit 1).
- HbA1c 7.0-10.0% (both inclusive) as assessed by central laboratory at screening (Visit 1).

Randomisation criterion:
- HbA1c ≤ 9.0% measured by the central laboratory at Visit 13 (week -1).

-Muškarci i žene u dobi ≥ 18 godina u vrijeme potpisivanja Informiranog pristanka
-Dijagnoza šećerne bolesti tipa 2 ≥ 10 godina prije probira (posjet 1)
-Liječenje bazal-bolusom ≥ 365 dana prije probira. Bazal-bolus je definiran kao uzimanje balazlog inzulina jednom ili dvaput dnevno, a analog bolus inzulina se uzima uz obrog barem tri puta dnevno.
-Liječenje s ili bez oralnih antidijabetika uključujući i formulacije s produljenim oslobađanjem. Ukloliko liječenje uključuje metformin, propisana dnevna doza mora biti ustaljena barem 90 dana prije probira (posjet 1)
-HbA1c 7.0 – 10,0% (obje vrijednosti uključene)

Randomizacijski kriteriji:
-HbA1c ≤ 9.0% izmjereno od strane centralnog laboratorija na 13. posjetu (tjedan -1).

E.4

Principal exclusion criteria

- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening (Visit 1).
- Subjects presently classified as being in New York Heart Association (NYHA) Class IV.
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening (Visit 1).
- Treatment with injectable GLP-1 receptor agonists in a period of 90 days prior to screening (Visit 1).
- 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).

- Bilo što od sljedećeg: infarkt miokarda, moždani udar, hospitalizacija zbog nestabilne angine ili prolaznog ishemijskog napada u proteklih 180 dana prije dana probira (posjet 1)
- Pacijenti koji su klasificirani u New York Heart Association (NYHA) klasa IV
- Planirana revaskularizacija koronarnih, karotidnih ili perifernih arterija, poznata na dan probira (posjet 1)
- Liječenje injekcijskim GLP-1 agonistima u periodu od 90 dana prije probira (posjet 1)
- Predviđeno uvođenje ili promjena popratnih lijekova (više od 14 uzastopnih dana) koji poznato utječu na težinu ili metabolizam glukoze (npr. liječenje orlistatom, tiroidnim hormonima ili kortikosteroidima)

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in HbA1c

Promjena HbA1c od početnih vrijednosti do vrijednosti nakon zadanog vremena

E.5.1.1

Timepoint(s) of evaluation of this end point

16 weeks after randomisation

16 tjedana liječenja

E.5.2

Secondary end point(s)

1. Change from baseline in 1-hour postprandial glucose increment (meal test)
2. Change from baseline in 1,5-anhydroglucitol

1. Promjena jednosatnog prirasta postprandijalne glukoze (PPG) od početnih vrijednosti do vrijednosti nakon zadanog vremena
2. Promjena 1,5-anhidroglucitola od početnih vrijednosti do vrijednosti nakon zadanog vremena

E.5.2.1

Timepoint(s) of evaluation of this end point

1.-2. 16 weeks after randomisation

1.-2. 16 tjedana liječenja

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Treat-to-target

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Canada

European Union

Korea, Republic of

Russian Federation

Serbia

Ukraine

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

965

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

107

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

471

F.4.2.2

In the whole clinical trial

1262

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-08-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-01-29

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