Clinical Trials Register

Summary
EudraCT Number:	2015-001047-36
Sponsor's Protocol Code Number:	NN1218-4131
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-02-16
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-001047-36

A.3

Full title of the trial

Efficacy and Safety of Faster-acting Insulin Aspart compared to NovoRapid® both in combination with Insulin Degludec in Adults with Type 1 Diabetes

Efficacia e Sicurezza dell’Insulina Aspart ad azione ultra-rapida in confronto con NovoRapid® entrambi in combinazione con Insulina Degludec in Adulti con Diabete Mellito tipo 1

A.3.1

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

Efficacy and Safety of Faster-acting Insulin Aspart compared to NovoRapid® both in combination with Insulin Degludec in Adults with Type 1 Diabetes

Efficacia e Sicurezza dell’Insulina Aspart ad azione ultra-rapida in confronto con NovoRapid® entrambi in combinazione con Insulina Degludec in Adulti con Diabete Mellito tipo 1

A.3.2

Name or abbreviated title of the trial where available

onset®8

A.4.1

Sponsor's protocol code number

NN1218-4131

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1167-9495

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. S.P.A.
B.1.3.4	Country	Italy
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 Allè,
B.5.3.2	Town/ city	Bagsværd
B.5.3.3	Post code	2880
B.5.3.4	Country	Denmark
B.5.4	Telephone number	N/A
B.5.5	Fax number	N/A
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	No
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.3.1	Product name	Faster aspart 3ml PDS290
D.3.2	Product code	null
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULINA ASPART
D.3.9.1	CAS number	116094-23-6
D.3.9.2	Current sponsor code	NN1218
D.3.9.3	Other descriptive name	INSULINA 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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 - FLEXPEN 100 U/ML SOLUZIONE INIETTABILE 5 CARTUCCE IN PENNE PRERIEMPITE 3 ML USO SOTTOCUTANEO
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	Italy
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.3.1	Product name	Novorapid
D.3.2	Product code	null
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULINA ASPART
D.3.9.1	CAS number	116094-23-6
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	INSULINA 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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 - 100 U/ML-SOLUZIONE INIETTABILE-USO SOTTOCUTANEO-PENNA PRE-RIEMPITA (VETRO)(FLEXTOUCH)- 3 ML - 5 PENNE PRERIEMPITE
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	Italy
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.3.1	Product name	Tresiba
D.3.2	Product code	null
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULINA DEGLUDEC
D.3.9.1	CAS number	844439-96-9
D.3.9.2	Current sponsor code	NN1250
D.3.9.3	Other descriptive name	INSULINA 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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 1

Diabete mellito tipo 1

E.1.1.1

Medical condition in easily understood language

Type 1 diabetes

Diabete tipo 1

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045228
E.1.2	Term	Type I 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 efficacy in terms of glycaemic control of treatment with mealtime faster-acting insulin aspart in combination with insulin degludec in adults with Type 1 Diabetes Mellitus.

Confermare l’efficacia nel controllo glicemico di insulina aspart ad azione ultra-rapida
somministrata al pasto in combinazione con insulina degludec negli adulti con diabete mellito
di tipo 1.

E.2.2

Secondary objectives of the trial

To confirm efficacy in terms of glycaemic control of treatment with postmeal faster-acting insulin aspart in combination with insulin degludec in adults with Type 1 Diabetes Mellitus.

To confirm superiority of mealtime faster-acting insulin aspart compared to mealtime NovoRapid® both in combination with insulin degludec in adults with Type 1 Diabetes Mellitus in terms of:
- Postprandial glucose regulation (meal test)
- Postprandial glucose excursions (1,5-anhydroglucitol)
- Overall glycaemic control (HbA1c)

To compare other efficacy and safety endpoints across mealtime faster-acting insulin aspart, postmeal faster-acting insulin aspart and mealtime NovoRapid®, all in combination with insulin degludec in adults with Type 1 Diabetes Mellitus.

Confermare l’efficacia nel controllo glicemico di insulina aspart ad azione ultra-rapida
somministrata dopo il pasto in combinazione con insulina degludec negli adulti con diabete
mellito di tipo 1.
 Confermare la superiorità di insulina aspart ad azione ultra-rapida somministrata al pasto
rispetto a NovoRapid®, entrambi in combinazione con insulina degludec negli adulti con
diabete mellito di tipo 1 in termini di:
- regolazione della glicemia postprandiale [Postprandial Glucose, PPG] (Meal test)
- Variazioni glicemiche postprandiali (1,5-anidroglucitolo)
- Controllo della glicemia (HbA1c)
 Confrontare altri endpoint di efficacia e sicurezza di insulina aspart ad azione ultra-rapida
somministrata al pasto, somministrata dopo il pasto e NovoRapid® somministrata al
pasto, tutti in combinazione con insulina degludec negli adulti con diabete mellito di tipo 1.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, age ≥ 18 years (for Japan and Taiwan: age ≥20 years) at the time of signing informed consent
2. Type 1 Diabetes Mellitus (based on clinical judgement and/or supported by laboratory analysis as per local guidelines) ≥12 months prior to screening
3. Currently treated with a basal-bolus insulin regimen for at least 12 months prior to screening (Visit 1)
4. Currently treated with a basal insulin analogue for at least 4 months prior to screening (Visit 1)
5. HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory
6. Body Mass Index ≤ 35.0 kg/m^2

1.Uomini o donne con età ≥ 18 anni al momento della firma del consenso informato.
2. Diagnosi di diabete mellito di tipo 1 (basata sul giudizio clinico e/o supportata da analisi di
laboratorio in accordo alle linee guida vigenti) ≥ 12 mesi prima dello screening.
3. Trattamento basal-bolus in corso da almeno 12 mesi prima dello screening.
4. Trattamento con analogo basale dell’insulina in corso da almeno 4 mesi prima dello
screening.
5. Valori di HbA1c 7,0-9,5% (estremi compresi) analizzati dal Laboratorio centrale alla visita 1
di screening.
6. Indice di massa corporea ≤ 35,0 kg/m2.

E.4

Principal exclusion criteria

1. Within the past 180 days any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischemic attack
2. Subjects presently classified as being in New York Heart Association (NYHA) Class IV Currently planned coronary, carotid or peripheral artery revascularisation
3. Diabetic ketoacidosis requiring hospitalisation within the last 180 days prior to screening (Visit 1)
4. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of three months before screening (Visit 1)

1.Qualsiasi dei seguenti eventi verificatisi entro gli ultimi 180 giorni: infarto del miocardio,
ictus o ricovero in ospedale per angina instabile e/o attacco ischemico transitorio (TIA).
2.Insufficienza cardiaca, New York Heart Association (NYHA) di classe IV.
3.Chetoacidosi diabetica che ha richiesto il ricovero in ospedale entro gli ultimi 180 giorni
dallo screening (Visita 1)
4.Trattamento con qualsiasi farmaco indicato per il diabete o l’obesità, diverso da quelli
stabiliti nei criteri di inclusione, nei tre mesi precedenti lo screening (Visita 1)

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in HbA1c

Variazione del valore iniziale dell’HbA1c dopo 26 settimane di trattamento.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 26 weeks of treatment

Dopo 26 settimane di trattamento.

E.5.2

Secondary end point(s)

Change from baseline in 1-hour post prandial glucose increment (meal test)

Change from baseline in 1,5-anhydroglucitol

Variazione rispetto al valore iniziale dell’incremento della glicemia postprandiale a 1 ora (meal test).

Variazione rispetto al valore iniziale della glicemia plasmatica a digiuno

E.5.2.1

Timepoint(s) of evaluation of this end point

After 26 weeks of treatment

dopo 26 settimane di trattamento.

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

Due bracci in doppio cieco, un braccio in aperto, treat to target

Two arms double-blinded, one arm open, 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

Information not present in EudraCT

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

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

Number of subjects for this age range:

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

900

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

300

F.4.2.2

In the whole clinical trial

999

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
Please refer to protocol section 5.4

Si prega di consultare la sezione 5.4 del Protocollo.

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

2015-11-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-10

P. End of Trial
P.	End of Trial Status	Completed

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Orphan Designation Number:
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