Clinical Trials Register

Summary
EudraCT Number:	2014-005639-15
Sponsor's Protocol Code Number:	NN9068-4228
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:	2021-02-17
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

2014-005639-15

A.3

Full title of the trial

A 104 week clinical trial comparing long term glycaemic control of insulin degludec/liraglutide (IDegLira) versus insulin glargine therapy in subjects with type 2 diabetes mellitus

Studio clinico di 104 settimane per confrontare il controllo glicemico a lungo termine della terapia con insulina degludec/liraglutide (IDegLira) rispetto alla terapia con insulina glargine in soggetti con diabete mellito di tipo 2

A.3.1

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

A clinical trial comparing long term glycaemic control of insulin degludec/liraglutide (IDegLira) versus insulin glargine therapy in subjects with type 2 diabetes mellitus

Studio clinico per confrontare il controllo glicemico a lungo termine della terapia con insulina degludec/liraglutide (IDegLira) rispetto alla terapia con insulina glargine in soggetti con diabete mellito di tipo 2

A.3.2

Name or abbreviated title of the trial where available

DUAL ™ VIII - Durability

DUAL TM VIII - Studio di lunga durata

A.4.1

Sponsor's protocol code number

NN9068-4228

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1165-3914

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	Bagsvaerd
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	Yes
D.2.1.1.1	Trade name	Xultophy
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	INSULINA DEGLUDEC
D.3.9.1	CAS number	844439-96-9
D.3.9.2	Current sponsor code	NN1250
D.3.9.4	EV Substance Code	SUB96394
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LIRAGLUTIDE
D.3.9.1	CAS number	204656-20-2
D.3.9.2	Current sponsor code	NN2211
D.3.9.4	EV Substance Code	SUB25238
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
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	Lantus
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-aventis
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	INSULINA GLARGINE
D.3.9.1	CAS number	160337-95-1
D.3.9.4	EV Substance Code	SUB08196MIG
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 2

Diabete mellito di tipo 2

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes

Diabete di tipo 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	21.1
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 compare long-term glycaemic control of insulin degludec/liraglutide (IDegLira) versus insulin glargine (IGlar) in insulin naïve subjects with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OAD[s]).

L' obiettivo primario dello studio è confrontare il controllo glicemico a lungo termine di IDegLira con IGlar in soggetti insulino-naïve con T2DM non adeguatamente controllati con OAD.

E.2.2

Secondary objectives of the trial

To compare long-term efficacy and safety of IDegLira versus IGlar in insulin naïve subjects with T2DM inadequately controlled with OAD(s).

L' obiettivo secondario dello studio è confrontare l' efficacia e la sicurezza a lungo termine di IDegLira in soggetti insulino-naïve con T2DM non adeguatamente controllati con OAD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female, age > or =18 years at the time of signing informed consent
- Subjects diagnosed with type 2 diabetes mellitus
- HbA1c 7.0-11.0% (both inclusive) (53–97 mmol/mol) by central laboratory analysis
- Body mass index > o = 20 kg/m^2
- Insulin naïve subjects; however short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
- Stable daily dose(s) including any of the following antidiabetic drug(s)/regimens within 90 days prior to the day of screening:
o Biguanides (metformin > o = 1500 mg or maximum tolerated dose documented in the subject medical record)
o Other OAD(s) allowed: sulphonylurea, glinides, pioglitazone, and DPP4-inhibitors ( > o = half of the maximum approved dose according to local label or maximum tolerated dose as documented in subjects medical record)

- Sesso maschile o femminile, > o = 18 anni di età al momento della firma del consenso informato
- Soggetti a cui è stato diagnosticato (clinicamente) diabete mellito di tipo 2 prima del giorno dello screening
- HbA1c 7,0-11,0% (estremi compresi) analizzato presso il laboratorio centrale
- Indice di massa corporea (Body Mass Index, BMI)
- Soggetti insulino-naïve; tuttavia è consentito il trattamento a breve termine con insulina per un periodo massimo di 14 giorni prima del giorno dello screening, così come il trattamento precedente con insulina per diabete gestazionale
- Dose/i stabile/i quotidiana/e di qualsiasi farmaco/regime antidiabetico tra i seguenti, nei 90 giorni precedenti al giorno dello screening:
o Biguanidi (metformina > o = 1.500 mg o dose massima tollerata documentata nella cartella clinica del soggetto)
o Altri OAD consentiti: sulfonilurea, glinidi, pioglitazone e inibitori DPP4 ( > o = metà della dose massima approvata secondo l’etichetta locale o dose massima tollerata come documentato dalla cartella medica del soggetto)

E.4

Principal exclusion criteria

- Screening calcitonin > or = 50 ng/L
- Renal impairment estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73 m2 as per CKD-EPI value to be defined as listed in the classification CKD-EPI using IDMS for serum creatinine measurement on the day of screening
- Impaired liver function, defined as ALAT or ASAT > or = 2.5 times upper limit of normal
- Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma
- History of pancreatitis (acute or chronic)
- 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
- Anticipated initiation or change in concomitant medications for more than 14 consecutive days or on a frequent basis known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids)

- Valore della calcitonina allo screening > o = 50 ng/l
- Velocità di filtrazione glomerulare stimata per insufficienza renale (Glomerular Filtration Rate, eGFR) < 60 ml/min/1,73 m2 come per il valore di collaborazione epidemiologica per insufficienza renale cronica (Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI) da definire in base all’elenco della classificazione CKD-EPI mediante spettrometria di massa con diluizione isotopica (Isotope Dilution-Mass Spectrometry, IDMS) per la misurazione della creatinina sierica il giorno dello screening
- Funzione epatica ridotta, definita come alanina aminotransferasi (ALAT) o aspartato aminotransferasi (ASAT) > o = 2,5 volte il limite superiore di normalità
- Anamnesi familiare o personale di neoplasia endocrina multipla di tipo 2 o carcinoma midollare della tiroide
- Anamnesi di pancreatite (acuta o cronica).
- Trattamento con qualsiasi farmaco indicato per il diabete o l’obesità, diverso da quelli stabiliti nei criteri di inclusione, in un periodo di 90 giorni precedenti lo screening
- Inizio anticipato o variazione, per oltre 14 giorni consecutivi o su base frequente, nell’assunzione di farmaci concomitanti dei quali è nota l’influenza sul peso o sul metabolismo glicemico (ad es. orlistat, ormoni tiroidei, corticosteroidi)

E.5 End points

E.5.1

Primary end point(s)

Time from randomisation to inadequate glycaemic control and need for treatment intensification, defined as a glycosylated haemoglobin (HbA1c) of > or = 7.0% at 2 consecutive visits from week 26, including week.
26 if HbA1c was > or = 7% at week 12

Tempo dalla randomizzazione al controllo glicemico inadeguato e necessità di intensificazione del trattamento, definito come emoglobina glicosilata (HbA1c) > o = 7,0% a 2 visite consecutive dalla settimana 26 (compresa la settimana 26 se HbA1c fosse > o = 7% alla settimana 12).

E.5.1.1

Timepoint(s) of evaluation of this end point

Will be assessed up to 104 weeks.

L’endpoint primario verrà valutato in un periodo di 104 settimane.

E.5.2

Secondary end point(s)

Key supportive secondary efficacy endpoints:
1. Time from randomisation to an HbA1c > 6.5% at 2 consecutive visits
2. Change from baseline in:
o HbA1c
o body weight
o Fasting plasma glucose (FPG)
o 9-point Self-measured plasma glucose (SMPG) profile (individual
points in the profile)
3. Insulin dose
4. Responder (yes/no):
o HbA1c < 7.0%
o HbA1c < or = 6.5%

Key supportive secondary safety endpoints
5. Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes

L' endpoint secondario di efficacia è definito come:
1. il tempo trascorso dalla randomizzazione ad un valore di HbA1c > 6,5% a 2 visite consecutive
2. Variazione rispetto al basale di:
- HbA1c
- peso corporeo
- Glicemia a digiuno (Fasting Plasma Glucose, FPG)*
- Profilo glicemico a 9 punti misurato autonomamente (Self-Measured Plasma Glucose, SMPG)
3. Dose di insulina
4. Pazienti responsivi (Si/No):
- HbA1c < 7.0%
- HbA1c < o = 6.5%

L'endpoint secondario di sicurezza è deifinito come:
5. Numero di episodi ipoglicemici sintomatici gravi o confermati dal valore di glicemia nel sangue

E.5.2.1

Timepoint(s) of evaluation of this end point

1. From week 26
2. After 26 weeks of treatment
3. After 26 weeks of treatment
4. After 26 and 104 weeks of treatment
5. During 26 and 104 weeks of treatment

1. Dalla settimana 26
2. Dopo la settimana 26 di trattamento
3. Dopo la settimana 26 di trattamento
4. Dopo la settimana 26 e 104 di trattamento
5. Durante la settimana 26 e 104 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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

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

Argentina

Brazil

India

Israel

Mexico

Russian Federation

South Africa

Turkey

Norway

European Union

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:

900

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

300

F.4.2.2

In the whole clinical trial

1000

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

Nessuno

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

2015-12-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-09

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

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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