Clinical Trials Register

Summary
EudraCT Number:	2017-004663-12
Sponsor's Protocol Code Number:	PAOFIN2017
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-24
Trial 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

2017-004663-12

A.3

Full title of the trial

Geriatric outcomes among older Type 2 diabetic patients treated with DPP4 inhibitors or glinides: focus on cognitive functioning (GOOD-WP3)

Outcomes geriatrici in pazienti anziani affetti da diabete di tipo 2 trattati con gli inibitori DPP4 o le glinidi: focus sulla funzione cognitiva

A.3.1

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

Geriatric outcomes among older Type 2 diabetic patients treated with DPP4 inhibitors or glinides: focus on cognitive functioning (GOOD-WP3)

Outcomes geriatrici in pazienti anziani affetti da diabete di tipo 2 trattati con gli inibitori DPP4 o le glinidi: focus sulla funzione cognitiva

A.3.2

Name or abbreviated title of the trial where available

GOOD-WP3

A.4.1

Sponsor's protocol code number

PAOFIN2017

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	A.O.U. Università degli Studi della Campania "Luigi Vanvitelli"
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Ministero della Salute - Bando ricerca finalizzata - Italia
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Azienda Ospedaliera Universitaria "Luigi Vanvitelli"
B.5.2	Functional name of contact point	U.O.C. Geriatria e Medicina Interna
B.5.3	Address:
B.5.3.1	Street Address	piazza miraglia,2
B.5.3.2	Town/ city	Napoli
B.5.3.3	Post code	80138
B.5.3.4	Country	Italy
B.5.4	Telephone number	0815665138
B.5.5	Fax number	0815665303
B.5.6	E-mail	giuseppe.paolisso@unicampania.it

D. IMP Identification
D.IMP: 1
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	NOVONORM - 0.5 MG COMPRESSE-30 COMRESSE IN BLISTER
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	Novonorm
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	00248000
D.3.9.1	CAS number	135062-02-1
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Repaglinide
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	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	TRAJENTA - 5 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (ALU/ALU) 28 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BOEHRINGER INGELHEIM INTERNATIONAL GMBH
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	Trajenta
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	00323700
D.3.9.1	CAS number	668270-12-0
D.3.9.2	Current sponsor code	LN1
D.3.9.3	Other descriptive name	LINAGLIPTIN
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

type 2 diabetes mellitus

Diabete mellito di tipo 2

E.1.1.1

Medical condition in easily understood language

type 2 diabetes mellitus

Diabete mellito 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	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

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 assess the effects of linagliptin 5 mg once daily vs. repaglinide 0.5 mg thrice daily on cognitive and physical decline in older T2DM) subjects using a metformin therapy

Valutare gli effetti del linagliptin 5 mg una volta al giorno rispetto a repaglinide 0,5 mg tre volte al giorno sulla funzione cognitiva nei soggetti anziani con diabete di tipo 2 in terapia con metformina

E.2.2

Secondary objectives of the trial

To evaluate the impact of DPP$ or glinides on physical and cognitive decline

Valutare l'impatto delle DPP4 o glinidi sul declino fisico e cognitivo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

diagnosis of type 2 diabetes prior to informed consent; male and female patients who are pre-treated with an unchanged dose of metformin almost 4 weeks prior to randomization visit. Dose for metformin is defined as the maximum tolerated dose; age = 70 years; HbA1c =7.5%; risk of sarcopenia: low handgrip (men = 30.0 kg, women = 20.0 kg) or slow habitual walking speed (< 1m/s);

Diagnosi di diabete mellito di tipo 2; pazienti maschi e femmine pre-trattati con una dose invariata di metformina almeno 4 settimane prima della visita di randomizzazione. La dose di metformina è definita come dose massima tollerata; età = 70 anni; HbA1c = 7,5%; rischio di sarcopenia: basso handgrip (uomini = 30,0 kg, donne = 20,0 kg) o abituale lentezza nella velocità della camminata (<1m / s);

E.4

Principal exclusion criteria

diagnosis of type 1 diabetes mellitus; impaired kidney function (eGFR<30 ml/min per 1.73 m2); active malignancy within 24 months prior to screening; heart failure NYHA III-IV; use of GLP-1 agonists or DPP-IV therapy in the last 3 months.
history of pancreatitis; hepatic disease (liver function tests more than 3 times the upper limit of normal); chronic Obstructive Pulmonary Disease (COPD); uncontrolled hypertension (BP > 160/100 mm of Hg); known hypersensitivity to linagliptin and/or repaglinide or inactive ingredients; life expectancy less than 6 months; diagnosis of dementia; complete dependency in Basic Activities of Daily Living (BADL); participation in any other clinical trial; patients unwilling to provide consent and those who cannot be followed-up or unable to co-operate with the study procedures; treatment with anti-obesity drugs, systemic corticosteroids or nonsteroidal anti-inflammatory drugs, any other anti-diabetic medication including insulin therapy (except metformin).

Diagnosi di diabete mellito di tipo 1; funzione renale compromessa (eGFR < 30 ml/min per 1,73 m2); tumore maligno attivo nei 24 mesi precedenti lo screening; insufficienza cardiaca NYHA III-IV; uso di agonisti GLP-1 o terapia DPP-IV negli ultimi 3 mesi; pregressa pancreatite; patologie epatiche (i test di funzionalità epatica superano per più di 3 volte il limite superiore di normalità); bronco pneumopatia cronico ostruttiva (BPCO); ipertensione non controllata (BP> 160/100 mm di Hg); ipersensibilità nota a linagliptin e/o repaglinide o ingredienti inattivi; aspettativa di vita inferiore a 6 mesi; diagnosi di demenza; dipendenza completa nelle attività di base della vita quotidiana (BADL); partecipazione ad altri studi clinici pazienti non disposti a fornire il consenso e coloro che non possono effettuare il follow-up, oppure incapaci di eseguire le procedure previste dallo studio; trattamento con farmaci contro l'obesità, corticosteroidi sistemici o farmaci antinfiammatori non steroidei, qualsiasi altro medicinale anti-diabetico, inclusa la terapia insulinica (eccetto metformina).

E.5 End points

E.5.1

Primary end point(s)

Change from baseline after 24 weeks of treatment of incidence of major comorbidities, physical performance (SPPB), cognitive impairment (MMSE), risk of depression (GDS) before and after linagliptin use as compared to repaglinide.

Variazione rispetto al basale dopo 24 settimane di trattamento dell'incidenza delle principali comorbilità, prestazioni fisiche (SPPB), deterioramento cognitivo (MMSE), rischio di depressione (GDS) prima e dopo l'uso di linagliptin rispetto alla repaglinide.

E.5.1.1

Timepoint(s) of evaluation of this end point

Change from baseline after 24 weeks of treatment

Cambiamento rispetto al basale dopo 24 settimane di trattamento

E.5.2

Secondary end point(s)

Change from baseline after 24 weeks of treatment of:
• fasting plasma glucose (FPG)
• glycosylated hemoglobin (HbA1C)
• markers of inflammation and oxidative stress (TNF-a, IL1ß; IL6, IL18, nitrotyrosine)
• biological and molecular markers linked to diabetes (plasma and exosomal inflamma-miRs (Front Genet. 2013; 4: 121) such as Mir-21, Mir-126, Mir-146, Mir-181, AGE (advanced glycation endproducts), RAGE (receptor for advanced glycation endproducts)
• lean muscle mass (DEXA);
• incidence of major comorbidities;
• physical performance (SPPB);
• cognitive impairment (MMSE);
• risk of depression (GDS);
• malnutrition/undernutrition (MNA);
• health-related quality of life (EQ-5D);
• use of healthcare resources.

Cambiamenti rispetto ai valori rilevati al baseline dopo 24 settimane di trattamento di:
• glucosio plasmatico a digiuno (FPG)
• emoglobina glicosilata (HbA1C)
• marcatori di infiammazione e stress ossidativo (TNF-a, IL1ß; IL6, IL18, nitrotyrosine)
• marcatori biologici e molecolari legati al diabete (miRs infiammatori plasmatici ed esosomiali (Front Genet 2013, 4: 121) quali Mir-21, Mir-126, Mir-146, Mir-181, AGE (advanced glycation endproducts) RAGE (recettore per advanced glycation endproducts)
• massa muscolare magra (DEXA);
• l'incidenza delle principali comorbidità;
• performance fisica (SPPB);
• performance cognitiva (MMSE);
• rischio di depressione (GDS);
• malnutrizione/sottonutrizione (MNA);
• qualità della vita relativa allo stato di salute (EQ-5D);
• utilizzo di risorse sanitarie.

E.5.2.1

Timepoint(s) of evaluation of this end point

change from baseline after 24 weeks of treatment

Cambiamento rispetto al basale dopo 24 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

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

double dummy

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

146

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

F.3.3.1

Women of childbearing potential not using contraception

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

146

F.4.2

For a multinational trial

F.4.2.1

In the EEA

146

F.4.2.2

In the whole clinical trial

146

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)

At the end of the study the patiennts will continue to be followed at the research center clinic and treated according to the guidelines for the management of the elderly diabetic patient

Al termine dello studio i pazienti continueranno ad essere seguiti presso l'ambulatorio del centro di ricerca e trattati secondo le linee guida per la gestione del paziente anziano diabetico

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

2019-05-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-13

P. End of Trial
P.	End of Trial Status	Ongoing

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