Clinical Trials Register

Summary
EudraCT Number:	2021-001167-24
Sponsor's Protocol Code Number:	TRS-2019-00002051
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-08-17
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2021-001167-24

A.3

Full title of the trial

Intraclass safety and efficacy comparison among SGLT-2 inhibitors in elderly patients with type 2 diabetes. A pragmatic, phase IV, multicenter, open-label, randomised controlled trial.

Confronto intraclasse di sicurezza ed efficacia tra inibitori di SGLT-2 in pazienti anziani affetti da diabete tipo 2. Trial randomizzato pragmatico di fase IV, multicentrico, in aperto.

A.3.1

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

Comparison among SGLT-2 inhibitors in elderly patients with type 2 diabetes.

Confronto tra farmaci inibitori di SGLT-2 in pazienti anziani affetti da diabete tipo 2.

A.3.2

Name or abbreviated title of the trial where available

GOLDEN-AGE

A.4.1

Sponsor's protocol code number

TRS-2019-00002051

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	SID - Società Italiana di Diabetologia e Malattie del Metabolismo
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	AIFA - Italian Medicines Agency
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	SID
B.5.2	Functional name of contact point	Segreteria
B.5.3	Address:
B.5.3.1	Street Address	Via Pisa, 21
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00162
B.5.3.4	Country	Italy
B.5.6	E-mail	a.russo@siditalia.it

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.2.5	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	Dapagliflozin
D.3.2	Product code	[Dapagliflozin]
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	DAPAGLIFLOZIN
D.3.9.2	Current sponsor code	Dapagliflozin
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.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.2.5	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	Canagliflozin
D.3.2	Product code	[Canagliflozin]
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	CANAGLIFLOZIN
D.3.9.2	Current sponsor code	Canagliflozin
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	100 to 300
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: 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.2.5	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	Empagliflozin
D.3.2	Product code	[Empagliflozin]
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	Emagliflozin
D.3.9.2	Current sponsor code	Emagliflozin
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	10 to 25
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

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

diabetes

Diabete

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	10045252
E.1.2	Term	Type II diabetes mellitus without mention of complication
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

The primary objective is to compare the proportion of patients treated with each SGLT2i drug, who achieve the individualized HbA1c target without level-3 hypoglycaemia at the end of the study at 24 months0

L'obiettivo principale è confrontare la percentuale di pazienti trattati con ciascun farmaco SGLT2i, che raggiungono l'obiettivo di HbA1c individualizzato senza ipoglicemia di livello 3 alla fine dello studio a 24 mesi.

E.2.2

Secondary objectives of the trial

The primary secondary objective will be to compare the proportion of patients treated with each SGLT2i drug, who achieve the individualized HbA1c target without level-2 hypoglycemia at any time during the observation.
Other secondary objectives include the intra-class comparison of several study endpoints: Change in HbA1c level, in body weight, in systolic blood pressure, in e-GFR, in urinary albumin excretion rate in concomitant medications and their daily dosages, in treatment satisfaction quantified as Diabetes Treatment Satisfaction Questionnaire (DTSQ), Plasma/serum biomarkers of bone metabolism and cardiac function (in a subset of patients), including BNP, beta-crosslaps, acid phosphatase, alkaline phosphatase, serum calcium, serum phosphorus, osteocalcin.

L'obiettivo primario secondario sarà confrontare la proporzione di pazienti trattati con ciascun farmaco SGLT2i, che raggiungono il target di HbA1c individualizzato senza ipoglicemia di livello 2 in qualsiasi momento durante l'osservazione.
Altri obiettivi secondari includono il confronto intra-classe di diversi endpoint dello studio: variazione del livello di HbA1c, del peso corporeo, della pressione sanguigna sistolica, dell'e-GFR, del tasso di escrezione urinaria di albumina nei farmaci concomitanti e dei loro dosaggi giornalieri, nella soddisfazione del trattamento quantificata come Diabetes Treatment Satisfaction Questionnaire (DTSQ), biomarcatori plasmatici / sierici del metabolismo osseo e della funzione cardiaca (in un sottogruppo di pazienti), inclusi BNP, beta-crosslaps, fosfatasi acida, fosfatasi alcalina, calcio sierico, fosforo sierico, osteocalcina.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Type 2 diabetes
- Age =70 years
- Men or women
- Established cardiovascular disease (symptomatic or asymptomatic) or eGFR <90 ml / min / 1.73 m2 but above the threshold for starting therapy with all SGLTe inhibitors
- HbA1c higher than the individualized target value
- Clinical indication when starting a therapy with SGLT2i
- Ability to give written informed consent.

- Diabete tipo 2
- Età =70 anni
- Uomini o donne
- Malattia cardiovascolare accertata (sintomatica o asintomatica) o eGFR <90 ml/min/1.73 m2 ma sopra la soglia per l’avvio della terapia con tutti gli inibitori di SGLTe
- HbA1c superiore rispetto al valore target individualizzato
- Indicazione clinica all’avvio di una terapia con SGLT2i
- Capacità di prestare consenso informato scritto.

E.4

Principal exclusion criteria

- Age> 90 years
- Estimated life expectancy <1 year
- Very high risk of urinary infections (more than 2 episodes in the last 6 months)
- Recent unintentional weight loss (> 5% in <6 months)
- Participation in another interventional drug trial
- Inability to give written informed consent
- Intolerance to lactose and any other contraindication to the study drugs

- Età >90 anni
- Aspettativa di vita stimata <1 anno
- Rischio molto alto di infezioni urinarie (più di 2 episodi negli ultimi 6 mesi)
- Recente calo ponderale non intenzionale (>5% in <6 mesi)
- Partecipazione in un altro trial interventistico con farmaco
- Incapacità di prestare consenso informato scritto
- Intolleranza al lattosio e qualsiasi altra controindicazione ai farmaci in studio

E.5 End points

E.5.1

Primary end point(s)

Glucose control without level-3 hypoglycemia

Controllo del glucosio senza ipoglicemia di livello 3

E.5.1.1

Timepoint(s) of evaluation of this end point

At any time during observation

Ad ogni momento durante l'osservazione

E.5.2

Secondary end point(s)

Glucose control without level-2 hypoglycemia; Change in HbA1c glycemic and extraglycemic endpoints; Change in HbA1c; Change in body weight; Change in systolic blood pressure; Change in eGFR; Change in the use of concomitant medications; Change in the dosage of concomitant medications; Change in treatment satisfaction; Safety:
- Hospitalization for any cause,
- Hospitalization for heart failure,
- Hospitalization for cardiovascular causes,
- All-cause death
- Cardiovascular death
- Severe hypoglycemia
- Genitourinary tract infections
- Dehydration / hypovolemia events
- Bone fractures;
- Leg/foot amputations
- Diabetic ketoacidosis

Controllo del glucosio senza ipoglicemia di livello 2; Modifica degli endpoint glicemici ed extraglicemici di HbA1c; Modifica nei valori di HbA1c; Modifica nel peso corporeo; Modifica nella pressione sistolica; MOdifica del eGFR; Modifica nell'uso dei farmaci concomitanti; Modifica nelle dosi dei farmaci concomitanti; Modifica nella soddisfazione del trattamento; Sicurezza:
- Ricovero per qualsiasi causa,
- Ricovero per insufficienza cardiaca,
- Ricovero per cause cardiovascolari,
- Morte per tutte le cause
- Morte cardiovascolare
- Grave ipoglicemia
- Infezioni del tratto genito-urinario
- Eventi di disidratazione / ipovolemia
- Fratture ossee;
- Amputazioni di gambe / piedi
- Chetoacidosi diabetica

E.5.2.1

Timepoint(s) of evaluation of this end point

At any time during observation; Mean least square difference at 24 months; Mean least square difference at 24 months; Mean least square difference at 24 months; Mean least square difference at 24 months; Mean least square difference at the end of observation; At 24 months; Mean least square difference at 24 months; Mean least square difference at 24 months; At 24 months

Ad ogni momento durante l'osservazione; Differenza quadratica minima media a 24 mesi; Differenza quadratica minima media a 24 mesi; Differenza quadratica minima media a 24 mesi; Differenza quadratica minima media a 24 mesi; Differenza quadratica minima media a 24 mesi; A 24 mesi; Differenza quadratica minima media a 24 mesi; Differenza quadratica minima media a 24 mesi; A 24 mesi

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

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

Comparison

Confronto

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

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

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

For each given patient the study will end after completion of the maximum 36 month follow-up period, or at study closure. The trial will end when the last patient has completed the minimum 12 month follow-up. Last visit of the last patient will identify conclusion of trial procedures. No trial extension is planned, but may be added in due course, if deemed appropriate, subject to protocol amendment.

Per ogni dato paziente lo studio terminerà dopo il completamento del periodo massimo di 36 mesi di follow-up, o alla chiusura dello studio. Lo studio terminerà quando l'ultimo paziente avrà completato il follow-up minimo di 12 mesi. L'ultima visita dell'ultimo paziente identificherà la conclusione delle procedure di prova. Non è prevista alcuna estensione dello studio, ma può essere aggiunta a tempo debito, se ritenuto opportuno, previa modifica del protocollo.

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:

1167

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

1167

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1167

F.4.2.2

In the whole clinical trial

1167

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)

Patients with a clinical indication for the addition of an SGLT2 inhibitor will be randomized to receive canagliflozin, dapagliflozin or empagliflozin alone or in combination. The dosage will be chosen by the treating physician and individualized according to clinical indication.

Pazienti con un'indicazione clinica all'aggiunta di un inibitore SGLT2 saranno randomizzati a ricevere canagliflozin, dapagliflozin o empagliflozin da soli o in associazione. Il dosaggio sarà scelto dal medico curante ed individualizzato secondo indicazione clinica.

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

2021-08-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-04

P. End of Trial
P.	End of Trial Status	Trial now transitioned

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials