Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
1,167
Countries
1
Sites
32
Type 2 diabetes mellitus
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
Key facts
- Sponsor
- Center For Outcomes Research And Clinical Epidemiology S.r.l.
- Participant type
- Patients
- Age range
- 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Trial duration
- 16 Feb 2022 → 2 Oct 2025
- Decision date (initial)
- 2024-11-13
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- SID Società Italiana Diabetologia
External identifiers
- EU CT number
- 2024-518915-20-00
- EudraCT number
- 2021-001167-24
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
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
Secondary objectives 1
- 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.
Conditions and MedDRA coding
Type 2 diabetes mellitus
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10045252 | Type II diabetes mellitus without mention of complication | 10027433 |
| 20.0 | SOC | 10014698 | Endocrine disorders | 5 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | randomization Participants will be randomly assigned (1:1:1) to either canagliflozin, dapagliflozin, or empagliflozin (alone or in combination with metformin, as deemed clinically appropriate). Computer generated randomization lists will be used. Permuted blocks randomization will be done centrally via an interactive web system and will be stratified by site.
|
Randomised Controlled | None | 1: Canagliflozin If the patient is already on metformin, the fixed combination Canagliflozin / Metformin can be used. 2: Dapagliflozin If the patient is already on metformin, the fixed combination dapagliflozin / metformin can be used. 3: Empagliflozin If the patient is already on metformin, the fixed combination empagliflozin / metformin can be used. |
|
| 2 | Follow up Patients will continue on the investigational product or stop it at discretion of the treating diabetologist. Patients will be followed up according to routine care at each participating Center. The duration of SGLT- 2i prescription within the National Health System at the time the protocol was approved for funding and at the time of first application for ethical approval, was 6 months. Thus, it is expected that patients will be seen at routine control visits every 6 months to refill prescriptions with “piano terapeutico”.
|
Randomised Controlled | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- 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.
Exclusion criteria 7
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Glucose control without level-3 hypoglycemia
Secondary endpoints 10
- 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
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 16
Vokanamet 50 mg/850 mg film-coated tablets
PRD1575802 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD16 — -
- Marketing authorisation
- EU/1/14/918/003
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Synjardy 12.5 mg/850 mg film-coated tablets
PRD3223872 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD20 — -
- Marketing authorisation
- EU/1/15/1003/027
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Vokanamet 50 mg/1,000 mg film-coated tablets
PRD1575799 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD16 — -
- Marketing authorisation
- EU/1/14/918/004
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Synjardy 5 mg/850 mg film-coated tablets
PRD3459097 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD20 — -
- Marketing authorisation
- EU/1/15/1003/037
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Xigduo 5 mg/1,000 mg film-coated tablets
PRD1181102 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD15 — -
- Marketing authorisation
- EU/1/13/900/007
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Synjardy 12.5 mg/1,000 mg film-coated tablets
PRD3227984 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD20 — -
- Marketing authorisation
- EU/1/15/1003/034
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Invokana 300 mg film-coated tablets
PRD3349143 · Product
- Active substance
- Canagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 600 mg milligram(s)
- Max total dose
- 600 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BK02 — -
- Marketing authorisation
- EU/1/13/884/008
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Vokanamet 150 mg/1,000 mg film-coated tablets
PRD1575801 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD16 — -
- Marketing authorisation
- EU/1/14/918/010
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Invokana 100 mg film-coated tablets
PRD3349139 · Product
- Active substance
- Canagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BK02 — -
- Marketing authorisation
- EU/1/13/884/002
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Xigduo 5 mg/850 mg film-coated tablets
PRD1181117 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD15 — -
- Marketing authorisation
- EU/1/13/900/001
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Jardiance 10 mg film-coated tablets
PRD1594848 · Product
- Active substance
- Empagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BK03 — -
- Marketing authorisation
- EU/1/14/930/010
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Vokanamet 150 mg/850 mg film-coated tablets
PRD1575800 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD16 — -
- Marketing authorisation
- EU/1/14/918/007
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Synjardy 5 mg/1,000 mg film-coated tablets
PRD3459049 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BD20 — -
- Marketing authorisation
- EU/1/15/1003/038
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Jardiance 25 mg film-coated tablets
PRD1594891 · Product
- Active substance
- Empagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BK03 — -
- Marketing authorisation
- EU/1/14/930/001
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Forxiga 10 mg film-coated tablets
PRD2427550 · Product
- Active substance
- Dapagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BK01 — -
- Marketing authorisation
- EU/1/12/795/009
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Forxiga 5 mg film-coated tablets
PRD2466459 · Product
- Active substance
- Dapagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BK01 — -
- Marketing authorisation
- EU/1/12/795/001
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Center For Outcomes Research And Clinical Epidemiology S.r.l.
- Sponsor organisation
- Center For Outcomes Research And Clinical Epidemiology S.r.l.
- Address
- Corso Umberto Primo 103
- City
- Pescara
- Postcode
- 65122
- Country
- Italy
Scientific contact point
- Organisation
- Center For Outcomes Research And Clinical Epidemiology S.r.l.
- Contact name
- Antonio Nicolucci
Public contact point
- Organisation
- Center For Outcomes Research And Clinical Epidemiology S.r.l.
- Contact name
- Antonio Nicolucci
Locations
1 EU/EEA country · 32 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ended | 1,167 | 32 |
| Rest of world | — | 0 | — |
Investigational sites
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
SSD Malattie del metabolismo e diabetologia, Regione Gonzole 10, 10043, Orbassano
Azienda Ospedaliero Universitaria Ospedali Riuniti
Dipartiento medicina specialistica malattie endocrine, Viale Luigi Pinto 1, 71122, Foggia
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
centro malattie endocrine e metaboliche, Largo Francesco Vito 1, 00168, Rome
Ospedale Santa Maria Goretti Latina
UOC diabetologia universitaria, Viale Michelangelo Buonarroti, 04100, Latina
ARNAS Garibaldi Di Catania
UO endocrinologia, Piazza Santa Maria Di Gesu, 95123, Catania
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Centro aterosclerosi, Viale Oxford 81, 00133, Rome
ARNAS Garibaldi Di Catania
UOC medicina interna, Piazza Santa Maria Di Gesu, 95123, Catania
Azienda Ospedaliera Universitaria Integrata Verona
Endocrinologia diabetologia malattie del metabolismo, Piazzale Aristide Stefani 1, 37126, Verona
Azienda Ospedaliero Universitaria Parma
UOC endocrinologia e malattie del metabolismo, Viale Antonio Gramsci 14, 43126, Parma
Ospedale San Raffaele S.r.l.
Cardio-metabolismo e trials clinici, Via Olgettina 60, 20132, Milan
Azienda Unita' Locale Socio Sanitaria N. 2 Marca Trevigiana
UOC Malattie endocrine metaboliche e della nutrizione, Piazzale Ospedale 1, 31100, Treviso
Azienda Unita' Locale Socio Sanitaria N. 2 Marca Trevigiana
UOC Malattie endocrine metaboliche e della nutrizione, Via Brigata Bisagno 4, 31015, Conegliano
Azienda Ospedaliera Universitaria Senese
UOC Diabetologia, Viale Mario Bracci 2, 53100, Siena
IRCCS Ospedale Policlinico San Martino
Endocrinologia, Largo Rosanna Benzi 10, 16132, Genoa
ASST Fatebenefratelli Sacco
UOSD malattie endocrine e diabetologia, Piazzale Principessa Clotilde 3, 20121, Milan
Azienda Ospedaliera di Padova
Dipartimento di Medicina, Via Nicolo' Giustiniani 2, 35128, Padova
Azienda Ospedaliero Universitaria Pisana
Medicina 1, Via Roma 67, 56126, Pisa
Azienda Sanitaria Locale Di Pescara
Dipartimento endocrinologia e malattie metaboliche, Via Renato Paolini 47, 65124, Pescara
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
UOC malattie endocrine 1-diabetologia, Piazza Oms 1, 24127, Bergamo
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
UO endocrinologia, Via Francesco Sforza 35, 20122, Milan
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G Salesi
SOD clinica di endocrinologia e malattie del metabolismo, Via Filippo Corridoni 11, 60123, Ancona
Azienda Ospedaliera Universitaria Federico II Di Napoli
reparto di diabetologia, Via Sergio Pansini 5, 80131, Naples
Policlinico Di Monza S.p.A.
Medicina metabolica, Via Carlo Amati 111, 20900, Monza
Fondazione IRCCS Policlinico San Matteo
Endocrinologia e diabetologia, Viale Camillo Golgi 19, 27100, Pavia
ASST Grande Ospedale Metropolitano Niguarda
SSD Diabetologia, Piazza Dell'ospedale Maggiore 3, 20162, Milan
University Of Bari Aldo Moro
UOC di endocrinologia, Piazzale Giulio Cesare 11, 70124, Bari
Azienda Ospedaliero Universitaria Pisana
UO Malattie metaboliche e diabetologia, Via Roma 67, 56126, Pisa
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
UOC Malattie endocrine del ricambio e della nutrizione, Via Del Vespro 129, 90127, Palermo
Azienda Ospedaliera Policlinico Universitario Tor Vergata
UOC endocrinologia e diabetologia, Viale Oxford 81, 00133, Rome
Azienda Ospedaliera Universitaria Federico II Di Napoli
Medicina interna e diabetologia, Via Sergio Pansini 5, 80131, Naples
Azienda Ospedaliero-Universitaria Maggiore Della Carita
SCDU Endocrinologia, Corso Giuseppe Mazzini 18, 28100, Novara
Azienda Ospedaliero-Universitaria Policlinico Umberto I
UOD Diabetologia, Viale Del Policlinico 155, 00161, Rome
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2022-02-16 | 2025-10-02 | 2022-02-16 | 2025-08-06 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-518915-20-00 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Forxiga | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Invokana | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Jardiance | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Synjardy | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Vokanamet | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Xigduo | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2024-518915-20-00 | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-15 | Italy | Acceptable 2024-11-05
|
2024-11-13 |
| 2 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-11-20 | Italy | Acceptable | 2025-02-28 |
| 3 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-06-16 | Italy | Acceptable | 2025-08-06 |
| 4 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-08-28 | Italy | Acceptable | 2025-09-30 |