Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruitment pending
Participants planned
135
Countries
1
Sites
3
Actinic keratoses
To determine the efficacy and safety of topical metformin as an adjuvant to daylight photodynamic therapy (dPDT) with methyl aminolevulinate (MAL) in the treatment of actinic keratoses and the cancerisation field.
Key facts
- Sponsor
- Fundacion Instituto De Investigacion Sanitaria Aragon
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Decision date (initial)
- 2025-01-30
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2025-520798-38-00
- EudraCT number
- 2021-004044-21
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To determine the efficacy and safety of topical metformin as an adjuvant to daylight photodynamic therapy (dPDT) with methyl aminolevulinate (MAL) in the treatment of actinic keratoses and the cancerisation field.
Secondary objectives 8
- To compare the efficacy of topical metformin adjuvant dPDT with MAL versus dPDT with MAL as monotherapy in actinic keratoses.
- To determine the most effective topical metformin concentration for adjuvant treatment of dPDT with MAL in actinic keratoses and the cancerisation field
- To compare the number of new actinic keratoses occurring in the cancerisation field treated with topical metformin combined with dPDT with MAL versus dPDT alone with MAL.
- To compare the adverse effects of adjuvant metformin of dPDT with MAL versus dPDT with MAL as monotherapy.
- To compare the change in actinic keratoses related quality of life induced by the combination of metformin with dPDT with MAL versus dPDT with MAL in monotherapy. This change will be determined by a questionnaire to be completed by subjects participating in the study.
- To compare the histological changes produced by the combination of topical metformin with dPDT with MAL versus dPDT alone with MAL.
- To assess the expression of resistance biomarkers in those actinic keratoses unresponsive to topical metformin combination therapy with dPDT versus those resistant to dPDT with MAL monotherapy.
- To determine patient satisfaction with topical metformin treatment in adjuvant dPDT with MAL versus only dPDT with MAL.
Conditions and MedDRA coding
Actinic keratoses
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Males or females over 18 years of age.
- Subjects with at least 5 actinic keratoses on face and/or scalp Olsen grade I and/or II (Olsen, 1991).
- If women of childbearing capacity participate, they must use an effective method of contraception throughout the study.
Exclusion criteria 11
- Patients with predominantly Olsen grade 3 actinic keratoses.
- Have been treated for your actinic keratosis with surgery, cryotherapy, laser, radiotherapy, electrosurgery, 5-fluorouracil, diclofenac, imiquimod or retinoids 4 weeks previously.
- Treatment with oral retinoids or nicotinamide in the previous 12 weeks.
- Patients on oral treatment with metformin.
- Patients with severe renal, hepatic and cardiac disease in whom oral metformin is contraindicated.
- Patients with porphyria.
- Patients with systemic diseases that may interfere with the results of the study.
- Patients who are not expected to be able to follow the indications of the study.
- Patients with hypersensitivity to any of the study drugs.
- Immunosuppressed patients.
- Pregnant or breastfeeding women.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Patients will receive treatment for 12 weeks and will be observed for 36 weeks after completion of treatment to assess clinical efficacy and adverse effects.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP10310250 · ATC
- Active substance
- Metformin Embonate
- Substance synonyms
- Metformin hemiembonate, METFORMIN PAMOATE
- Route of administration
- TOPICAL ADMINISTRATION
- Max daily dose
- 2 DF dosage form
- Max total dose
- 168 DF dosage form
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- It is a topical O/W emulsion formulation of metformin
Placebo 1
The placebo components are propylene glycol, neoPCLO/W, fenonip XB and purified water.
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 1
Methyl Aminolevulinate Hydrochloride
SCP193641 · ATC
- Active substance
- Methyl Aminolevulinate Hydrochloride
- Substance synonyms
- (4-METHOXYCARBONYL-2-OXO-BUTYL)AZANIUM CHLORIDE
- Route of administration
- TOPICAL ADMINISTRATION
- Max daily dose
- 1 DF dosage form
- Max total dose
- 1 DF dosage form
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XD03 — METHYL AMINOLEVULINATE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Instituto De Investigacion Sanitaria Aragon
- Sponsor organisation
- Fundacion Instituto De Investigacion Sanitaria Aragon
- Address
- Edificio Ciba, Avenida De San Juan Bosco 13 Avenida De San Juan Bosco 13
- City
- Zaragoza
- Postcode
- 50009
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Instituto De Investigacion Sanitaria Aragon
- Contact name
- Clinical Investigation Unit
Public contact point
- Organisation
- Fundacion Instituto De Investigacion Sanitaria Aragon
- Contact name
- Clinical Investigation Unit
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Authorised, recruitment pending | 135 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitario Miguel Servet
Dermatology, Paseo De Isabel La Catolica 1-3, 50009, Zaragoza
Hospital Universitario Fundacion Alcorcon
Dermatology, Calle Budapest 1, 28922, Alcorcon
Hospital General Universitario De Ciudad Real
Dermatology, Calle Del Obispo Rafael Torija S/n, 13005, Ciudad Real
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 4 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2025-520798-38-00_es | 4 |
| Recruitment arrangements (for publication) | Blank document | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_es | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC metformin_es | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-28 | Spain | Acceptable with conditions 2025-01-30
|
2025-01-30 |