Actinic keratosis MedDRA version: 20.0 Level: PT Classification code 10000614 Term: Actinic keratosis System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Sponsors
Cutanea Life Sciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For enrollment of subjects the following criteria must be met: 1. Male and female subjects =18 years with a condition of general good health (with the exception of AK). The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease other than AK following a detailed medical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, virology and urinalysis; 2. Confirmed clinical AK diagnosis by dermatologist (biopsy proven after end of study, in untreated part of the AK field) 3. At least 2 facial fields of at least 25 cm2 (but preferably >35 cm2) present at screening and baseline visit where more than 2 AK lesions are visible in each field (preferably the forehead, temple or cheek) 4. Able to participate and willing to give written informed consent and to comply with the study restrictions. 5. Ability to communicate well with the investigator in Dutch. 6. Willing to refrain from using other topical products in the treatment area, or prohibited medications for the duration of the study. 7. Willing to limit sun exposure of the involved skin to the extent vocationally possible. 8. Subjects and their partners of childbearing potential must use effective contraception, for the duration of the study and for 3 months after the last dose. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: Eligible subjects must meet none of the following exclusion criteria: 1. Have used or received any treatment for AK in the treatment area within 28 days prior to enrollment (including topical medications, immunosuppressive or immunomodulating agents, phototherapy, oral retinoids, or other therapies for AKs) 2. Have any current pathologically relevant skin conditions in the field area other than AK (e.g. squamous cell carcinoma or basal cell carcinoma). 3. Have a known hypersensitivity to any of the investigational product ingredients, including digoxin and furosemide. 4. Current use of systemic digoxin or furosemide. 5. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year 6. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening or intention to donate blood or blood products during the study. 7. If a woman of childbearing potential, pregnant, or breast-feeding, or planning to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective • To explore the pharmacodynamics of ICVT comprised of digoxin and furosemide (dual agent), digoxin (single agent), furosemide (single agent) in patients with AK. • To evaluate clinical efficacy of ICVT comprised of digoxin and furosemide (dual agent), digoxin (single agent), furosemide (single agent), and vehicle gel. ;Secondary Objective: Secondary Objectives • To evaluate the safety and tolerability of ICVT comprised of digoxin and furosemide (dual agent), digoxin (single agent), furosemide (single agent) ;Primary end point(s): Efficacy and Pharmacodynamic endpoints • Complete clinical clearance (CCC) per field • Change in AK-FAS (AK field assessment scale) • Change in lesion count per field • Investigator global score of each field (IGS, using a 7 point scale from -2 (significantly worse) to +4 (completely cured), according to Nelson et al. 2013) • Evolution of one assigned target lesion in the field, assessed by dermoscopy (assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score) • Standardized photography with Canfield VISIA or 2D photography (depending on the location of the field) • Biopsy biomarkers (where validated assays available at the time of study completion: IFN-a. IFN-g, Ki-67, p53, MCM7 (minichromosome maintenance protein 7), putrescene, spermidine, beta HPV types 5,8,15,20,24,38) • Skin swab markers (where validated assays available at the time of study completion: beta HPV types 5,8,15,20,24,38 by luminex, qPCR for HPV DNA) Tolerability / safety endpoints Adverse events (AE) will be collected throughout the study, at every study visit. Laboratory safety testing, 12-Lead ECGs and vital signs will be performed at screening and EOS. Plasma digoxin levels will be determined by therapeutic drug monitoring (TDM) at the end week 3 (day 21) and 6 (day 42). Patients will fill in a daily questionnaire (numeric rating scale pain/itch) about local tolerance (e-diary) as well as for treatmen | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Centre for Human Drug Research
Outcome results
None listed