A Repeat Open Application Patch Test (ROAT) of a new formulation of Dithranol in Healthy Volunteers
Research type
Research Study
Full title
A Repeat Open Application Patch Test (ROAT) using a New Controlled Release Formulation of Dithranol (Dithranol/ProSilic®) Cream in Healthy Volunteer Subjects, preceded by a Preliminary Safety Phase
IRAS ID
1005742
Contact name
David Fleet
Contact email
Sponsor organisation
Soterios Ltd
Eudract number
2022-001272-34
ISRCTN Number
ISRCTN84166928
Research summary
Research Summary
In order to address the factors associated with poor tolerability and compliance of administration of current preparations, the investigational medicinal product (IMP) will be a controlled release, cream based, formulation combining dithranol with ProSilic (a fully biodegradable hybrid of porous elemental silicon (Si14), lipids and amino acids). The silicon atoms are ‘activated’ (electrically charged) to enable a controllable ‘honeycomb’ pore structure as a drug delivery mechanism with the potential to offer enhanced targeting and release characteristics.
The main purpose of the study is to look at whether a new controlled release formulation of dithranol (ProSilic®) has a beneficial effect on the skin irritation and skin staining potential that is seen with normal dithranol cream.
The study will comprise an initial open, prolonged exposure study (“safety phase”) to inform safety for the repeated application study (“repeated phase”). The safety phase is designed to determine the skin irritancy of each of the four topical formulations in healthy volunteer subjects, compared to the Base Formulation (with no dithranol) and E45 Dermatological Cream. The study will involve a progressive patch test with increasing duration of exposure of up to eight hours with follow up assessments at 24, 48 and 72 hours. This approach is designed to minimise the exposure risk for the subjects. Such an approach has been used previously to determine the irritancy of chemicals classified as irritants with no risk to subjects. The repeat phase will be a double-blind, randomised study of the same set of creams, which will be applied to the lower back area of subjects. The creams will be applied to the test sites for periods of 1 hour on seven consecutive days with assessments at Days 1-13 and Day 16. Any clinical signs of cutaneous irritation (or any other clinical signs) will be recorded.
Summary of Results
Protocol SOT03: A repeat open application patch test (ROAT) using a new controlled release formulation of dithranol (dithranol/ProSilic®) cream in healthy volunteer subjects, preceded by a preliminary safety phase.
Safety Phase
Purpose of the study: To measure irritation and staining of dithranol in a new base ProSilic cream (STS01) applied on one day.
What was tested: Four strengths of dithranol/ProSilic (0.25%, 0.5%, 1% and 2%) were compared with the base cream and with E45 cream. Each cream was applied to patches of skin on the body for 1, 2, 4 or 8 hours.
People taking part: 29 healthy adults aged between 21 and 69 years. 20 subjects were female and 9 subjects were male.
Results: There were no important differences between the active cream strengths in the amount of skin irritation measured. Redness occurred in most subjects after application of all active concentrations of the ProSilic (0.25%, 0.5%, 1% and 2%) cream, the reactions being mostly strong and lasting until the latest assessment after 3 days.
Safety: There were no side effects that were considered related to the study creams.
Repeat Phase
Purpose of the study: To measure irritation and staining of dithranol in a new base ProSilic cream (STS01) applied once daily for 7 days.
What was tested: Four strengths of dithranol/ProSilic (0.25%, 0.5%, 1% and 2%) were compared with the base cream and with E45 cream. Each cream was applied to patches of skin on the body for 1 hour per day for 7 days.
People taking part: 30 healthy adults aged between 18 and 70 years. 24 subjects were female and 6 subjects were male.
Results: There were no important differences between the active cream strengths in the amount of skin redness or irritation measured. Skin redness was seen with all strengths of active STS01 cream at some point during the study but was uncommon with the base cream or E45 cream. Most cases of skin redness were seen by the 3rd day of application. Five subjects stopped having some strengths applied because of strong but temporary reactions to the active cream. Overall, there was little or no difference between the active cream strengths and redness or irritation.
Safety: There were no side effects that were considered related to the study creams.REC name
Wales REC 1
REC reference
22/WA/0151
Date of REC Opinion
11 Jul 2022
REC opinion
Further Information Favourable Opinion