Evaluation of the skin sensitization, photoirritation, and photoallergic potential of ingenol mebutate gel in healthy volunteers

Abstract

Objectives: Phase 1 studies were conducted to determine the sensitization (PEP005-005; NCT00357916; https://ichgcp.net/clinical-trials-registry/NCT00357916), photoirritation (PEP005-023; NCT00850811; https://ichgcp.net/clinical-trials-registry/NCT00850811?term=PEP005-023&rank=1), and photoallergic (photosensitizing) potential (PEP005-024; NCT00850681; https://ichgcp.net/clinical-trials-registry/NCT00850681?term=PEP005-024&rank=1) of ingenol mebutate gel 0.01% versus vehicle on normal skin.

Design, setting, participants, and measurements: Healthy volunteers were enrolled in single-center, randomized, controlled, within-subject comparison trials. PEP005-005 was designed as a repeat-insult patch test study. In PEP005-023, treatment areas were examined after irradiation for photoirritation potential; dermal reactions were evaluated. In PEP005-024, irradiation was performed to determine the photoallergic (photosensitizing) potential of the medication. All treatment areas were graded immediately prior to irradiation and 24, 48, and 72 hours following irradiation. In all studies, local tolerability was assessed visually using an ordinal scoring system at set intervals before and after medication application/irradiation.

Results: In PEP005-005 (n=238), a significant difference (p<0.001) was seen between ingenol mebutate and vehicle for mean and total cumulative irritation scores. In PEP005-023 (n=34), mild erythema in all irradiated treatment areas was as expected for the ultraviolet dose. There was no clinically significant irritation in response to ingenol mebutate or vehicle, irrespective of irradiation. In PEP005-024 (n=60), there was no significant irritation in response to either ingenol mebutate or vehicle at their irradiated treatment areas.

Conclusion: RESULTS from three pharmacology studies in healthy volunteers indicate a favorable topical safety profile for ingenol mebutate gel, with no evidence seen of skin sensitization, photoirritation, or photoallergic potential.

Figures

Figures 1A-C

Subject disposition: (a) PEP005-005 (sensitization potential); (b) PEP005-023 (photoirritation potential); (c) PEP005-024 (photoallergic potential)