Journal of drugs in dermatology : JDD · 2022
Dermal Safety of Tapinarof Cream 1%: Results From 4 Phase 1 Trials.
Клиническое исследование I фазыСтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Jett John, McLaughlin Michael, Wilson Timothy, Somerville Matthew, DellaMaestra Wayne, Rubenstein David, Piscitelli Stephen
Аннотация
BACKGROUND: Tapinarof (VTAMA®; Dermavant Sciences, Inc.) is a novel, non-steroidal, topical, aryl hydrocarbon receptor agonist, FDA approved for psoriasis treatment and under investigation for atopic dermatitis treatment as a 1% cream formulation for once-daily (QD) application.
OBJECTIVE: Evaluate cumulative skin irritation, sensitization, and photoallergic and phototoxic potential of tapinarof cream 1% across a range of dosing frequencies and conditions.
METHODS: We conducted 4 randomized, controlled, phase 1 trials of topical tapinarof cream 1% vs vehicle or other appropriate controls in healthy adults. Cumulative skin irritation was assessed following QD application for 21 days under fully occlusive patch conditions. Contact sensitization, photoallergenicity, and phototoxicity were assessed under semi-occlusive patch conditions. The contact sensitization and photoallergenicity trials used an induction phase of repeated applications followed by a 2-week rest period and a 1-time challenge, with rechallenge if responses indicated sensitization/photosensitization; the phototoxicity trial comprised a single application. Ultraviolet A and B irradiation was used to assess photoallergenicity/toxicity.
RESULTS: 376 participants were randomized across the 4 trials. In the cumulative irritation trial, tapinarof cream 1% QD was classified as having a slight potential for very mild cumulative irritation under the exaggerated test conditions of repeated dosing for 21 days. There was no evidence of sensitization, photosensitization, or phototoxicity. Tapinarof was well tolerated and there was a low discontinuation rate across all trials.
CONCLUSIONS: Tapinarof cream 1% was well tolerated, non-sensitizing, non-phototoxic, and non-photoallergic, with no evidence of clinically meaningful cumulative skin irritation in 4 dermal safety trials in healthy adults.
TRIAL REGISTRATION: IND 104601 J Drugs Dermatol. 2022;21(10):1084-1090. doi:10.36849/JDD.6627R1.
OBJECTIVE: Evaluate cumulative skin irritation, sensitization, and photoallergic and phototoxic potential of tapinarof cream 1% across a range of dosing frequencies and conditions.
METHODS: We conducted 4 randomized, controlled, phase 1 trials of topical tapinarof cream 1% vs vehicle or other appropriate controls in healthy adults. Cumulative skin irritation was assessed following QD application for 21 days under fully occlusive patch conditions. Contact sensitization, photoallergenicity, and phototoxicity were assessed under semi-occlusive patch conditions. The contact sensitization and photoallergenicity trials used an induction phase of repeated applications followed by a 2-week rest period and a 1-time challenge, with rechallenge if responses indicated sensitization/photosensitization; the phototoxicity trial comprised a single application. Ultraviolet A and B irradiation was used to assess photoallergenicity/toxicity.
RESULTS: 376 participants were randomized across the 4 trials. In the cumulative irritation trial, tapinarof cream 1% QD was classified as having a slight potential for very mild cumulative irritation under the exaggerated test conditions of repeated dosing for 21 days. There was no evidence of sensitization, photosensitization, or phototoxicity. Tapinarof was well tolerated and there was a low discontinuation rate across all trials.
CONCLUSIONS: Tapinarof cream 1% was well tolerated, non-sensitizing, non-phototoxic, and non-photoallergic, with no evidence of clinically meaningful cumulative skin irritation in 4 dermal safety trials in healthy adults.
TRIAL REGISTRATION: IND 104601 J Drugs Dermatol. 2022;21(10):1084-1090. doi:10.36849/JDD.6627R1.