The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.

The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, scaling, and plaque thickness/elevation as guidelines. Higher PGA scores represent more severe disease. This scale ranges from 0 to 5, with 0 = best outcome.

The Psoriasis Area and Severity Index (PASI) scoring system combines the assessment of lesion severity and extent of affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, and legs). Each area is assessed for 3 signs: erythema (redness), induration (plaque thickness), and scale. The severity of each sign in each body area is assessed and scored independently using a 5-point scale, where 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. Each area is also assessed for percent of skin involved: 0 = (0%), 1 = (1-<10%), 2 = (10-<30%), 3 = (30-<50%), 4 = (50 -<70%), 5 = (70-<90%), 6 = (90-100%). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. Higher scores indicate more severe disease. PASI is a static assessment made without reference to previous scores.

The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.

Changes in laboratory values, biomarker values, ECG results and vital signs were assessed for clinical relevance.

Safety Analysis Set: All randomized subjects who receive at least 1 application of study drug will be included in the safety analysis set.

At each specified study visit, the Investigator (or qualified evaluator) assessed the presence and overall degree of irritation at the application sites, according to the LTS. The score will ideally represent an 'average' across all application sites. To the fullest extent possible, the same Investigator (or designated evaluator) will perform all tolerability assessments for an individual participant throughout the study.

Safety Analysis Set: All randomized subjects who receive at least 1 application of study drug will be included in the safety analysis set.

The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug.

PK Analysis set: All subjects who have at least 1 application of study drug and have at least 1 evaluable PK assay result will be included in the PK analysis set. The majority of subjects had plasma levels of tapinarof and tapinarof sulfate that were below the level of quantitation (BQL). AUCo-tau value could not be calculated for 17 of the 21 subjects on Day 1 and 18 of the 19 subjects on Day 29, due to BQL samples. The metabolite (tapinarof sulfate) was BQL in all samples.

The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing.

PK Analysis Set: All subjects who have at least 1 application of study drug and have at least 1 evaluable PK assay result will be included in the PK analysis set. No subject had measurable concentrations of the metabolite (tapinarof sulfate) at any time point.

The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.

PK Analysis Set: All subjects who have at least 1 application of study drug and have at least 1 evaluable PK assay result were included in the PK analysis set. No subject had measurable concentrations of the metabolite (tapinarof sulfate) at any time point. An elimination half-life (t½) could not be determined in the majority of subjects (19/21 subjects [90.5%]) on Day 1 and all subjects on Day 29 due to the lack of detectable tapinarof in plasma samples in the elimination phase.

Identify clinically relevant effect of tapinarof on cardiac conduction

QT/QTc analysis set: The QT/QTc analysis set will include all subjects in the safety analysis set with measurements at Baseline as well as on-treatment with at least 1 post-dose time point with a valid ΔQTcF value.

The relationship between tapinarof plasma concentrations and ∆QTcF was investigated using a linear mixed-effects modeling approach with ΔQTcF as the dependent variable. A linear model with an intercept was fitted for tapinarof plasma concentrations, which represented the data in an acceptable way. The slope of tapinarof plasma concentration in the concentration-QTc relationship was estimated.

PK/QTc Analysis Set included all subjects with at least 1 pair of post-dose PK and QTcF data from the same time point.

Of the 21 total subjects, there were 10, 8, 12, 10, 11, 11, 13, and 17 subjects with tapinarof plasma concentrations BLQ at the 1, 2, 3, 4, 5, 8, 12, and 24 hour post-dose time points, respectively. The number of participants with measurable tapinarof ranged from 4 to 13 across all the timepoints. The slope is determined based on the data available for each timepoint.

The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, scaling, and plaque thickness/elevation as guidelines. Higher PGA scores represent more severe disease. This scale ranges from 0 to 5, with 0 = best outcome.

Safety Analysis Set: All randomized subjects who receive at least 1 application of study drug will be included in the safety analysis set.

The Psoriasis Area and Severity Index (PASI) scoring system combines the assessment of lesion severity and extent of affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, and legs). Each area is assessed for 3 signs: erythema (redness), induration (plaque thickness), and scale. The severity of each sign in each body area is assessed and scored independently using a 5-point scale, where 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. Each area is also assessed for percent of skin involved: 0 = (0%), 1 = (1-<10%), 2 = (10-<30%), 3 = (30-<50%), 4 = (50 -<70%), 5 = (70-<90%), 6 = (90-100%). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. Higher scores indicate more severe disease. PASI is a static assessment made without reference to previous scores.

Safety Analysis Set: All randomized subjects who receive at least 1 application of study drug will be included in the safety analysis set.

The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.

Safety Analysis Set: All randomized subjects who receive at least 1 application of study drug will be included in the safety analysis set.