Question What is the efficacy and safety of clascoterone cream, 1%, in the treatment of facial acne among patients older than 9 years? Findings Results of 2 phase 3 randomized clinical trials including 1440 patients demonstrated that patients with acne treated with clascoterone cream, 1%, experienced greater treatment success vs treatment with vehicle, with considerable reductions in absolute noninflammatory and inflammatory lesion counts. Adverse events with use of clascoterone cream, 1%, were predominantly mild and similar to those with use of vehicle. Meaning Clascoterone cream, 1%, a novel topical androgen receptor inhibitor, appears to demonstrate a favorable safety profile and improvement in efficacy for acne treatment. Importance Acne is a common, multifactorial skin condition, and treatments with novel mechanisms have been elusive. Objective To assess the safety and efficacy of clascoterone cream, 1%, a novel topical androgen receptor inhibitor, in 2 phase 3 randomized clinical trials (CB-03-01/25 and CB-03-01/26). Design, Setting, and Participants Two identical, multicenter, randomized, vehicle-controlled, double-blind, phase 3 studies conducted from November 2015 to April 2018 evaluated the efficacy and safety of use of clascoterone cream, 1%, in males and nonpregnant females 9 years and older with moderate or severe facial acne as scored on the Investigator’s Global Assessment scale. Participants were enrolled if they had 30 to 75 inflammatory lesions and 30 to 100 noninflammatory lesions. Interventions Patients were randomized to treatment with clascoterone cream, 1%, or vehicle cream and applied approximately 1 g to the whole face twice daily for 12 weeks. Main Outcomes and Measures Treatment success was defined as an Investigator’s Global Assessment score of 0 (clear) or 1 (almost clear), and a 2-grade or greater improvement from baseline and absolute change from baseline in noninflammatory and inflammatory lesion counts at week 12. Safety measures included adverse event frequency and severity. Results A total of 1440 patients were randomzied in 2 studies. In CB-03-01/25, 353 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-58] years; 221 [62.6%] female), and 355 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [9-50] years; 215 (60.6%) female); in CB-03-01/26, 369 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-50] years; 243 [65.9%] female), and 363 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [range, 11-42] years; 221 [60.9%] female). At week 12, treatment success rates in CB-03-01/25 and CB-03-01/26 with clascoterone cream, 1%, were 18.4% (point estimate, 2.3; 95% CI, 1.4-3.8; P < .001) and 20.3% (point estimate, 3.7; 95% CI, 2.2-6.3; P < .001) vs 9.0% and 6.5% with vehicle, respectively. At week 12, in both CB-03-01/25 and CB-03-01/26, treatment with clascoterone cream, 1%, resulted in a significant reduction in absolute noninflammatory lesions from baseline to −19.4 (point estimate difference, −6.4; 95% CI, −10.3 to −2.6; P < .001) and −19.4 (point estimate difference, −8.6; 95% CI, −12.3 to −4.9; P < .001) vs −13.0 and −10.8 with vehicle, respectively, as well as a reduction in inflammatory lesions from baseline to −19.3 (point estimate difference, −3.8; 95% CI, −6.4 to −1.3; P < .001) and −20.0 (point estimate difference, −7.4; 95% CI, −9.8 to −5.1; P < .001) vs −15.5 and −12.6 with vehicle, respectively. Adverse events rates were low and mostly mild; the predominant local skin reaction was trace or mild erythema. Conclusions and Relevance Use of clascoterone cream, 1%, for acne treatment appears to demonstrate favorable efficacy and safety with low adverse event rates. Trial Registration ClinicalTrials.gov Identifiers: NCT02608450 and NCT02608476 This review of 2 randomized clinical trials assesses the safety and efficacy of topical clascoterone cream, 1%, a novel androgen receptor inhibitor for acne treatment.
