groups also achieved statistically significant changes in ILC and NILC compared with the placebo group (P=0.0431 and P=0.0303, respectively). Participants using clascoterone 1% BID achieved the highest treatment success rate and greatest decrease in ILC (-13.5) and NILC (-17.5) compared with placebo.19
Two identical phase III clinical trials have been completed for clascoterone so far, named CB-03-01/25 and CB-03-01/26 (NCT02608450 and NCT02608476 on ClinicalTrials.gov).6 Occurring from November 2015 to April 2018, they were both multicenter, randomized, double-blind, vehicle-controlled, parallel-group studies that assessed the safety and efficacy of clascoterone 1% topical cream in males and non-pregnant females ages 9 and up with moderate to severe facial acne.6,13 Eligible participants had an IGA score of 3 or 4, 30 to 75 inflammatory lesions, and 30 to 100 noninflammatory lesions.6 Overall, 1,440 patients participated in the study and applied 1 g of either clascoterone 1% or placebo cream to the whole face daily for a treatment period of 12 weeks.6 Patients were not permitted to use any other topical or systemic acne medications for the duration of the study.6
There were 3 coprimary efficacy endpoints assessed in this hierarchical order: the proportion of patients achieving treatment success at week 12, the absolute change from NILC at week 12, and the absolute change from baseline in ILC at week 12.6 Treatment success was defined as achievement of an IGA score of 0 or 1, or an improvement in IGA score by 2 or more, or an absolute change in lesion counts from baseline.6 The secondary endpoints for the studies were the percentage change from baseline in total lesion count (TLC), NILC, and
ILC at week 12, as well as the absolute change in TLC from baseline at week 12.6
Overall, both phase III clinical trials found clascoterone 1% to be more effective than placebo cream at treating facial acne when applied twice daily for 12 weeks (P<0.001): a significantly greater number of patients receiving clascoterone 1% reached treatment success at week 12 compared with those using placebo cream in both phase III trials (18.4% vs 9.0%, P<0.001 in CB-03-01/25 and 20.3% vs 6.5%, P<0.001 in CB-03-01/26).6 Study participants using clascoterone 1% also achieved a significantly greater absolute reduction in noninflammatory lesion count compared with participants using the placebo cream (-19.4 vs -13.0, P<0.001 in CB-03-01/25 and -19.4 vs -10.8, P<0.001 in CB-03/01/26), as well as a significantly greater absolute reduction in inflammatory lesion count compared with placebo (-19.3 vs -15.5, P=0.003 in CB-03-01/25 and -20.0 vs -12.6, P<0.001 in CB-03-01/26).6
Secondary endpoints were also met because participants using clascoterone 1% achieved significantly greater absolute change in TLC from baseline to week 12 compared with participants using placebo cream (-39.1 vs -28.8, P<0.001 in CB-03-01/25 and -40.0 vs -23.6, P<0.001 in CB-03-01/26), as well as a significantly greater percentage change in NILC, ILC, and TLC compared with participants using placebo (NILC: -30.6% vs -21.6%, P=0.009 in CB-03-01/25 and -29.3% vs -15.6%, P<0.001 in CB-03-01/26. ILC: -44.8% vs -36.5%, P=0.005 in CB-03-01/25 and -46.9% vs -29.6%, P<0.001 in CB-03-01/26. TLC: -37.0 vs -28.4%, P=0.001 in CB-03-01/25 and -37.3% vs -22.1%, P<0.001 in CB-03-01/26).6
Some limitations of these clinical trials were that the sample sizes were small and did not permit subgroup analyses.6 Additionally, these clinical trials did not include patient-reported outcomes as an outcome variable to evaluate the medication's impact on quality of life, and did not test clascoterone’s efficacy when used with concomitant acne treatments.6
Safety
Clascoterone has been shown to have a similar safety profile to that of placebo cream in clinical studies.6 In a prior phase I trial, all adverse events documented during the study were mild or moderate at most.18 In phase II clinical trial, all concentrations of clascoterone at 0.1% BID, 0.5% BID, and 1% BID were well tolerated; the majority of documented adverse events were mild in severity and resolved by the end of the study.19
