The 2 aforementioned phase III clinical trials also found that clascoterone 1% is generally well-tolerated.8,13 Any adverse events that were recorded were mostly mild, with no systemic adverse events or changes in electrocardiograms (ECGs) observed.6 Across both studies, the most common adverse effects reported in patients receiving the medication included local skin irritation such as erythema (occurring in 12.2% of participants using clascoterone vs 15.4% using placebo), scaling or dryness (occurring in 10.5% of participants using clascoterone vs 10.4% using placebo), and pruritus (occurring in 7.7% of participants using clascoterone vs 8.2% using placebo), all of which occurred at similar rates compared with patients who received placebo.8,13
The most common treatment-emergent adverse events (TEAEs) observed were nasopharyngitis (occurring in 1.7% of participants using clascoterone vs 3.7% of participants using placebo in CB-01-03/25, and in 1.1% vs 1.9% in CB-01-03/26), headache (0.6% in clascoterone group vs 0.3% in placebo group in CB-01-03/25 and 1.1% vs 0.8% in CB-01-03/26), oropharyngeal pain (0.6% in clascoterone group vs 0.3% in placebo group in CB-01-03/25 and 1.1% vs 1.1% in CB-01-03/26), and vomiting (0.6% in clascoterone group vs 0.6% in placebo group in CB-01-03/25 and 0.5% vs 0.3% in CB-01-03/26).8 Overall, clascoterone 1% was found to have a similar safety profile compared with the placebo cream.6
At this time clascoterone is only approved for use in patients ages 12 years and above.13 This medication is not mutagenic or carcinogenic.13
To date, no clinical evidence suggests Hypothalamus-Pituitary-Adrenal (HPA) axis suppression by clascoterone.20,21 A 2019 open-label phase II clinical trial studied clascoterone's potential to cause adrenal suppression if used for 2 weeks in 42 subjects ages 12 and older with moderate-to-severe acne vulgaris.22 Primary safety endpoints were defined as HPA axis response to cosyntropin at day 1 compared with day 14, and pharmacokinetic evaluation in the form of concentration-time profiles of clascoterone and cortexolone; secondary safety endpoints included clinical laboratory testing, local and systemic adverse events, physical exams, vital signs, and ECGs.22 This study found that, while 3 out of 42 subjects in the study demonstrated evidence of abnormal HPA axis responses to cosyntropin at the endpoint of day 14, no clinical evidence of adrenal suppression was ever observed.22 Additionally, these 3 subjects all demonstrated normal HPA axis responses 4 weeks after the study’s conclusion.22 Finally, laboratory testing showed that cortexolone plasma concentrations were consistently below the lower limit of quantitation, confirming that no correlation exists between systemic clascoterone exposure and HPA axis suppression.22 Similar to prior study observations, the majority of recorded local skin reactions (LSRs) were mild, with one case of moderate pruritus noted.22 Thus, this phase II clinical trial concluded that clascoterone is safe and tolerable for use.22
One open-label, long-term extension clinical trial has been conducted to evaluate the safety of clascoterone. This clinical study occurred from March 2016 to August 2018, where participants from the phase III clinical studies detailed above had the option to continue applying their assigned study medication (either clascoterone 1% cream or placebo cream) twice daily to the face and/or trunk for up to 9 months.5 The study participants were assessed at 1, 3, 6, and 9 months, and if they were found to have an IGA score of 1 or 0, they entered an off-treatment period until the next study assessment.5 Any patients who planned to use other acne medications, planned to undergo procedures involving the face and/or trunk, or had other skin pathologies that could interfere with the skin assessments were excluded.5 This was a multinational study with 324 subjects participating from 75 sites.5
At the end of 9 months, no systemic adverse events from the medication were observed, and TEAEs occurred at low rates.5 Additionally, TEAEs were found to occur at similar rates between the placebo cream and the clascoterone 1% cream.5 LSRs included erythema,
