MATERIALS AND METHODS
Study Design and Patients
The Phase 3 trial designs were described previously (Figure 1).3,7-9 Briefly, patients 9 years of age or older with moderate-to-severe acne vulgaris were randomized to twice-daily treatment of the face with clascoterone cream 1% or vehicle for 12 weeks; patients completing either pivotal study could enter a long-term extension (LTE) study in which all patients applied clascoterone cream 1% twice daily to the face and, if designated by the investigator and desired by the patient, truncal acne for up to 9 additional months.3,7 Patients who achieved an Investigator's Global Assessment (IGA) score of 0 or 1 (IGA 0/1) could stop treatment and resume if/when acne worsened (IGA 2 or greater), as assessed by the investigator for each respective treatment area. Only patients aged 12 years or older were included in the current analysis. The institutional review board or ethics committee approved the study protocols at each participating site. The studies were conducted in accordance with the principles of the Declaration of Helsinki, the current Good Clinical Practice guidelines as defined by the International Conference on Harmonization, and all applicable regulatory requirements. All patients provided written informed consent before participation in the trials. Patients under 18 years of age were accompanied by a parent or legal guardian at the time of consent signing.3,7
Assessments and Outcomes
The IGA was assessed at baseline and every 4 weeks in the pivotal studies and at extension days 0 (pivotal study week 12 visit), 29, 85, 183, and 274 in the LTE study using a 5-point scale (0 = clear to 4 = severe). Efficacy was assessed from the proportion of patients achieving treatment success (defined as IGA of 0 or 1 with a 2-point reduction or greater in IGA score from baseline), assessed separately for the face and trunk in the long-term study. Noninflammatory (NILC), inflammatory (ILC), and total lesion counts (TLC) were obtained at each pivotal study visit, and the absolute and percent changes from baseline in NILC, ILC, and TLC were assessed through week 12.
Statistical Analysis
All statistical analyses were performed using SAS® for Windows, version 9.3 (SAS Institute, Cary, NC). The ITT patient population included all randomized individuals and was used for the analyses. For demographics, baseline characteristics, compliance, and efficacy analyses, continuous variables were described using descriptive statistics and categorical data by frequency counts and proportion of patients within each category. Efficacy comparisons between clascoterone and vehicle were performed using a logistic regression model as described previously.3 Unadjusted and adjusted proportions and least squares means with associated 95% confidence intervals (CI) were analyzed, and two-sided P-values were reported. In the pivotal trials, missing data were handled using a multiple imputation method.3 Missing data were not imputed in the LTE study.
