Treatment Patients were randomized 1:1 to receive sarecycline (1.5 mg/ kg) or placebo tablets administered orally once daily as 60 mg, 100 mg, or 150 mg of sarecycline or matching placebo tablets for 12 weeks.Efficacy Assessments At baseline and each study visit, facial acne was evaluated using the IGA and inflammatory and noninflammatory lesion counts. IGA scores ranged from 0 (clear) to 4 (severe) and reflected the investigator’s overall general assessment of the quantity and quality of inflammatory lesions. Counts of inflammatory lesions (papules, pustules, and nodules) and noninflammatory lesions (open and closed comedones) on the forehead, cheeks, nose, and chin were recorded at each visit. Acne severity on the back and chest also was evaluated using IGA scores.Efficacy analyses included IGA success for facial acne at week 12, defined as a ≥ 2-point decrease (improvement) from baseline and a score of 0 (clear) or 1 (almost clear), percentage change from baseline in facial inflammatory lesion counts at week 12, and absolute change from baseline in facial noninflammatory lesion counts at week 12. A post hoc analysis to determine the percentage change from baseline in noninflammatory lesion counts was also performed for each study in ITT patients who had ≥10 noninflammatory lesions at baseline. The percentages of patients in the ITT population with IGA success for back and chest acne (defined as a ≥2-point improvement in IGA score in those areas following a baseline IGA score ≥ 2) at week 12 were also assessed as post hoc analyses.Patient-Reported Outcome Measure The Skindex-16, a 16-item questionnaire measuring effects of skin disease on patients’ quality of life using 3 scales (symptoms, emotions, and functioning), with scores standardized from 0 (never bothered) to 100 (always bothered),10 was administered to patients at baseline and week 12.Safety and Tolerability Assessments Treatment-emergent adverse events (TEAEs) were assessed at every visit. Vital signs were recorded at screening, baseline, and each study visit. Clinical laboratory evaluations were conducted at screening, baseline, week 3, and week 12 visits. Electrocardiograms (ECGs) were conducted at screening and at week 12 visits, and physical examinations were conducted at screening, baseline, and week 12 visits.Statistical Analyses Efficacy analyses were conducted in the ITT populations. IGA success at week 12 was calculated using the Cochran-Mantel-Haenszel test, with adjustment for pooled site. The same methodology was used for nonfacial (chest and back) IGA assessments (≥ 2-point decrease in patients with IGA score ≥ 2 at baseline). An analysis of covariance model (ANCOVA), with baseline value as a covariate, treatment and pooled site effects as factors, and significance level set at P less than 0.05, was used to calculate mean percentage changes from baseline in inflammatory lesion counts. This ANCOVA model was also used to calculate mean absolute changes from baseline in noninflammatory lesion counts in the entire ITT population and mean absolute and percentage changes from baseline in noninflammatory lesion counts in patients with ≥ 10 baseline noninflammatory lesions. Missing data were handled using a multiple imputation approach, except for nonfacial IGA assessments, which used observed data.
