This was a multicenter, randomized, double-blind, vehiclecontrolled, clinical study in patients with moderate-to-severe acne who met specific inclusion/exclusion criteria as described below. Protocol received approval from the appropriate institutional review board (IRB) for each center before patient enrollment and were conducted in accordance with the Declaration of Helsinki and Good Clinical Practices (GCP) and in compliance with local regulatory requirements. All patients were informed of the study details and provided written consent.
Patients were enrolled with an Evaluator Global Severity Score [EGSS] score of 3 (moderate) or 4 (severe). Treatments were randomized (2:2:1:1) to tazarotene 0.045% lotion, tazarotene 0.1% cream, and vehicle lotion or cream (to ensure blinding). Data on vehicle are combined in the result presented here. All patients applied study medication to the face once-daily in the evening for 12 weeks; after being instructed to gently washing their face with a non-medicated cleanser.
Approximately 210 patients were planned for enrollment. Eligible patients were of any gender, race and ethnicity aged 12 years and older who presented with 20 to 40 inflammatory lesions (papules, pustules, and nodules), 20 to 100 noninflammatory lesions (open and closed comedones), and two nodules or less. Women of childbearing potential were required to have a negative urine pregnancy test result and to agree to use an effective form of contraception for the duration of the study. A washout period of up to 1 month was required for patients who used previous prescription and over-the-counter acne treatments (and six months for systemic retinoids). Investigator approved non-mediated facial cleanser, moisturizer, and sunscreen was allowed.
Efficacy evaluations comprised inflammatory, and noninflammatory lesion counts and an EGSS at screening, baseline, and during treatment (at weeks 2,4, 8, and 12) performed by the investigator. Primary efficacy endpoints included mean absolute change from baseline to week 12 in inflammatory and noninflammatory lesion counts, and the proportion of patients who achieved at least a 2-grade reduction from baseline to week 12 in EGSS and were ‘clear’ or ‘almost clear’. Other efficacy endpoints included mean percent change from baseline to week 12 in inflammatory and noninflammatory lesion counts. Data for vehicle lotion and cream were pooled for the efficacy analysis.
Additional analyses were performed to evaluate the impact of treatment on other patient outcomes. These included a Patient Satisfaction Survey (PSS) with scores ranging from 1-10 (where 10 was the most satisfied); a validated Acne-Specific Quality of Life (Acne-QoL) questionnaire (Merck & Co, Inc. Whitehouse, NJ); and a Subject Self-Assessment (SSA) scale (using a 7-point scale, where 0=worse and 6=clear). The SSA was assessed at baseline and weeks 2, 4, 8, and 12; PSS and Acne-QoL were completed at baseline and week 12.
Cutaneous safety (erythema, scaling, hypopigmentation, and hyperpigmentation) and tolerability (itching, burning, and stinging) were assessed using a 4-point scale where 0=none, 1=mild, 2=moderate and 3=severe. The investigator assessed erythema, scaling, and hyper-/hypopigmentation at the time of the study visit. Itching, burning, and stinging were solicited from the patient and recorded as an average of the patient’s symptoms during the period since the previous visit.
Safety was also evaluated through reported adverse events (AEs), which were summarized by treatment group, severity, and relationship to study medication.
The intent-to-treat (ITT) population comprised all patients randomized and provided with study drug and vehicle. The safety population comprised all randomized patients who were presumed to have used the study medication or vehicle at least once and who provided at least one post baseline evaluation. The primary method of handling missing efficacy data in the ITT analysis set was last observation carried forward (LOCF). No imputations were made for missing safety data.
Reductions in lesion counts are presented as means and contrast p-values are from a ranked analysis of covariance with factor of treatment and the respective baseline lesion count as covariate. Significance of EGSS reductions were obtained from a Cochran-Mantel-Haenszel (CMH) test.
All statistical analyses were conducted using SAS® version 9.3 or later. Statistical significance was based on 2-tailed tests of the null hypothesis resulting in P values of 0.05 or less.