New Polymeric Once-Daily Tazarotene 0.045% Lotion Formulation for Moderate-to-Severe Acne: Pooled Phase 3 Pediatric Analysis

June 2020 | Volume 19 | Issue 6 | Original Article | 602 | Copyright © June 2020

Published online May 8, 2020

Lawrence F. Eichenfield MD,ª Emil A. Tanghetti MD,b Eric Guenin PharmD PhD MPH,c Gina Martin MOT,d Radhakrishnan Pillai PhDd

ªDepartments of Dermatology and Pediatrics; University of California, San Diego School of Medicine and Rady Children's Hospital, San Diego, CA bCenter for Dermatology and Laser Surgery, Sacramento, CA cOrtho Dermatologics*, Bridgewater, NJ dBausch Health US, LLC*, Petaluma, CA *Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc. Ortho Dermatologics is a division of Bausch Health US, LLC.

To address the continued unmet need for an effective topical acne treatment with improved tolerability, a new tazarotene 0.045% lotion formulation utilizing polymeric emulsion technology was developed. The active ingredient and hydrating and moisturizing ingredients form an oil-in-water emulsion structured by a three-dimensional mesh matrix, ensuring rapid, even, and simultaneous release of ingredients.17 In addition to being aesthetically pleasing, optimized active ingredient delivery with this formulation allows for a lower dose of active dermatological products in an easily applied, highly spreadable formulation. The simultaneous application of a low-dose tazarotene with emollients may also enhance tolerability and improve treatment compliance.

A phase 2 study comparing tazarotene 0.045% lotion with commercially available tazarotene 0.1% cream showed that tazarotene 0.045% lotion was more numerically effective than the higher concentration tazarotene 0.1% cream with fewer treatment-related adverse events (TEAEs).18 In addition, two subsequent, identical phase 3 double-blind, randomized, vehicle- controlled 12-week studies showed tazarotene 0.045% lotion was efficacious versus vehicle and well tolerated in patients with moderate-to-severe acne.19 The objective of this post hoc analysis was to evaluate safety and efficacy of tazarotene 0.045% lotion in pre-adolescent and adolescent patients (10-13 and 14-17 years of age, respectively) with moderate-to-severe acne using pooled data from the two phase 3 trials.


Study Design and Patients
Data were pooled from two identical multicenter, double-blind, randomized, vehicle-controlled, parallel-group phase 3 studies (NCT03168334 and NCT03168321), details of which have been published.19 Briefly, patients aged ≥9 years with Evaluator's Global Severity Scores (EGSS) indicating moderate (3) or severe (4) acne were eligible to enroll at 89 study centers. Eligible participants also had to have had 20-50 facial inflammatory lesions (papules, pustules, and nodules), 25-100 noninflammatory lesions (closed and open comedones), and two or less facial nodules. Patients were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion, applied to the face once daily for 12 weeks. All studies were conducted in accordance with the Declaration of Helsinki, International Conference on Harmonization, Good Clinical Practice Guidelines, and local regulations. All patients or their legal guardians provided written informed consent. The studies were approved by relevant institutional review boards or independent ethics committees at each study center.

Efficacy Evaluation
Efficacy evaluations included inflammatory and noninflammatory lesion counts and treatment success, defined as the proportion of patients achieving ≥2-grade reduction from baseline in EGSS and a score of “clear” (0) or “almost clear” (1). Assessments were performed at screening, baseline, and weeks 2, 4, 8, and 12 (end of treatment). Separately, and independent of investigator assessments, patients completed an Acne Specific Quality of Life (Acne-QoL) questionnaire at baseline (prior to study drug application) and week 12. The validated Acne-QoL questionnaire comprises 19 questions divided into four different domains—self-perception, role-emotional, role-social, and acne symptoms. Questions within each domain are scored from 0 (extremely) to 6 (not at all), with higher scores indicating improved health-related QoL; domain scores range from 0-30 for self-perception, role-emotional, and acne symptoms and 0-24 for role-social.20

Safety Evaluation
Cutaneous safety (scaling, erythema, hypopigmentation, hyperpigmentation) was evaluated by investigators at each post-screening visit using a 4-point scale where 0=none and 3=severe. Patient assessments of tolerability (itching, burning, stinging) were reported at all post-screening visits using the same 4-point scale. Safety was also evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs) throughout the study.

Statistical Analysis
In the individual phase 3 trials, co-primary efficacy endpoints were the absolute reductions from baseline to week 12 in inflammatory and noninflammatory lesion counts and the percentage of patients achieving treatment success at week 12. Secondary efficacy endpoints included percent change in inflammatory and noninflammatory lesion count from baseline to week 12. Patients who were randomized and received study drug comprised the intent-to-treat (ITT) population. The safety population consisted of all randomized patients who used study medication or vehicle at least once with a minimum of one post-baseline evaluation.

For this pooled post hoc analysis, patients were grouped into one of two age groups (pre-adolescent: 10-13 years; adolescent: 14-17 years). Although patients aged ≥9 years were eligible for enrollment, no patients aged <10 years were enrolled in either study. Analyses included the percentage of patients achieving treatment success at week 12, percent change from baseline in inflammatory and noninflammatory lesion counts by visit, and absolute change from baseline to week 12 in the four Acne QoL domains. In the pooled analysis, significant skewness was observed for mean percent changes from baseline in inflammatory and noninflammatory lesions; therefore, a nonparametric method was used in which data were rank transformed prior to the analysis of covariance (ANCOVA), with factor of treatment and the respective baseline lesion count as a covariate. For the comparison of percent changes in lesions counts between age groups, a ranked ANCOVA with factor of age group and respective baseline lesion count as a covariate was utilized. Treatment