A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle-Controlled Clinical Study to Compare the Safety and Efficacy of a Novel Tazarotene 0.045% Lotion and Tazarotene 0.1% Cream in the Treatment of Moderate-to-Severe Acne Vulgaris

June 2019 | Volume 18 | Issue 6 | Original Article | 542 | Copyright © June 2019


Emil A. Tanghetti MD,a Leon H. Kircik MD,b Lawrence J. Green MD,c Eric Guenin PharmD PhD,d Susan Harris MS,e Gina Martin MOT,f Radhakrishnan Pillai PhDf

aCenter for Dermatology and Laser Surgery, Sacramento, CA bIndiana University School of Medicine, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, Icahn School of Medicine at Mount Sinai, New York, NY cDepartment of Dermatology, George Washington University School of Medicine, Washington, DC dOrtho Dermatologics, Bridgewater, NJ eBausch Health, Bridgewater, NJ fBausch Health Americas, Inc., Petaluma, CA

Safety
A higher proportion of patients treated with tazarotene 0.1% cream (26.8%) reported treatment-emergent AEs compared with tazarotene 0.045% lotion (14.7%) or combined vehicle (13.4%). TEAEs were mostly mild or moderate and unrelated to study drug (Table 2). Treatment-related AEs were more common with tazarotene 0.1% cream. There were two reports of application site pain (2.9%) with tazarotene 0.045% lotion; compared with three reports with tazarotene 0.1% cream (4.2%).

Cutaneous Safety and Tolerability
Each of the signs and symptoms of cutaneous safety and tolerability (scaling, erythema, hypopigmentation, hyperpigmentation, itching, burning, and stinging) showed improvements from baseline to week 12. There were slight increases in mean scores for scaling, burning and stinging at week 4, consistent with tazarotene’s safety profile, but these reduced at subsequent study visits. All mean scores were ≤0.6 (where a score of 1=mild); scores being similar or slightly lower at interim study visits with tazarotene 0.045% lotion compared with tazarotene 0.1% cream, especially in terms of scaling, itching, burning, and stinging at weeks 2 and 4.

DISCUSSION

Despite recommendations to use retinoids as first-line acne treatment,11,21 they remain underutilized.22,24The slow onset of action in the treatment of inflammatory lesions,25 and the widely recognized irritation potential of these agents have somewhat limited their use. Consequently, several attempts have been made to alleviate these efficacy and tolerability issue using new delivery technology. The clinical benefits observed with tazarotene 0.1% foam,26,27 0.1% cream,28 and 0.1% gel29 appear similar, although no direct comparisons exist in the literature.

The rationale behind the development of a novel lotion formulation of tazarotene stemmed from its proven efficacy in acne and the fact that a lotion formulation is the easiest and most acceptable formulation for application to the face; but also the potential for tazarotene cream (and to a lesser extent foam26) to cause concentration dependent skin irritation and dryness, which had been shown to be both bothersome in many patients and may impact adherence and successful acne treatment. For example, pooled results from several clinical studies showed that 14% of patients treated with tazarotene 0.1% foam reported irritation and 7% dryness, compared with only 1% using vehicle.30

Tazarotene 0.045% lotion is a novel topical treatment for moderate- to-severe acne leveraging polymeric emulsion technology with the aim to improve both efficacy and tolerability. The polymeric emulsion technology affords more uniform deposition of active, excipients and moisturizers onto the skin surface. This phase 2 study is the first to compare a novel formulation of tazarotene 0.045% lotion with commercially available taz-arotene 0.1% cream in patients with moderate-to-severe acne. Tazarotene 0.045% lotion was significantly superior to vehicle in reducing both inflammatory and noninflammatory lesions; and numerically more effective than tazarotene 0.1% cream despite the two-fold difference in tazarotene concentration. Median reductions in inflammatory and noninflammatory lesions with tazarotene 0.045% lotion were 72% and 63%, respectively, at 12 weeks.

The only treatment-related AE with tazarotene 0.045% lotion observed was application site pain (2.9%). Skin reactions (such as scaling, burning, and stinging) were infrequent, had onsets early in the treatment period, were mostly mild and appeared transient. Erythema and itching noted at baseline improved progressively with daily tazarotene 0.045% lotion treatment. Again, these data concur with those in other clinical trials of retinoids where the peak of cutaneous irritation typically occurs within the first 1-2 weeks and subsides.31

CONCLUSIONS

Tazarotene 0.045% lotion was developed using a polymeric emulsion technology. In this phase 2 study of patients with moderate- to-severe acne, tazarotene 0.045% lotion was as effective as the higher concentration tazarotene 0.1% cream, with fewer treatment-emergent adverse events.

DISCLOSURES

Drs Tanghetti, Kircik and Green were study investigators. Dr Kircik and Green are advisors to Ortho Dermatologics. Dr Guenin, Pillai, and Ms Harris and Martin are employees of Bausch Health Americas, Inc.

ACKNOWLEDGMENT

The authors acknowledge Brian Bulley, MSc, of Konic Limited for medical writing support. Ortho Dermatologics funded Konic’s activities pertaining to this manuscript.

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AUTHOR CORRESPONDENCE

Emil Tanghetti MD et@dermatologyandlasersurgery.com
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