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.
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
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