Once-daily Dapsone 7.5% Gel for the Treatment of Acne Vulgaris in Preadolescent Patients: A Phase IV, Open-label, 12-week Study.

CLINICAL TRIALS ID: NCT02959970 BACKGROUND: Acne vulgaris in patients aged younger than 12 years is increasingly common and primarily noninflammatory (i.e., comedonal). Dapsone 7.5% gel is indicated for the topical treatment of acne vulgaris in patients nine years of age or older. OBJECTIVE: We sought to evaluate efficacy, safety, tolerability, and pharmacokinetics (PK) of once-daily topical dapsone 7.5% gel. METHODS: This was a Phase IV, multicenter, open-label study in patients with acne aged 9 to 11 years. Patients applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. Patients in the PK cohort applied dapsone 7.5% gel under maximal-use conditions for eight days and a thin layer for the remaining 11 weeks. Lesion counts and proportions of patients with an Investigator's Global Assessment score of zero points (clear) or one point (almost clear) were assessed. Plasma concentrations of dapsone and metabolites were evaluated after one week in the PK cohort. Safety and dermal tolerability were evaluated. RESULTS: After 12 weeks, facial acne was clear or almost clear in about 47 percent of patients. Inflammatory, noninflammatory, and total lesions decreased from baseline, with a greater reduction apparent in noninflammatory lesions. Systemic exposure to dapsone in PK patients was low. The overall rate of adverse events was low, and dermal tolerability scores indicated no or mild stinging/burning, dryness, scaling, and erythema. CONCLUSION: Once-daily topical dapsone 7.5% gel used for 12 weeks was safe, effective, and well tolerated in preadolescent patients with acne.

Limited Systemic Exposure with Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis.

BACKGROUND: Glycopyrronium tosylate (GT; Qbrexza® [glycopyrronium] cloth, 2.4%) is a topical anticholinergic approved (USA) for primary axillary hyperhidrosis in patients aged ≥ 9 years. OBJECTIVE: The objective of this study was to compare the pharmacokinetics and safety of GT to oral glycopyrrolate (phase I study) and assess the relationship between glycopyrronium pharmacokinetics and anticholinergic-related adverse events or efficacy with population pharmacokinetics using data from two phase II studies. METHODS: In the phase I study, study staff applied GT to axillae of patients with primary axillary hyperhidrosis (aged 9-65 years) once daily (5 days); oral glycopyrrolate was administered to healthy adults (aged 18-65 years) every 8 hours (15 days). In the phase II studies (NCT02016885 [20 December, 2013], NCT02129660 [2 May, 2014]), adults with primary axillary hyperhidrosis applied topical glycopyrronium (0.8-3.2%) or vehicle to axillae once daily (4 weeks). Pharmacokinetic and adverse event data were collected in all studies. RESULTS: Glycopyrronium pharmacokinetic parameters were similar between adult and pediatric patients treated with GT; there was no evidence of accumulation. Systemic absorption of glycopyrronium was lower with GT vs oral glycopyrrolate. No anticholinergic-related adverse events occurred with GT in the phase I study, while dry mouth and nasal dryness occurred with oral glycopyrrolate; anticholinergic adverse events occurred in the phase II studies. In the population pharmacokinetic analysis, frequency/severity of anticholinergic-related adverse events increased with higher glycopyrronium concentration; no relationship was observed between efficacy and pharmacokinetic measures. CONCLUSIONS: These studies indicate limited absorption of GT compared to oral glycopyrrolate and a low risk of anticholinergic adverse events with proper GT administration when following instructions for use (wipe each underarm once with same cloth, wash hands, avoid ocular contact).

Safety and Tolerability of Sarecycline for the Treatment of Acne Vulgaris: Results from a Phase III, Multicenter, Open-Label Study and a Phase I Phototoxicity Study.

Objective: We sought to evaluate the safety, tolerability, and patterns of use for the once-daily oral, narrow-spectrum antibiotic sarecycline in patients with moderate-to-severe acne vulgaris during a 40-week Phase III, multicenter, open-label extension study. Participants: Patients aged nine years or older with moderate-to-severe acne who completed one of two prior Phase III, double-blind, placebo-controlled, 12-week trials in which they received sarecycline 1.5mg/kg/day or placebo were included. Measurements: The primary assessment was the safety of sarecycline 1.5mg/kg/day for 40 weeks as indicated by adverse events (AEs), vital signs, electrocardiograms, clinical laboratory tests, and physical examinations. Patterns of sarecycline use were a secondary assessment. Results: The safety population included 483 patients; 354 patients (73.3%) completed the study. The most common reasons for premature discontinuation were withdrawal by the patient (14.5%), lost to follow-up (7.9%), and AEs (2.5%). The most common treatment-emergent AEs (TEAEs) were nasopharyngitis (3.7%), upper-respiratory-tract infection (3.3%), headache (2.9%), and nausea (2.1%). Clinical laboratory evaluations suggested no clinically meaningful differences between the treatment sequences. Rates of TEAEs commonly associated with other tetracycline antibiotics include dizziness (0.4%) and sunburn (0.2%), and for gastrointestinal TEAEs, nausea (2.1%), vomiting (1.9%), and diarrhea (1.0%). Also reported herein are the results of a Phase I phototoxicity study. Conclusion: Patients aged nine years or older with moderate-to-severe acne vulgaris who received sarecycline once daily for up to 40 weeks showed low rates of TEAEs, with nasopharyngitis, upper-respiratory-tract infection, headache, and nausea being the only TEAEs reported by 2% or more of patients. No clinically meaningful safety findings were noted. ClinicalTrials.gov Registration: NCT02413346.

Efficacy and Safety of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Oral Doxycycline in Subjects With Severe Inflammatory Acne Who Are Candidates for Oral Isotretinoin.

INTRODUCTION: Acne treatment guidelines suggest a combination approach with topical therapy including a topical retinoid, benzoyl peroxide and an oral antibiotic, or oral isotretinoin (OI), as first-line treatment options for severe acne vulgaris (AV). This study evaluated the efficacy and safety of a daily regimen of 0.3% adapalene and 2.5% benzoyl peroxide (0.3% A/BPO) gel and oral doxycycline 100 mg twice daily in severe (nonnodulocystic, non-conglobate) inflammatory AV. METHODS: This was a phase 4, 12-week, single-arm, openlabel, multi-center investigational study. Subjects (males and females, 12 or older, with severe inflammatory AV, Investigator Global Assessment [IGA] 4, and less than equal to 4 nodulocystic lesions, n=186) were considered OI candidates at baseline by the investigator. OI candidacy was re-evaluated at each study visit. Efficacy endpoints included inflammatory lesion (IL) reduction (week 12), IGA success (defined as IGA 0 [Clear] or 1 [Almost Clear], weeks 4, 8, and 12), percent reduction in lesions (weeks 4, 8, and 12), and subject questionnaires (week 12). Safety assessments included adverse events (AEs) and tolerability. RESULTS: Mean IL counts were significantly reduced from baseline to the end of the study (mean [SD]; baseline, 44.8 (21.73); week 12, 14.8 (16.11); mean percent reduction, 66.2% [30.47]; P less than .0001). By week 12, 37.1% of subjects achieved IGA Success (n=69, P less than .0001). Most subjects self-reported at least moderate improvement in AV (90.2%), and were "Satisfied" or "Very Satisfied" with the study treatment overall (83.2%). 41.9% of the subjects were no longer considered by their investigator to be OI candidates at week 4. At 12 weeks, only 19.9% were still considered OI candidates. CONCLUSION: 0.3% A/BPO + DOX is an effective and safe treatment option for severe inflammatory AV, before starting OI treatment, or as an alternative when OI cannot be used. ClinicalTrials.gov identifier: NCT02899000

J Drugs Dermatol. 2018;17(3):264-273.

Agminated Spitz nevi: report of a child with a unique dermatomal distribution.

Spitz nevi most commonly present as solitary lesions. Multiple agminated Spitz nevi are a rare presentation, with 38 reported cases in the English language literature. We report a 2-year-old girl who presented with multiple Spitz nevi in a unique, dermatome-like distribution and review the English-language literature on agminated Spitz nevi.

Early and explosive development of nodular basal cell carcinoma and multiple keratoacanthomas in psoriasis patients treated with cyclosporine.

The use of cyclosporine to treat psoriasis has been widely adopted since 1997, when the microemulsion form (Neoral) became available. While the causal relationship between cyclosporine and the development of malignant neoplasms has been well described in the transplant literature, it is difficult to apply this relationship to cyclosporine-treated psoriasis, since lower dosages are used (3-5 mg/kg/d vs. 7-15mg/kg/d) for a shorter duration. Current literature suggests that cancer risk is not increased when cyclosporine is used in dermatologic doses for less than 2 years in healthy patients who are not on other immunosuppressants. We report two patients with explosive basal cell carcinoma and keratoacanthoma development, respectively, within 3 months of initiation of cyclosporine. Neither patient had a history of skin cancer, had received PUVA therapy, or was on additional immunosuppressive therapy. To our knowledge, there have been no previous reports of the development of similar lesions in cyclosporine-treated psoriatic patients within such a short timeframe. The results of these patients may herald the need for increased awareness by dermatologists for explosively-growing neoplasms in the setting of cyclosporine-treated psoriasis.