Phase 1 Maximal Use Pharmacokinetic Study of Tirbanibulin Ointment 1% in Subjects With Actinic Keratosis.

Tirbanibulin is a novel tubulin polymerization and Src kinase signaling inhibitor. This study was designed to fully characterize tirbanibulin pharmacokinetics (PK) when applied topically under maximal use conditions. This was an open-label, parallel-group PK safety study of tirbanibulin ointment 1% applied to 25 cm2 of the face or balding scalp in adults with actinic keratosis (AK). Eligible subjects self-applied tirbanibulin once-daily for 5 days. PK sampling occurred on days 1, 3 and 4 at 0 hour (before dosing), and on day 5 at prespecified time points up to 24 hours after application. Safety assessments included adverse events and local skin reactions were evaluated up to day 29. Eighteen subjects (face or scalp, n = 9 each) completed the study. Subjects were White (100%), of mean [range] age 66.4 [43-83] years, predominantly men (83.3%) with Fitzpatrick skin type I to III (94.4%); baseline AK lesion count, mean [range] 8.2 [6-14]. All subjects had quantifiable but low plasma concentrations of tirbanibulin. On day 5, overall mean (standard deviation) maximum concentration (Cmax ) was 0.26 (0.23) ng/mL (or 0.60 nM), median time to maximum concentration was 6.91 hours, and mean (standard deviation) area under the plasma concentration-time curve from time 0 to 24 hours was 4.09 (3.15) ng ∙ h/mL. Four subjects experienced a total of 5 treatment-emergent adverse events that resolved. Mild to moderate erythema, flaking, or scaling in the treatment area peaked around day 8 before resolving or returning to baseline by day 29. In conclusion, under maximal use conditions, tirbanibulin ointment 1% for 5 days in the treatment of AK on the face or scalp was well tolerated and resulted in low systemic exposure with subnanomolar plasma concentrations.

Intralesional interferon alpha-2b in the treatment of basal cell carcinoma and squamous cell carcinoma: revisited.

BACKGROUND: Intralesional interferon (IFN) alpha-2b has been shown to be a safe and effective mode of treatment for basal cell carcinoma and squamous cell carcinoma. Multiple studies published in the 1980s through the early 1990s have demonstrated the efficacy of intralesional interferon in the treatment of these malignancies. Unfortunately, this modality appears to be underused. OBJECTIVE: This article serves to remind dermatologists that in addition to cryotherapy, electrodesiccation, and surgical excision, intralesional IFN-alpha is an important part of the armamentarium in the treatment of nonmelanoma skin cancers. METHODS: In addition to a review of the literature, we present eight cases in seven patients successfully treated with intralesional IFN for basal cell carcinoma and squamous cell carcinoma. CONCLUSIONS: Its nonsurgical approach and excellent cosmetic results make IFNalpha-2b an attractive option for patients and an important alternative when other treatment modalities are impractical or contraindicated.

Compared efficacy and safety of tretinoin 0.1% microsphere gel alone and in combination with benzoyl peroxide 6% cleanser for the treatment of acne vulgaris.

Our purpose was to evaluate the efficacy and safety of a combination of benzoyl peroxide 6% cleanser and tretinoin 0.1% microsphere gel versus monotherapy with tretinoin 0.1% microsphere gel. Eighty-seven healthy males and nonpregnant nonlactating females between the ages of 12 and 30 years with moderate inflammatory acne vulgaris were enrolled in this randomized controlled, investigator-blind, parallel group clinical trial. Subjects were evaluated over 12 weeks for a total of 4 visits. The investigators and subjects completed questionnaires about the test medications. Data from the 56 subjects completing the protocol were considered in the analyses of efficacy and tolerability. The reduction in inflammatory lesions from baseline was significant for both treatment groups at the end of the study. However, there was a significantly greater reduction in the group receiving the combination regimen. Both treatment groups had significant reductions from baseline in noninflammatory lesions at week 12, but no differences were observed between treatment groups. With the exception of skin tightness, which was significantly greater at week 12 in the subjects who received the monotherapy, there were no significant differences between the 2 treatment groups with respect to localized irritation. Adverse events were rare in all subjects. Not only did the combination regimen result in a greater reduction of inflammatory acne lesions than use of the monotherapy but also it did not result in an increase in local irritation.