Dermal and Systemic Pharmacokinetics of Oral DFD-29 (minocycline hydrochloride modified release capsules, 40 mg) vs Oral Doxycycline 40 mg in Healthy Subjects

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Dermal and Systemic Pharmacokinetics of Oral DFD-29 (minocycline hydrochloride modified release capsules, 40 mg) vs Oral Doxycycline 40 mg in Healthy Subjects Adelaide A. Hebert, MD,1 Srinivas Sidgiddi, MD2 1UTHealth Houston McGovern Medical School, Houston, TX; 2Journey Medical Corporation, Scottsdale, AZ Introduction: A modified-release, low-dose formulation (DFD-29) of minocycline hydrochloride (HCl) is under investigation for the treatment of rosacea. This Phase 1 study compared the dermal and systemic pharmacokinetics of DFD-29 (minocycline HCl, 40 mg) and doxycycline 40 mg in healthy, adult subjects. Methods: This randomized, open-label, single-center, parallel-group study evaluated the systemic and dermal pharmacokinetics of once-daily administration of oral DFD-29 40 mg capsules or oral doxycycline 40 mg for 21 days in healthy adult volunteers. On Day 1, subjects received the assigned study drug under fasting conditions. Blood was sampled before drug administration, every 30 minutes for 4 hours, hourly for 4 hours, and 12 and 24 hours post dose. Dermal interstitial fluid (ISF) was sampled using three open-flow microperfusion probes before dosing, hourly for 8 hours, and at 11-12, 15-16, and 23-24 hours post dose. After discharge, subjects continued to take assigned study drug once daily through Day 21, when they returned to the center and underwent the same procedures as on Day 1. Safety was evaluated by monitoring adverse events (AEs), vital signs, and laboratory tests. Results: A total of 24 subjects were randomized and completed the study. On Day 1, mean plasma Cmax levels with DFD-29 (382.8 ng/mL) and doxycycline (405.9 ng/mL) were comparable (Pr > 0.716). By Day 21, mean plasma Cmax had nearly doubled with doxycycline but remained constant with DFD-29 (701.9 vs 337.7 ng/mL; Pr > 0.037). Mean plasma AUC was also significantly greater with doxycycline than with DFD-29 at Day 21 (6074.8 ng.hr/mL vs 3957.6 ng.hr/mL, Pr > 0.013). In contrast, mean dermal Cmax concentrations were numerically higher with DFD-29 (40 mg) than doxycycline at Day 1 (109.7 vs 81.5 ng/mL; Pr > 0.117) and Day 21 (125.7 vs 114.7 ng/mL; Pr > 0.681). The mean dermal AUC at Day 1 also was greater with DFD-29 than with doxycycline (1412.29 ng.hr/mL Vs 1088.55 ng.hr/mL, Pr > 0.213), and at Day 21 it was similar in the two groups (1604.77 ng.hr/mL for DFD-29 and 1573.63 ng.hr/mL for doxycycline, Pr > 0.954). Both DFD-29 and doxycycline 40 mg were well tolerated by the healthy volunteers. Conclusion: Minocycline from DFD-29 with its modified-release formulation provides higher dermal concentration than doxycycline from Day 1 onwards at a similar dose. The higher concentration from Day 1 at the site of action is expected to translate into a clinically meaningful impact in the treatment of patients with rosacea. This study and abstract are funded by Journey Medical Corporation.