Safety and Pharmacokinetics of FMX103 (1.5% Minocycline Topical Foam) in Subjects with Moderate-to-Severe Papulopustular Rosacea under Maximum-use Treatment Conditions

Abstract

BACKGROUND: FMX103 1.5% is the first and only topical minocycline foam that is approved for the treatment of papulopustular rosacea in adults. OBJECTIVE: We sought to characterize the safety and pharmacokinetics of minocycline under maximal-use conditions of FMX103 1.5% in subjects with moderate-to-severe rosacea. METHODS: This Phase Isingle-center, nonrandomized, open-label, single-period pharmacokinetics and safety evaluation study evaluated multiple-dose, topical administration of FMX103 1.5%. Twenty subjects meeting study inclusion/exclusion criteria had ~2 grams of FMX103 1.5% applied to the full face once per day for 14 days. Blood samples were collected 30 minutes prior to study drug application on treatment Days 1, 2, 6, 9, 11, 12, and 14, and also at 2, 4, 8, 12, 16, and 24 hours post-administration on treatment Days 1 and 14. RESULTS: Following topical application of a 2-gram maximal-use dose of FMX103 1.5% for 14 days, minocycline plasma concentrations were low. Overall, trough levels were approximately 0.5ng/mL from 24 hours after the first dose through 24 hours after the last dose on Day 14, indicating that steady-state levels appear to have been reached within the first day of dosing. Daily application of FMX103 1.5% was generally safe and well-tolerated by all subjects. CONCLUSION: Once-daily topical application of FMX103 1.5% did not lead to appreciable systemic exposure or accumulation of minocycline, suggesting that it is a viable treatment option for papulopustular rosacea.

Keywords: Minocycline; Phase I study; maximum use; open-label; papulopustular rosacea; pharmacokinetics; topical foam.

FIGURE 1.

Study design; tx end: end of treatment

FIGURE 2.

Plasma concentrations of minocycline on Days 1 and 14 following FMX103 1.5% application LLOQ: lower limit of quantification; SD: standard deviation Note that Day 1 plasma concentrations were collected up to 24 hours post-administration (i.e., up to predose on Day 2)

FIGURE 3.

Trough plasma concentrations of minocycline in subjects treated with FMX103 1.5% LLOQ: lower limit of quantification; SD: standard deviation ^aPredose ^b24 hours postdose ^cThe time of sample collection on Days 2 and 15 is relative to the dose application on Days 1 and 14, respectively.