Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral Minocycline for Moderate-to-Severe Acne
October 2017 | Volume 16 | Issue 10 | Original Article | 1022 | Copyright © October 2017
Terry M Jones MD,a Herman Ellman MD,b Tina deVries PhDb
aJ&S Studies, Inc., College Station, TX bFoamix Pharmaceuticals, Inc., Bridgewater, NJ
Abstract
OBJECTIVE: To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne.
METHODS: A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21.
RESULTS: Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation.
CONCLUSION: Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well-tolerated treatment option for individuals with moderate-to-severe acne.
J Drugs Dermatol. 2017;16(10):1022-1028.
INTRODUCTION
Acne vulgaris (AV) is one of the most common skin diseases, affecting 40 to 50 million persons of all ages and races in the United States.1 Most teenagers—approximately 85%—will have acne; however, almost all age groups can be affected and acne can persist into adulthood.2There are many available therapeutic options for AV. They often target key pathogenic factors of acne, including inflammatory activity, follicular hyperkeratinization, Propionibacterium acnes colonization, and sebum production.1,2 Among these therapies, systemic antibiotics have been a mainstay of acne treatment for years. Minocycline and doxycycline, in particular, are recommended by the American Academy of Dermatology as first-line treatment options for moderate-to-severe AV.2 Oral minocycline formulation, for example, is indicated for moderate-to-severe acne and has been shown to be an effective treatment.3 Topical therapy is also an important option in treating dermatologic conditions and for control or cure of the underlying disease.4 Topical antibiotics have been posited to work via both anti-inflammatory and antibacterial action.2 Currently, the recommended topical antibiotics to treat acne are erythromycin and clindamycin.2 No topical tetracycline product is available at this time.A novel topical foam formulation of minocycline (FMX101) was developed to facilitate local application and bioavailability of the drug, while providing the efficacy of minocycline for the treatment of AV with minimum systemic exposure. In a 12-week, Phase 2, prospective and randomized clinical study of 150 subjects with moderate-to-severe AV treated once daily with topical minocycline foam (1% and 4%) or vehicle, there was statistically significant reduction in the number of inflammatory and non-inflammatory lesions from baseline, as well as improvement in the Investigator’s Global Assessment (IGA) score, after 12 weeks of treatment with topical minocycline foam 4% vs vehicle.5 The results of the Phase 2 study showed that topical minocycline foam 4% may be an effective and well-tolerated treatment for moderate-to-severe AV.5
