Comparative Bioavailability of DFD-29 (Minocycline Hydrochloride Modified Release Capsules, 40 mg) Vs. Minocycline Hydrochloride Extended Release 105-mg tablets After a Single Oral Dose: A Randomized, 3-way Crossover Study

Abstract

Background: A low-dose formulation (DFD-29) of minocycline hydrochloride (HCl) is under evaluation for the treatment of moderate-to-severe papulopustular rosacea. The objective of this phase 1 study is to compare the bioavailability of DFD-29 to that of the currently available Solodyn® (minocycline HCl extended release) 105-mg formulation. Methods: This single-center, randomized, open-label, laboratory-blinded, 3-way, 6-sequence crossover study compared the pharmacokinetics of a single dose of DFD-29 40 mg after an overnight fast, DFD-29 40 mg after a high-fat meal, and minocycline HCl extended release 105-mg tablet (minocycline HCl ER 105 mg) after an overnight fast in healthy adult volunteers. Blood samples were collected for PK assessments prior to and up to 72 hours after each drug dose, with a washout period of 7 calendar days between doses. Safety was evaluated by monitoring adverse events (AEs), vital signs, and laboratory tests. Results: A total of 24 subjects were randomized and 23 subjects completed the study. Mean plasma minocycline Cmax levels were 243.9 ng/mL for DFD-29 (fasting), 225.0 ng/mL for DFD-29 (fed), and 497.3 ng/mL for minocycline HCl ER 105 mg (fasting). The geometric least squares (LS) mean ratios for Cmax, AUC0-T, and AUC0-∞ of DFD-29 to minocycline HCl ER 105 mg when administered after fasting were 47.97%, 36.55%, and 38.35%, respectively. When comparing fasting vs fed administration of DFD-29, geometric LS mean ratios for Cmax, AUC0-T, and AUC0-∞ were 97.48%, 116.84%, and 115.26% respectively. Tmax was 1.5 h for DFD-29 (fasting), 4.5 h for DFD-29 (fed), and 4.0 h for minocycline HCl ER 105 mg (fasting). Treatment-emergent AEs (TEAEs) were reported in 17.4%, 13.0%, and 21.7% after administration of DFD-29 (fasting), DFD-29 (fed), and minocycline HCl ER 105 mg, respectively. Most TEAEs were mild in severity (21/22; 95.5%). Conclusion: Bioavailability was significantly lower after a single dose of DFD-29 40 mg vs minocycline HCl ER 105 mg following a single dose under fasting and fed conditions. Food intake had no impact on Cmax but may delay absorption and may slightly increase exposure. Overall, single oral doses of DFD-29 40 mg and minocycline HCl ER 105 mg were generally safe and well tolerated. This study and abstract are funded by Journey Medical Corporation.