Patients with papulopustular rosacea (PPR) treated with DFD-29 40 mg—a minocycline extended-release oral capsule—showed a significantly greater efficacy in response than those administered placebo, DFD-29 20 mg, or doxycycline 40 mg, according to study findings published in Journal of Clinical and Aesthetic Dermatology.
A single-center, open-label study analyzed the utility of DFD-29 extended-release 20 mg and 40 mg capsules in the treatment of patients with PPR. A total of 24 patients (aged 18 to 45 years), were randomly assigned DFD-29 40 mg, DFD-29 20 mg, or doxycycline modified-release 40 mg, once daily for 21 days under fasting conditions. Plasma samples were taken during a 24-hour period on days 1 and 21 for pharmacokinetic (PK) analysis.
On day 1, mean plasma levels showed similar plasma levels in the patient groups treated with DFD-29 40 mg and doxycycline 40 mg, and with DFD-29 20 mg levels about half of those seen with DFD-29 40 mg treatment. At day 21 plasma doxycycline exposure had increased from 4377.5 ng.h/mL to 6074.8 ng.h/mL. It was noted that DFD-29 kept relatively stable minocycline levels throughout the 21 days of daily dosing (DFD-29 40 mg, day 1=3549.6 ng.h/mL and DFD-29 40 mg, day 21=3957.6 ng.h/mL). Results suggested to the investigators that DFD-29 plasma levels do not exceed the predicted antimicrobial threshold and thus indicate a reduced possibility of causing resistance.
The 16-week, multicenter, double blind Phase 2 study included patients aged 18 years and older; inclusion criteria was an Investigator’s Global Assessment (IGA) grade 2-4 (mild-severe), 10 to 40 facial inflammatory legions (papules and pustules; 2 nodules or fewer), and a Clinician’s Erythema Assessment score of 5 to 20 which would indicate moderate to severe erythema. Patients received either DFD-29 40 mg, DFD-29 20 mg, doxycycline 40 mg, or a placebo once daily for 16 weeks.
Treatment with DFD-29 40 mg achieved significant IGA success as compared with the placebo at week 16 (66.04% vs. 11.54%). DFD-29 40 mg also displayed a significantly greater IGA treatment success compared with both doxycycline 40 mg and DFD-29 20 mg. DFD-29 40 mg was shown to be more effective at reducing legions compared with the placebo, DFD-29 20 mg, and doxycycline 40 mg treatment. Furthermore, in multiple clinical trials, doxycycline 40 mg has been tested on patients with moderate to severe PPR and the reduction in legions count was consistently 10 to 14 legions after 16 weeks. DFD-29 40 mg treatment resulted in an average reduction of 19 papules and pustules over the same length of time, or “significantly more” than that achieved with doxycycline, the researchers wrote.
Study limitations cited by the investigators include that the minimum inhibitory concentration (MIC) values and plasma concentrations for antibacterial threshold data are mean values; patients who are fast absorbers or slow metabolizers could exceed the threshold, causing resistance selection pressure.
Based on the data from the studies, the researchers concluded that, “DFD-29 40 mg provided superior efficacy to placebo and doxycycline 40 mg in improving outcomes in papulopustular rosacea. PK assessment indicated that DFD-29 has a low risk of antimicrobial activity, maintaining levels below the predicted MIC threshold.”
Tsianakas A, Pieber T, Baldwin H, et al. Minocycline extended-release comparison with doxycycline for the treatment of rosacea.J Clin Aesthet Dermatol. December 2021, 14 (12):16-23.