TOPICA Pharmaceuticals, Inc., has announced positive results from its Phase 1/2a trial evaluating the safety, tolerability and pharmacokinetics of a 10% solution of luliconazole after maximal use topical application in adults with moderate-to-severe distal subungual onychomycosis of the toenails.
The open-label, single-site study enrolled 24 patients who received once-daily applications of a maximal dose of 10% luliconazole solution in the clinic for 29 days.
Based on subject comments during the trial, follow-on photographs were collected in a subset of subjects for 90 days post-dosing to assess any treatment effect on the nails.
Results showed that all 24 patients enrolled in the study completed the trial at the starting dose, and the 10% luliconazole solution was well tolerated.
In addition, steady state levels of luliconazole were reached in the plasma by day eight due to the time required for the drug to cross the nail plate and nail bed before reaching the circulation.
The steady state plasma levels as seen at day eight in the Phase 1/2a study are consistent from a timing perspective with results of TOPICA's preclinical work, which showed that a substantial amount of 10% luliconazole solution had crossed the nail by day seven in an in vitro human toe nail penetration model.
The plasma levels of luliconazole measured in the Phase 1/2a study were low, suggesting little risk for safety concerns or drug-drug interactions.
Luliconazole was also present in the plasma seven days after the final application, suggesting that the drug continues to pass through the nail and into the circulation, similar to the time course for the drug to initially reach the circulation.
Patients in the trial underwent ECG monitoring as required by the FDA for new molecular entities. No cardiac effects were observed with luliconazole.
"These findings together with the results of follow-on photography showing that some patients experienced notable nail clearing despite having moderate-to-severe onychomycosis and a very short course of treatment suggest that the product has the potential to be an effective and safe topical therapy for onychomycosis that merits further clinical research," said Dr. Terry M. Jones, lead study investigator and dermatologist in College Station, Texas.
To follow the Phase 1/2a study, TOPICA plans to conduct a Phase 2 trial, which will enroll approximately 240 patients with mild-to-moderate distal subungual onychomycosis.
The trial will assess the safety and efficacy of the 10 percent luliconazole solution in two dosing regimens and evaluate the impact of luliconazole on clear nail growth and fungal eradication, which are important clinical endpoints for phase 3 and product approval.
"The 10% luliconazole solution performed as we had predicted based on our in vitro pre-clinical work. Given luliconazole's high potency against fungi causing onychomycosis, our formulation's ability to reach the nail bed and the well tolerated formulation, we believe that the product has the potential to be a highly effective and safe topical therapy for the estimated 35 million adults suffering from onychomycosis in the U.S.," said Greg Vontz, president and chief executive officer of TOPICA.
Vontz continued, "Based on the Phase 1/2a results, we plan to advance clinical development of this product with the initiation of a robust Phase 2 trial in the second half of this year. We are currently raising a Series A round to fund the Phase 2 program."