The first-in-human, double-blind, randomised, placebo-controlled trial is designed to evaluate the safety, tolerability and pharmacokinetics (PK) of oral single ascending doses (SAD) and multiple ascending doses (MAD) of EDP-235.
Both SAD and MAD cohorts of the trial enrolled eight subjects, categorised into a 3:1 ratio to receive EDP-235 or placebo for seven days.
To streamline the selection of EDP-235 dosage, the trial analysed several single and multiple doses in fasted and fed states.
According to the trial results, favourable safety, tolerability and PK were reported.
Robust exposure multiples over the EC₉₀ were observed in the trial with 200mg and 400mg doses of EDP-235.
Furthermore, a dosage of up to 400mg of EDP-235 was generally safe and well-tolerated in healthy participants for up to seven days.
Exposure of EDP-235 rose almost proportionally with increasing single and multiple doses, with a uniform half-life of 13 to 22 hours, offering a PK profile that suits once-a-day dosing.
A rise in exposure was reported with food administration of a standard meal.
These data support the progression of the oral antiviral into a Phase II trial of once-daily dosage without requiring ritonavir.
Following a review by the US Food and Drug Administration, the company plans to begin the Phase II trial of 200mg and 400mg once-daily dose of EDP-235 in the fourth quarter of this year.
A coronavirus 3CL protease inhibitor, EDP-235, can be administered once-a-day treatment for Covid-19.
Enanta Pharmaceuticals president and CEO Jay Luly said: “We are very pleased with the encouraging results from our Phase I study of EDP-235 showing that it was generally safe and well-tolerated up to a once-daily dose of 400mg, which provided plasma drug levels that were six-fold and 12-fold over the plasma protein adjusted EC90 for the Alpha variant and the Delta variant, respectively.
“Moreover, EDP-235 is projected to have four times higher drug levels in lung tissue compared to plasma, which would drive exposure multiples to 24-fold and 48-fold for the respective variants.”
In February this year, the company dosed the first participant in the Phase I trial of EDP-235 for Covid-19.