Rezolute has reported that its investigational oral plasma kallikrein inhibitor (PKI), RZ402, was found to be safe and well-tolerated in treating diabetic macular oedema (DME) patients in a Phase Ia clinical study.

A selective PKI, RZ402 is being advanced as an oral, chronic treatment for DME.

Named ‘RZ402-101’, the single centre, randomised, double-blind, placebo-controlled, single ascending dose (SAD) Phase Ia trial assessed the safety profile and pharmacokinetics of single oral doses of RZ402.

It enrolled 30 healthy adults into three cohorts of 25mg, 100mg and 250mg dose levels. In each of these cohorts, the participants were randomised as per an 8:2 ratio to be given either RZ402 or a placebo.

On receiving single doses, subjects stayed in the clinic for seven days to undergo serial pharmacokinetic and safety analyses and were assessed during follow-up visits on days 14 and 30.

Trial results showed that a single oral dose of RZ402 generated plasma concentrations that were considerably over the target pharmacologically active treatment levels.

Furthermore, single doses of RZ402 offered dose-dependent surges in systemic exposure. The therapeutic was safe and well-tolerated at all the tested dose levels, with no dose-limiting toxicities.

This data supports the possible use of once-daily dose of RZ402, and its progress into Phase II.

Rezolute senior vice-president and Clinical Development head Brian Roberts said: “Given that DME is a consequence of diseased microvascular at the back of the eye, we believe that systemic exposure may be crucial in treating the disease.

“It is noteworthy that a single oral dose of RZ402 safely, durably, and substantially exceeded target blood concentrations that have been shown in animal models of DME to reduce retinal inflammation and fluid leakage, the physiological hallmarks of this microvascular disease.”

Rezolute intends to commence a Phase Ib multiple ascending dose study in the third quarter of this year.