- Verona Pharma confirms today announces the successful completion of the second phase of a Multiple Ascending Dose (MAD) study in which nebulised RPL554, a novel dual PDE3/PDE4 inhibitor, was administered to healthy subjects for up to five consecutive days at doses up to 16x larger than the previously used active dose.

RPL554 is currently in development as a nebulised treatment for acute exacerbations in COPD patients in a hospital or home-care setting. The nebulised bronchodilator market was worth about $1 billion in 2014 in the US1.

The completed MAD study showed that the drug was well tolerated across all dose levels and no maximum tolerated dose was reached.

As found in the interim results from the single ascending dose (SAD) part of this trial, repeat dosing with the new formulation resulted in a longer residence time for RPL554 in the lung and slower release into the blood stream, suggesting that twice daily dosing may be appropriate.

The Company also announces the commencement of a multiple ascending dose study in up to 30 moderate chronic obstructive pulmonary disease (COPD) patients, where each dose will be given for five consecutive days.

The primary objective here is to further confirm the safety and tolerability seen in earlier parts of the trial, as well as to investigate bronchodilation in these COPD patients.

This study is the final part of a Phase I/II clinical trial with RPL554, using a new proprietary nebulised formulation.

The dose range, for both MAD studies, is based on the successfully completed SAD part of this trial in which nebulised RPL554 was delivered at doses up to 16x that previously shown to produce bronchodilation.

As noted in Verona Pharma's press release on 23 March 2015, RPL554, in this study in 50 healthy volunteers, was well-tolerated and was without effect on cardio-vascular parameters and without nausea or vomiting at any dose.

The trial is being performed at the Medicines Evaluation Unit in Manchester by lead investigator Professor Dave Singh.

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