Pharmacokinetics, Safety and Efficacy of BIA 5-1058 in PAH (Zamicastat)

This is an open-label, multi-centre study in patients with PAH who are currently on stable treatment with at least one PAH medication. It is planned to evaluate the PK profile (24 hour profile and trough levels) and the safety, tolerability and efficacy of four different zamicastat doses. Each patient will start treatment with the lowest dose (50 mg zamicastat once daily) and the dose will be up-titrated to the individual highest tolerated dose (HTD) i.e. up to 200 mg zamicastat once daily. A data safety monitoring board (DSMB) will periodically review the safety data and will issue a recommendation if the doses can be used as planned. This study will consist of: * A screening period, 5 to 12 days: visit V1 * Up to four dose finding periods, 14 days each: * Dose A (50 mg zamicastat once daily): visits A1, A2 and A3 * Dose B (100 mg zamicastat once daily): visits B2 and B3 * Dose C (150 mg zamicastat once daily): visits C2 and C3 * Dose D (200 mg zamicastat once daily): visits D2 and D3 * Maintenance period, 42 days: maintenance period visit (MPV)1, MPV2 and MPV3 * Follow-up (FU) period, 14 to 28 days: visits FU (down-titration) and FU