Fig. 2
Study design. Patients with pulmonary arterial hypertension will be assigned to two successive cohorts to receive one dose of RT234 (0.5 mg for cohort 1 and 1.0 mg for cohort 2) via the Dry Powder Inhaler (DPI; Plastiape S.p.A., Osnago, Italy). Screening 6-minute walking tests (6MWT) to determine baseline 6-minute walking distance will be conducted between days − 28 and − 3 of the study (visit 1). On day 1 (visit 2), patients will undergo baseline cardiopulmonary exercise testing (CPET) to measure peak oxygen consumption (VO2). On day 8 (visit 3), patients will receive 0.5 mg (cohort 1) or 1.0 mg (cohort 2) RT234 and will perform CPET 30 minutes post dose. On day 15 (visit 4), patients will receive 0.5 mg (cohort 1) or 1.0 mg (cohort 2) RT234 and will perform the 6MWT 30 minutes post dose. Blood samples will be collected at visits 3 and 4 before RT234 dosing; at 3, 15, and 30 minutes post dose; immediately at the end of the exercise period; and at 45, 75, 120, 180, and 240 minutes post dose for pharmacokinetic (PK) measurements. Patients will be monitored for 240 minutes post dose at visits 3 and 4. Follow-up will be conducted by telephone on day 45 (visit 5). Safety will be monitored throughout the study by the Safety Monitoring Committee (SMC)