Efficacy, safety, and pharmacokinetics of inhaled treprostinil in Japanese patients with pulmonary hypertension associated with interstitial lung disease

The INCREASE trial, conducted in the United States, showed that inhaled treprostinil improved exercise capacity in pulmonary hypertension associated with interstitial lung disease (PH-ILD). However, hemodynamic and pharmacokinetic measurements were not performed in the trial. The objective of this trial was to evaluate the efficacy on hemodynamics and exercise capacity, safety, and pharmacokinetics (PK) of inhaled treprostinil in Japanese patients with PH-ILD. This trial was a multicenter, non-randomized, open-label, single-arm trial of patients with PH-ILD. Inhaled treprostinil was administered at 3 breaths (18 μg)/session four times daily, and the dose was gradually increased to a maximum of 12 breaths (72 μg)/session. The primary endpoints were the change of pulmonary vascular resistance index (PVRI) and peak 6-min walking distance (6MWD) from baseline to week 16. Endpoints also included other efficacy parameters, safety, and PK. Twenty patients received inhaled treprostinil. At week 16, PVRI decreased from baseline by −40.1% (95% CI, −53.1 to −27.2) and peak 6MWD increased by 13.0 m (95% CI, −15.0 to 49.0). The most frequently reported adverse events related with treprostinil were cough, malaise and blood pressure decreased. PK was similar to those in pulmonary arterial hypertension (PAH) patients. Treatment with inhaled treprostinil using the same dosing regimen as in the INCREASE trial resulted in improvements in hemodynamics and exercise capacity with a favorable tolerability and safety profile in Japanese patients with PH-ILD.