View Abstract

A5688 - A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Subjects with Pulmonary Hypertension Due to Parenchymal Lung Disease (Study RIN-PH-201)
Author Block: A. B. Waxman1, V. F. Tapson2, P. M. Smith3, C. Deng4, S. D. Nathan5; 1Center for Pulmonary Heart Disease, Brigham and Woman's Hosp, Boston, MA, United States, 2Pulmonary, Cedars-Sinai, West Hollywood, CA, United States, 3United Therapeutics, Research Triangle Park, NC, United States, 4United Therapeutics, Durham, NC, United States, 5Inova Fairfax Hosp, Falls Church, VA, United States.
RATIONALE: Pulmonary hypertension (PH) due to lung diseases and/or hypoxemia is classified by the World Health Organization (WHO) as WHO Group 3 PH. This classification includes PH due to interstitial lung disease (ILD) as well as combined pulmonary fibrosis and emphysema (CPFE). PH occurs in up to 80% of these patients and there are currently no approved treatments for PH in patients with ILD or CPFE. Inhaled treprostinil has shown clinical improvements in exercise capacity after 12 weeks of therapy in patients with WHO Group 1 PH and directly targets the more ventilated portion of the lungs in patients with WHO Group 3 PH, minimizing the risk of ventilation perfusion mismatch, which may allow for improvements in exercise capacity. METHODS: The INCREASE study (RIN-PH-201) is a multicenter, randomized (1:1 inhaled treprostinil:placebo), double-blinded, placebo-controlled trial to evaluate the safety and efficacy of inhaled treprostinil in subjects with PH associated with ILD including CPFE. The study will include about 314 patients at approximately 120 clinical trial centers. The treatment phase of the study will last approximately 16 weeks. The primary efficacy endpoint of the study is the change in 6-minute walk distance (6MWD) at Week 16. Additional key assessments during the study include change in peak 6MWD at Week 12, trough 6MWD at Week 15, and change in plasma concentration of N-terminal probrain natriuretic peptide (NT-proBNP). Exploratory assessments will evaluate changes in 6MWD at other time points during the study, Quality of Life as measured by the St George’s Respiratory Questionnaire, time to clinical worsening, and distance saturation product. Optional blood samples for evaluation of biomarkers and pharmacogenomics will also be drawn in subjects providing consent.Patient safety will be evaluated throughout the study by capturing adverse events, hospitalizations, oxygenation (pulse oximetry and supplemental oxygen use), pulmonary function tests, and clinical laboratory parameters. Patients who complete all required assessments will be eligible to enter an open-label, extension study (RIN-PH-202).
RESULTS: Enrollment is ongoing at approximately 120 sites in the United States and is anticipated to continue through 2018 or until all 314 subjects have been enrolled into the double-blind phase of the trial.
CONCLUSIONS: INCREASE will assess whether inhaled treprostinil will improve exercise capacity as measured by 6MWD and other clinical outcomes in subjects with PH associated with ILD including CPFE.