Safety and Tolerability of Inhaled Treprostinil in Adult PH Due to COPD

Inclusion Criteria:

1. Diagnosis of WHO Group 3 PH associated with COPD

2. Subjects are required to have a right heart catheterization (RHC) within one yearprior to the first dose of study drug with the following parameters:

3. Pulmonary vascular resistance (PVR) ≥ 4 Wood Units (WU) and

4. A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedgepressure (PCWP) of ≤ 12 mmHg if PVR ≥ 4 WU to < 6.25 WU or ≤ 15 mmHg if PVR ≥ 6.25 WU and

5. A mean pulmonary arterial pressure (mPAP) of ≥ 30 mmHg

6. Clinical Diagnosis of COPD will be made using accepted Global Initiative for ChronicObstructive Lung Disease (GOLD) diagnostic criteria, including Baseline spirometrywith the following documented parameters:

7. FEV1 < 65% predicted, and

8. FEV1/ FVC < 70

9. Baseline 6MWD ≥ 100 meters

Exclusion criteria:

1. The subject has a diagnosis of pulmonary arterial hypertension (PAH) or PH for reasonsother than COPD as outlined in inclusion criterion 3. This would include, but is notlimited to, the concomitant presence of thromboembolic disease (acute or chronic),untreated or inadequately treated obstructive sleep apnea, connective tissue disease (including but not limited to systemic sclerosis/scleroderma, or systemic lupuserythematosus), sarcoidosis, interstitial lung disease,human immunodeficiency virus-1infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications.

2. The subject has received any Food and Drug Administration (FDA)-approved medicationfor the treatment of PAH (ie, prostacyclin, prostacyclin receptor agonist, endothelinreceptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I],or solubleguanylate cyclase [sGC] stimulator) within 60 days of the first dose of study drug,except for acute vasoreactivity testing.

3. The subject has evidence of clinically significant left-sided heart disease as definedby the following criteria per the most recent assessment:

4. Left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedgepressure (PCWP) >15 mmHg (or >12 mmHg if pulmonary vascular resistance [PVR] ≥4to <6.25 WU)

5. Left ventricular ejection fraction <40% as assessed by either angiography orechocardiography.