The main changes implemented with this amendment were: • Changed Screening Period to 30 days. • Added/clarified study assessments for subjects who discontinued study drug before Week 24. • Clarification of collection and/or timing for clinical laboratory tests, height, NT-proBNP, and RHC. • Added that AEs extending beyond the final visit were followed for up to 30 days. • Inclusion criterion revised to require PCWP or LVEDP less than or equal to 15 mmHg. • Exclusion criterion clarified that discontinuation of PDE5-I or ERA could be within 30 days prior to Screening. • To continue to collect endpoint data (Week 24 6MWD) on subjects who added second PAH oral therapy, as well as collect safety data in subjects who were presumably declining during the study but did not meet the protocol definition of clinical worsening. • Removed allowance for subjects that have background PAH therapy removed during treatment to continue into the open-label extension study.

The main changes implemented with this amendment were: • Definition of clinical worsening disease progression and unsatisfactory clinical response criteria revised. • Clarification of collection and/or timing for clinical laboratory test, contraceptive use, ECGs, NT-proBNP, RHC, visit windows, and telephone contact. • Minimum permitted dosage of tadalafil changed to 20 mg once daily if prescribed per the approved prescribing guidelines. • Updated guidelines and definitions for recording AEs to current practice. • The estimated study duration was revised to indicate an overall estimated study duration of 4 years. • Added language to indicate RHC, ECG, chest X-ray, ventilation perfusion scan, high resolution computerized tomography scan, multigated angiogram, pulmonary angiography, and pulmonary function tests may be performed during Screening if required to satisfy inclusion/exclusion criteria.

The main changes implemented with this amendment were: • Dosing was changed from BID to TID and the maximum allowable dose was changed from 15 mg BID to 12 mg TID. • The term Events of Special Interest was removed and replaced by Clinical Worsening Events to ensure consistency in assessing and reporting. • Inclusion criteria revised so that subjects must have received an approved PDE5-I or ERA for at least 30 days, but no more than 1 year before randomization. • New exclusion criterion added for subjects that have chronic renal insufficiency as defined by either a Screening creatinine value >2.5 mg/dL (221 μmol/L) or the requirement for dialysis. • Clarification of collection and/or timing for exercise capacity testing (6MWT and Borg dyspnea score).

The main changes implemented with this amendment were: • Changed PAH background therapy from ERA or PDE5-I to PAH-approved oral monotherapy. Also updated dosing requirements to indicate that dosing of the background therapy must comply with the approved prescribing information for the product. • Clarified the duration of background oral monotherapy for inclusion in the study: initial treatment with any approved PAH therapy occurring no more than 1 year prior to randomization and at a stable dose for a minimum of 10 days prior to randomization. • Dosing of study drug updated so first dose taken at the study site with food (0.125 mg). Dosing was then to continue at 0.125 mg TID with food. Dose escalations could occur no more frequently than every 24 hours. • Allowed temporary use of prostacyclins (28 days or less) for the treatment of clinical worsening and allowed those subjects to transition into the open-label study. • Clarified recording oxygen usage in the CRF when related to the 6MWT. In addition, limitations were placed on use of pulmonary rehabilitation during the study. • Inclusion criteria changed to require RHC within 3 years of Screening, to remove requirement for chest radiograph, and clarify total lung capacity assessments. • Included requirement for subject to complete dosing diary through Week 24. • Method for recording and reporting AEs associated with progression of PAH clarified.

The main changes implemented with this amendment were: • Reduced sample size and number of clinical worsening events based on results from recently completed time to clinical worsening studies. • Removed 1-year time limit on approved PAH background monotherapy. • New exclusion criterion added to reduce the likelihood of enrolling subjects who had clinically relevant left ventricular diastolic dysfunction.

The main changes implemented with this amendment were: • Added optional vital status data collection every 6 months for the duration of the study from subjects who discontinued early from the study.

The main changes implemented with this amendment were: • Increased the sample size/corrected the sample size calculation. • Changed the previous co-primary endpoint of 6MWD at Week 24 to a secondary endpoint. • Added an interim efficacy analysis conducted after 75% of total adjudicated clinical worsening events occurred. • Revised the order of the 3 key secondary endpoints and included a hierarchical approach to analyzing the key secondary endpoints. • Added the secondary endpoint of exercise capacity as assessed by 6MWD measured at each visit up to Week 48 other than Week 24. • Clarified the definition of clinical worsening events and that clinical worsening events were adjudicated. • Addition of an approved pharmacotherapy for PAH. • Clarified RHC could be performed during Screening. • Clarified inclusion/exclusion criterion regarding PAH-approved oral therapies. • Revised when DMC meetings occurred.

The main changes implemented with this amendment were: • Added exploratory objectives for optional evaluation of biomarkers and pharmacogenomics.