Long Term Safety and Efficacy of Ralinepag in Pulmonary Arterial Hypertension
Long Term Safety and Efficacy of Ralinepag in Pulmonary Arterial Hypertension
This study is an open-label extension study to determine the long-term safety and
 tolerability of APD811 in patients with WHO Group 1 PAH who have completed the Phase 2 study,
 APD811-003. Patients must have completed the APD811-003 study and must meet eligibility
 criteria for APD811-007.
This study is an open-label extension study to determine the long-term safety and
 tolerability of APD811 in patients with WHO Group 1 PAH who have completed the Phase 2 Study
 APD811-003. Patients must have completed Study APD811-003 and met eligibility criteria for
 Study APD811-007. Additionally, placebo-treated patients who discontinue study drug treatment
 due to clinical worsening in Study APD811-003 will be permitted to enroll in Study
 APD811-007, upon approval of the medical monitor, provided that all end of study procedures
 including right heart catheterization are performed per protocol. The Week 25 Visit in Study
 APD811-003 will serve as the Baseline Visit for Study APD811-007.

 All patients enrolled in Study APD811-007 will receive open-label treatment with APD811. The
 starting dose and titration schedule will be individually determined and in accordance with
 the starting dose and titration schedule optimized from Study APD811-003. Adjustments in the
 dose and titration schedule may be made according to patient tolerability.

 After an individual patient completes Study APD811-003 and that patient's database is locked,
 patient unblinding will occur. Patients on active treatment (APD811) will remain on current
 dose and have onsite clinical assessments performed every 3 months until the patient is
 discontinued from the study.

 Patients in the placebo treatment group will undergo a dose titration period until a stable,
 maximum tolerated dose (MTD) is reached (up to 9 weeks), followed by a treatment period after
 the MTD is determined during which monthly onsite clinic assessments will be performed for
 the first 3 months and then every 3 months until the patient is discontinued from the study
 or the study is terminated (see Table 2).

 Discontinuation of the study may also occur at Sponsor's decision to terminate the study.
 Dose reductions may be made at any time for safety reasons.

 Incremental dose increases will also be allowed during the Treatment Period at the discretion
 of the investigator (as clinically indicated) and according to the stepwise titration scheme.
 Uptitration should not occur within 6 weeks of an efficacy assessment.

 Patients will be assessed for clinical worsening during each clinic visit. If clinical
 worsening is confirmed, the Investigator may opt to either continue treatment with APD811 at
 the current dose, increase the dose of APD811, interrupt treatment, or discontinue the
 patient at his/her discretion.

 In addition, all patients will be contacted yearly following discontinuation in Study
 APD811-007 to assess mortality status. The mortality status follow-up contact of patients who
 withdraw consent will depend on local regulations or specific agreement with the subject and
 investigator.

 After the last patient enrolled in Study APD811-007 has completed approximately 6 months of
 the study, a cumulative all-patient data analysis will be performed for all patients who
 entered the study. Patients will continue to have visits to the clinic every 3 months
 indefinitely to collect data until marketing approval of APD811 is granted or until the
 Sponsor discontinues the study. At the time of marketing approval or the Sponsor's decision
 to discontinue the study, all on-going patients will complete an End of Study Visit. A 28-day
 Follow-up Visit will be conducted to ensure appropriate subject safety.
Inclusion Criteria:

 -  Evidence of a personally signed and dated informed consent document

 -  Is willing and able to comply with scheduled visits, treatment plan, laboratory tests,
 and other study procedures and is deemed an appropriate candidate for participation in
 a long-term extension study and administration of APD811

 -  Fulfilled all eligibility criteria for APD811-003 and completed the study as
 planned

 -  Patients who discontinued for clinical worsening in APD811-003 and were assigned
 to placebo and completed all end of study procedures including right heart
 catheterization (RHC) may participate after their data from the APD811-003 study
 is cleaned and locked

 Exclusion Criteria:

 -  Patients who enrolled in APD811-003 and were withdrawn from study drug treatment due
 to any AE, SAE, or clinical worsening if assigned to APD811, or patients who did not
 complete the APD811 003 study for other reasons.

 -  Female patients who wish to become pregnant

 -  Systolic BP <90 mmHg at Baseline/Day 1

 -  Other severe acute or chronic medical or laboratory abnormality that may increase the
 risk associated with study participation or investigational product administration or
 may interfere with the interpretation of study results and, in the judgment of the
 investigator, would make the patient inappropriate for entry into this study