Long-term Safety and Efficacy of Ralinepag in Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      This study was an open-label extension study to determine the long-term safety and
      tolerability of ralinepag in subjects with World Health Organization (WHO) Group 1 pulmonary
      arterial hypertension (PAH) who have completed Study APD811-003, or who were assigned to
      receive placebo and were discontinued due to clinical worsening.
    

Detailed description: 
      This study was an open-label extension study to determine the long-term safety and
      tolerability of ralinepag in subjects with WHO Group 1 PAH who completed Study APD811-003.
      Subjects who completed Study APD811-003 and met eligibility criteria for Study APD811-007
      were enrolled. Additionally, placebo-treated subjects who discontinued study drug treatment
      due to clinical worsening in Study APD811-003 were permitted to enroll in Study APD811-007,
      upon approval of the medical monitor, provided that all end of study procedures including
      right heart catheterization (RHC) were performed per the study protocol. The Week 25 Visit in
      Study APD811-003 served as the Baseline Visit for Study APD811-007.

      All subjects enrolled in Study APD811-007 received open-label treatment with ralinepag. The
      starting dose and titration schedule were individually determined and in accordance with the
      starting dose and titration schedule optimized from Study APD811-003. Adjustments in the dose
      and titration schedule were made according to subject tolerability.

      After an individual subject completed Study APD811-003 and that subject's database was
      locked, subject unblinding occurred. Subjects on active treatment (ralinepag) remained on
      their current dose and had onsite clinical assessments performed every 3 months until the
      subject was discontinued from the study.

      Subjects in the placebo treatment group underwent a dose titration period until a stable,
      maximum tolerated dose (MTD) was reached (up to 9 weeks), followed by a treatment period
      after the MTD was determined during which monthly onsite clinic assessments were performed
      for the first 3 months and then every 3 months until the subject was discontinued from the
      study or the study was terminated. Dose reductions could be made at any time for safety
      reasons. Incremental dose increases were also allowed during the Treatment Period at the
      discretion of the Investigator (as clinically indicated) and according to the stepwise
      titration scheme.

      Subjects were assessed for clinical worsening during each clinic visit. If clinical worsening
      was confirmed, the Investigator could have opted to either continue treatment with ralinepag
      at the current dose, increase the dose of ralinepag, interrupt treatment, or discontinue the
      subject at his/her discretion.

      In addition, attempts were made to contact all subjects at the time of Study APD811-007
      termination to assess their vital (mortality) status. After the last subject enrolled in
      Study APD811-007 completed approximately 6 months of the study, a cumulative all-subject data
      analysis was performed for all subjects who entered the study. Subjects continued to have
      visits to the clinic every 3 months until the Sponsor discontinued the study. At the time of
      the Sponsor's decision to discontinue the study, all ongoing subjects completed an End of
      Study Visit. A 28-day Follow-up Visit was conducted to ensure appropriate subject safety.
      Subjects who remained on ralinepag were eligible to transition into the Phase 3 open-label
      extension study (ROR-PH-303) prior to APD811-007 study termination. For those subjects that
      did not enroll in Study ROR-PH-303, a 28-day Follow-up Visit was conducted to evaluate
      ongoing subject safety, including survival status.
    

Intervention name(s): Ralinepag
Intervention type(s): Drug
Intervention description(s): Active
Other intervention name(s): APD811
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment