Safety and Efficacy of APD811 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: 
      The study was conducted as a placebo-controlled, randomized, 22-week double-blind study which
      included a dose titration period. An additional transition period occurred for those patients
      who elected to enroll into the open-label extension study, APD811-007. A total of 61 patients
      with PAH were enrolled.
    

Detailed description: 
      Study APD811-003 was a 22-week, randomized, double-blind, parallel-group, placebo-controlled
      study in subjects with symptomatic WHO Group 1 PAH. The study consisted of a dose titration
      period of up to 9 weeks, a 13-week maintenance period, and a follow-up visit that was to
      occur approximately 3 weeks after the end of the maintenance period (Week 25). The transition
      period of 3 weeks (±1 week) was to occur for those subjects who elected to enroll into the
      open-label extension (OLE) Study APD811-007.

      Approximately 60 subjects with PAH were planned to be enrolled (61 actual). After screening,
      eligible subjects were randomized 2:1 to ralinepag (APD811) or to placebo. Randomization was
      stratified by baseline WHO/NYHA functional class (II versus III or IV). Subjects randomized
      to active therapy were given ralinepag at a starting dose of 0.01 mg BID. Subjects randomized
      to the placebo arm received matching placebo capsules to preserve the blind. Subjects were
      instructed to take the study drug (ralinepag or placebo) with food. Dosage was then
      uptitrated, as tolerated, over the course of the 9-week dose-titration period to a maximum
      dose of 0.3 mg BID. Although doses could be reduced based on tolerability, the final dosage
      reached was required to be stable during the 13-week treatment period prior to evaluation at
      Week 22.

      Subjects could receive concomitant oral disease-specific PAH therapy consisting of an ERA
      and/or an agent acting on the nitric oxide pathway, a PDE-5 inhibitor or a sGC stimulator,
      provided the dose had remained stable for at least 3 months prior to the start of screening.
      It was recommended that subjects continue the same dose and regimen of these medications for
      the duration of the study. With the exception of prostanoids, the use of other supporting
      therapies, which may affect PAH, was also permitted.

      During the study, assessments of efficacy were performed including PVR and other hemodynamic
      parameters as determined by RHC, the 6MWT, assessment of clinical worsening, BNP and
      NT-proBNP levels, WHO/NYHA functional class assessment of PAH. Safety assessments included
      standard evaluations of AEs, clinical laboratory values, vital signs, and ECG measurements.

      At the end of the maintenance period, subjects who did not choose to participate in the OLE
      study were to discontinue study drug (ralinepag or placebo). All subjects that chose to
      continue in the OLE study were to remain on study drug until the follow-up visit at Week 25.
      This visit served as the baseline visit for the OLE study if the subject was eligible and
      chose to participate.
    

Intervention name(s): APD811; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Placebo
Other intervention name(s): Ralinepag
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment