Safety and Efficacy of APD811 in Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: APD811; Placebo
Intervention description: Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females aged 18-75 years, inclusive

          -  Symptomatic WHO Group 1 PAH classified by one of the following subgroups:

               -  Idiopathic pulmonary arterial hypertension (IPAH);

               -  Heritable pulmonary arterial hypertension (HPAH);

               -  Drugs and toxins induced;

               -  Associated pulmonary arterial hypertension (APAH); specifically connective tissue
                  diseases, HIV infection and congenital heart disease.

          -  Has had the diagnosis of PAH confirmed by cardiac catheterization

          -  Has WHO/NYHA functional class II- IV symptomatology

          -  Previously diagnosed with PAH and on stable oral disease-specific PAH therapy with
             either an ERA and/or an agent acting on the nitric oxide pathway, i.e. a PDE5
             inhibitor or a soluble guanylate cyclase stimulator. Stable is defined as no change in
             dose within 3 months of the start of Screening and for the duration of the study

          -  Has 6MWT distances of 100-500 m, and within 15% of each other on 2 consecutive tests
             done on different days at Screening

          -  Has pulmonary function tests (PFTs) within 6 months prior to the start of Screening
             with no evidence of significant parenchymal lung disease

          -  Has a ventilation-perfusion (V/Q) lung scan or pulmonary angiogram within 5 years
             prior to Screening and concomitant with or following diagnosis of PAH that shows no
             evidence of thromboembolic disease

          -  If on vasodilators (including calcium channel blockers), digoxin, spironolactone, or
             L-Arginine supplementation; the patient must be on a stable dose for at least 1 month
             prior to the start of Screening

        Exclusion Criteria:

          -  Newly diagnosed with PAH and on no disease-specific PAH therapy

          -  Previous participation in any clinical study with an investigational drug, biologic,
             or device within 2 months prior to the Screening visit

          -  Acutely decompensated heart failure within 1 month prior to start of Screening

          -  Systolic blood pressure <90 mm Hg at Screening

          -  Evidence or history of left-sided heart disease and/or clinically significant cardiac
             disease

          -  Use or chronic administration (defined as >30 days) of a prostacyclin or prostacyclin
             analogue within 3 months of Screening

          -  Any previous use of a prostacyclin or prostacyclin analogue that was stopped for
             safety or tolerability issues associated with pharmacology/mechanism of action

          -  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