A Dose Response Study of UT-15C SR in Patients With Exercise-Induced Pulmonary Hypertension
Condition: Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Hypertension
Intervention: UT-15C
Intervention description: oral
Intervention MeSH terms: Treprostinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a prospective, randomized, parallel group study to assess the hemodynamic effect of
      three different dose regimens of a sustained release (SR) tablet of UT-15C in patients with
      exercise-induced pulmonary hypertension (PH), as measured by the change in peak total
      pulmonary resistance index (TPRI) during exercise from Baseline to Week 12.
    

Eligibility criteria:

        Inclusion Criteria-

        A subject was eligible for inclusion in this study if all of the following criteria
        applied:

          1. Was between the ages of 18 and 75 years of age at Screening

          2. Weighed a minimum of 40 kilograms with a body mass index less than 40 kg/m2 at
             Screening

          3. Agreed to have right heart catheterization with exercise performed at Baseline and
             Week 12, or at the time of early discontinuation of study drug

          4. Had exercise-induced PH at Baseline (defined as a PAPm ≥ 30 mmHg during exercise).

             Note: eligible subjects may or may not have had a PAPm ≥ 25 mmHg at rest

          5. Exercise-induced PH may have been:

               1. Idiopathic, heritable, drug- or toxin-induced PAH, or PAH associated with
                  connective tissue diseases or HIV infection

               2. Due to ILD

               3. Due to sarcoidosis

          6. Had a Baseline pulmonary function tests as follows:

               1. Forced vital capacity (FVC) ≥ 50% (predicted)

               2. If FVC <50% (predicted), total lung capacity (TLC) must be ≥ 50% (predicted)

               3. Forced expiratory volume / forced vital capacity (FEV / FVC) ratio ≥ 50%

          7. Had a Baseline 6MWD between 150 and 450 meters, inclusive

          8. Was optimally treated with conventional pulmonary hypertension therapy (e.g. oral
             vasodilators, oxygen, digoxin, etc) with no additions, discontinuations, or dose
             changes for at least 14 days prior to Baseline (excluding anticoagulants). Oral
             diuretics may have been adjusted, but not discontinued or added, within 14 days of
             Baseline

          9. May or may not have been receiving an approved PDE-5 inhibitor OR an approved ERA.

             Subjects receiving an approved ERA or an approved PDE-5 inhibitor must have been on a
             stable dose for 30 days prior to Baseline, and were willing to remain on a PDE-5
             inhibitor or an ERA and at the same dose for the duration of the 12-week Treatment
             Phase. If a subject chose to discontinue their PDE-5 or ERA prior to entering this
             study, they must have had a ≥30 day washout period between the last dose of the PDE-5
             or ERA and start of the screening phase.

         10. If female, was physiologically incapable of childbearing or practicing an acceptable
             method of birth control as deemed appropriate by the physician or institution. Women
             of childbearing potential had a negative serum pregnancy test at Screening

         11. Was able to communicate effectively with study personnel, and considered reliable,
             willing and likely to be cooperative with protocol requirements, including attending
             all study visits, in the opinion of the Principal Investigator

         12. Voluntarily gave informed consent to participate in the study.

        Exclusion Criteria-

        A subject was not eligible for inclusion in this study if any of the following criteria
        applied:

          1. Had received epoprostenol, treprostinil, iloprost, beraprost, or any other
             prostacyclin therapy within 30 days of Baseline (except if used during acute
             vasoreactivity testing)

          2. Had previous intolerance or significant lack of efficacy to an oral or parenteral
             prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to
             effectively titrate that therapy

          3. Had a concurrent injury, illness (other than PH or a PH related condition), or other
             confounding factor that would prevent the accurate assessment of the subject's
             exercise capacity

          4. Had a musculoskeletal disorder (e.g. recent hip replacement, artificial leg, etc.) or
             any other disease that was likely to limit ambulation, or was connected to a machine
             that was not portable

          5. Had portal hypertension

          6. Had congenital heart disease (repaired or unrepaired)

          7. Had a history or current evidence of left-sided heart disease including myocardial
             infarction in the previous 3 years or mitral valve stenosis, or evidence of current
             left-sided heart disease as defined by mean resting pulmonary capillary wedge pressure
             (PCWPm) or left ventricular end diastolic pressure (LVEDP) > 15 mmHg or left
             ventricular ejection fraction (LVEF) < 45% (as assessed by either multigated
             acquisition [MUGA] scan, angiography or echocardiography), or symptomatic coronary
             artery disease (i.e., demonstrable ischemia either at rest or during exercise)

          8. Had acute pulmonary embolism (less than 6 months), chronic thromboembolic disease,
             pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis

          9. Had an atrial septostomy

         10. Had a current diagnosis of uncontrolled sleep disordered breathing

         11. Had PH associated with:

               1. chronic obstructive lung disease (COPD), cystic fibrosis, emphysema, alveolar
                  hypoventilation disorders, chronic exposure to high altitude, developmental
                  abnormalities, schistosomiasis, or chronic hemolytic anemia

               2. hematologic disorders (myeloproliferative disorders, splenectomy)

               3. metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders

               4. pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis,
                  neurofibromatosis, vasculitis

               5. tumoral obstruction, fibrosing mediastinitis, or extensive loss of lung tissue
                  from surgery or trauma

         12. Had chronic renal insufficiency as defined by either a Screening creatinine value
             greater than 2.5 mg/dL (221 μmol/L) or the requirement for dialysis.

         13. Had liver function tests (AST or ALT) greater than three times the upper limit of
             normal at Screening.

         14. Had anemia as defined by a Screening hemoglobin value of less than 10 g/dL, active
             infection, or any other condition that would interfere with the interpretation of
             study assessments.

         15. Had uncontrolled systemic hypertension as evidenced by systolic blood pressure greater
             than 160 mmHg or diastolic blood pressure greater than 100 mmHg.

         16. Was pregnant or nursing.

         17. Had an unstable psychiatric condition or was mentally incapable of understanding the
             objectives, nature, or consequences of the trial, or had any condition which in the
             Investigator's opinion would constitute an unacceptable risk to the subject's safety.

         18. Was receiving an investigational drug, had an investigational device in place or had
             participated in an investigational drug or device study within 30 days prior to
             Screening.