Effects of Inhaled Treprostinil Sodium for the Treatment of Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
Condition: Idiopathic Pulmonary Fibrosis; Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Hypertension; Fibrosis
Intervention: Treprostinil sodium for inhalation
Intervention description: Administration of inhaled treprostinil sodium 0.6 mg/ml in 3mL ampoules Duration of Treatment: single dose
Dose:
Cohort 1: dosed at 3 breaths (18 mcg)
Cohort 2: dosed at 6 breaths (36 mcg)
Cohort 3: dosed at 9 breaths (54 mcg)
Cohort 4: dosed at 12 breaths (72 mcg)
The decision to advance to the next cohort will be made after review of all safety information including vital signs, physical examination, clinical laboratory tests, ECGs, and adverse events.
Intervention MeSH terms: Treprostinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 35 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: fibrosis, pulmonary; hypertension, pulmonary; exercise, aerobic

Summary:

      The purpose of this study is to establish single-dose tolerability of inhaled treprostinil
      sodium in idiopathic pulmonary fibrosis (IPF) patients with pulmonary hypertension, and to
      explore the acute hemodynamic effects over a range of tolerable doses. The safety and
      pharmacodynamic information obtained from this study will inform the design and conduct of
      future studies in inhaled treprostinil sodium in this population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  35 to 80 years of age

          -  Male or female

          -  Diagnosis of IPF

               1. Investigator diagnosis based on history, physical examination, HRCT,and pulmonary
                  function testing

               2. Clinical symptoms of IPF for at least three months prior to Visit 1

               3. High Resolution CT scan showing definite or probable IPF (any time in the past).
                  Bibasilar reticular abnormalities with minimal ground glass opacities on HRCT
                  scan must also be present (at any time in the past)

               4. Surgical lung biopsy showing usual interstitial pneumonia, or transbronchial lung
                  biopsy that was not diagnostic of an alternative condition. For patients younger
                  than 50 years, a surgical lung biopsy is required (at any time in the past)

               5. FVC ≥ 30 % and < 70% of predicted value within three months prior to Visit 1

               6. DLCO ≥ 15% and <70% of predicted value within three months prior to Visit 1.

          -  Diagnosis of PH

               1. Previously documented radiographic or echocardiographic findings suggestive of
                  pulmonary hypertension

               2. Prior right heart catheterization diagnostic of pre-capillary pulmonary
                  hypertension. [The presence of pre-capillary pulmonary hypertension will be
                  verified by right heart catheterization during Study Visit 3, before enrollment
                  and administration of study drug].

          -  No changes in concomitant medications prescribed to treat PAH or IPF for 30 days to
             Visit 1

          -  Females of childbearing potential may participate only if they are not currently
             pregnant or lactating and are either one of the following:

               1. Surgically sterile

               2. At least 1 year post-menopausal

               3. Practicing an acceptable method of birth control for at least 30 prior to the
                  Visit 1 with plans to continue this method for the duration of their
                  participation in the study.

          -  An echocardiogram will be performed at Visit 2. Only those subjects with Visit 2
             echocardiographic findings that strongly suggest the presence of pulmonary
             hypertension, will proceed to Visit 3. Acceptable findings include any of the
             following:

               1. TR velocity greater than 3.5 m/sec

               2. TR velocity greater than 3.0 m/sec with right ventricular enlargement or
                  dysfunction

          -  A right heart catheterization will be performed at Visit 3. Only those subjects with
             Visit 3 right heart catheterization findings that establish the presence of pulmonary
             hypertension will proceed to enrollment and study drug administration. Acceptable
             findings must include all of the followings:

               1. mean PA pressure equal or greater than 25 mm HG

               2. pulmonary capillary wedge pressure equal or less than 15 mm Hg

               3. pulmonary vascular resistance greater than 3 mmHg/min

        Exclusion Criteria:

        A subject will not be eligible for inclusion in this study if ANY of the following criteria
        apply:

          -  History of known or suspected pulmonary embolism or deep venous thrombosis

          -  Clinical evidence of left-sided heart disease

          -  Presence of atrial fibrillation (determined from 12 lead ECG at Visit 1 or 2)

          -  Other medical condition or drug exposure known to be associated with pulmonary
             fibrosis (e.g., rheumatoid arthritis, lupus, scleroderma, etc.) or pulmonary arterial
             hypertension (e.g., connective tissue disease, congenital heart disease, portal
             hypertension, HIV infection, drug and toxins, etc.)

          -  Upper or lower respiratory infection within 30 days prior to Visit 1

          -  Hospitalization for respiratory illness within 30 days prior to Visit 1

          -  Diagnosis of any other clinically significant illness that, in the opinion of the
             investigator, might put the subject at risk of harm from participation in the study or
             might adversely effect the interpretation of the study data. (e.g., significant liver
             or kidney disease, etc.)

          -  History of recurrent symptoms that might, in the opinion of the investigator,
             adversely effect the interpretation of the study data (e.g., severe headaches,
             diarrhea, jaw pain, syncope, nausea,vomiting, etc.)

          -  Current treatment with any medication that is approved by the US FDA to treat
             pulmonary hypertension (e.g., epoprostenol(Flolan), treprostinil (Remodulin), iloprost
             (Ventavis), bosentan(Tracleer), ambrisentan (Letairis), sildenafil (Revatio), etc.,),
             or tadalafil (Cialis)

          -  Current treatment with an anticoagulant

          -  A reactive screen for hepatitis B surface antigen, or the hepatitis C antibody, or HIV
             antibody as tested at Visit 1.

          -  Use of any inhaled tobacco products or significant history of drug abuse within 90
             days prior to Visit 1

          -  The subject has an echocardiogram performed at Visit 2 that demonstrate findings that
             are indicative of left ventricular or valvular disease. Findings that will be
             considered evidence of left ventricular or valvular disease, and therefore exclude the
             subject from proceeding to Visit 3 are any of the following:

               1. LVEF < 55%

               2. Moderate to Severe mitral regurgitation or aortic regurgitation

               3. Any mitral stenosis or aortic stenosis

               4. Grade 2 or 3 diastolic dysfunction by Doppler

          -  Use of any investigational drug, or participation in any investigational study within
             the 30 days prior to Visit 1.