Clinical trial NCT02267655 (phase 1, status: completed)
Conditions: pulmonary hypertension, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis
ICD codes: I27.0, I27.20, I27.21, I27.24, I27.29, P29.30, I27.22, J44.9, J44.1, J44.0, J84.112
Drugs: inhaled nitric oxide - 30 mcg/kg ibw/hr, inhaled nitric oxide 5,10,15 mcg/kg ibw/hr, inhaled nitric oxide 75 mcg/kg ibw/hr
SMILES: OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1NC=NC2=O, OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1NC=NC2=O, OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1NC=NC2=O
Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must meet all of the following inclusion criteria to be enrolled and eligible
             to participate in the study:

               1. A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive
                  Lung Disease (GOLD) criteria

               2. Pulmonary hypertension determined by one of the following within the past 12
                  months:

                    1. A right heart catheterization (not obtained within ± 7 days of an
                       exacerbation) with an mPAP ≥ 25 mmHg, or

                    2. An echocardiogram (not obtained within ± 7 days of an exacerbation) with a
                       TRV ≥ 2.9 m/s or sPAP ≥ 38 mmHg (Note: a subject with an acceptable mPAP ≥
                       25 mmHg determined by right heart catheterization will meet this inclusion
                       criteria even with a TRV < 2.9 m/s)

               3. Current or former smokers with at least 10 pack-years of tobacco cigarette
                  smoking before study entry

               4. Age ≥ 40 years, ≤ 80 years

               5. A post-bronchodilatory FEV1/FVC < 0.7 and a FEV1 < 60% predicted (values obtained
                  within 6 months prior to screening can be used unless obtained within ± 7 days of
                  an exacerbation; otherwise, the test must be performed during screening)

               6. Receiving LTOT for ≥ 3 months and ≥ 10 hours per day as determined by history

               7. Females of childbearing potential must have a negative pre-treatment urine
                  pregnancy test

               8. Signed informed consent prior to the initiation of any study mandated procedures
                  or assessments

        Exclusion Criteria:

          -  Subjects who meet any of the following criteria are not eligible for enrollment:

               1. A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of
                  the Investigator

               2. Lack of patency of nares upon physical examination

               3. Experienced during the last month an exacerbation requiring:

                    1. start of or increase in systemic oral corticosteroid therapy and/or

                    2. hospitalization

               4. Left ventricular dysfunction as measured by:

                    1. Screening echocardiographic evidence of left ventricular systolic
                       dysfunction (left ventricular ejection fraction [LVEF] < 40%), or

                    2. Screening echocardiographic evidence of left ventricular diastolic
                       dysfunction

                       > moderate (i.e., > Grade 2), or

                    3. Any history of pulmonary capillary wedge pressure (PCWP), left atrial
                       pressure (LAP) or left ventricular end diastolic pressure (LVEDP) > 18 mmHg
                       as measured during cardiac catheterization within the past 6 months unless
                       documented to have resolved by a subsequent cardiac catheterization

               5. Renal impairment (i.e., an estimated GFRMDRD < 60 ml/min/1.73 m2) or history of
                  renal failure using the equation (Levey et al., 2007):

                  estimated GFRMDRD = 175×Scr -1.154×Age-0.203 ×1.212 (if black) ×0.742 (if female)

                  where Scr = Standardized serum creatinine

               6. Known allergy to contrast media.

               7. Clinically significant valvular heart disease that may contribute to PH,
                  including mild or greater aortic valvular disease (aortic stenosis or
                  regurgitation) and/or moderate or greater mitral valve disease (mitral stenosis
                  or regurgitation), or status post mitral valve replacement

               8. Use within 30 days of screening or current use of approved PH medications such as
                  sildenafil or bosentan (use of Cialis® or Viagra® for erectile dysfunction is
                  permitted)

               9. Use of investigational drugs or devices within 30 days prior to enrollment into
                  the study

              10. Any underlying medical or psychiatric condition that, in the opinion of the
                  Investigator, makes the subject an unsuitable candidate for the study