Two-Part Dose-Confirming Study of Pulsed Inhaled Nitric Oxide in Subjects With WHO Group 3 Pulmonary Hypertension Associated With COPD
Condition: Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary; Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a placebo-controlled, double-blind, parallel, randomized, two-part, dose-confirming
      clinical study characterizing the pharmacodynamic effects of pulsed iNO using the combination
      product, inhaled nitric oxide/INOpulse DS-C vs. placebo in subjects with World Health
      Organization (WHO) Group 3 pulmonary hypertension (PH) associated with Chronic Obstructive
      Pulmonary Disease (COPD) on Long Term Oxygen Therapy (LTOT).
    

Detailed description: 
      This two-part study is designed to confirm the dose of inhaled nitric oxide (NO),
      administered through an investigational pulsed delivery device (INOpulse® DS-C) that results
      in decreased pulmonary arterial systolic pressure (PASP) without significantly affecting
      systemic oxygenation.

      In Part A, 80 subjects will be randomized to 1of 4 treatment groups in a 1:1:1:1 ratio (with
      20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed
      iNO at a dose of 0.003 mg/kg IBW/hr, 0.010 mg/kg IBW/hr, or 0.015 mg/kg IBW/hr, with a set
      pulse width (PW) of 260 milliseconds (ms). Part A subjects assigned to the placebo group will
      receive nitrogen (N2) at a randomly assigned device setting of 0.003, 0.010 or 0.015 mg/kg
      IBW/hr with a set PW of 260 ms.

      Subjects who were randomized in Part A are permitted to participate in Part B of the study.
      Subjects will need to be re-screened and re-randomized for Part B participation.

      In Part B, 60 subjects will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (with
      20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed
      iNO at either 0.030 mg/kg IBW/hr or 0.075 mg/kg IBW/hr, with a set PW of 260 ms. Part B
      subjects assigned to placebo will receive N2 at a randomly assigned device setting of 0.030
      mg/kg IBW/hr or 0.075 mg/kg IBW/hr with a set PW of 260 ms.

      Part B will use a skewed block randomization scheme with 10 blocks of 6 subjects as follows:

        -  Blocks 1-3: 3 subjects at 0.030 mg/kg IBW/hr, 1 subject at 0.075 mg/kg IBW/hr, and 2
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr

        -  Blocks 4-7: 2 subjects at 0.030 mg/kg IBW/hr, 2 subjects at 0.075 mg/kg IBW/hr, and 2
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr

        -  Blocks 8-10: 1 subject at 0.030 mg/kg IBW/hr, 3 subjects at 0.075 mg/kg IBW/hr, and 2
           subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr
    

Intervention name(s): Inhaled NO delivered via INOpulse DS-C Device; Placebo delivered via INOpulse DS-C Device
Intervention type(s): Combination Product; Combination Product
Intervention description(s): Subjects will be treated with nitric oxide by means of an INOpulse DS-C device using an INOpulse nasal cannula.; Subjects will be treated with nitrogen gas by means of an INOpulse DS-C device using an INOpulse nasal cannula.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Inhaled nitric oxide (iNO); Pulmonary hypertension (PH); Chronic obstructive pulmonary disease (COPD); Long term oxygen therapy (LTOT)