Part 1: Pulmonary Hypertension (PH) Associated with Chronic Obstructive Pulmonary Disease (COPD) Part 2: Pulmonary Hypertension (PH) Associated with Idiopathic pulmonary fibrosis (IPF) MedDRA version: 18.1 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 18.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and medias
Conditions
Interventions
Trade Name: INOmax 400ppm mol/mol inhalation gas
Product Name: INO
Pharmaceutical Form: Pressurised inhalation
INN or Proposed INN: NITRIC OXIDE
CAS Number: 10102-43-9
Current Sponsor code: IK-7002
Co
Sponsors
Bellerophon Pulse Technologies LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1 1. A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive Lung Disease (GOLD) criteria 2. Pulmonary hypertension determined by 1 of the following within the past 12 months a. A right heart catherization (not obtained within ± 7 days of an exacerbation) with an mPAP = 25 mmHg, or b. An echocardiogram (not obtained within ± 7 days of an exacerbation) with a TRV = 2.9 meters per second (m/s), or a systolic PAP = 38 mmHg by 2-D echocardiogram. (Note: a subject with a TRV =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Part 1: 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: a) start of or increase in systemic oral corticosteroid therapy, and/or b) hospitalization 4. Left ventricular dysfunction as measured by: Screening echocardiographic evidence of left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] Grade 2), or Any history of pulmonary capillary wedge pressure (PCWP), left atrial pressure (LAP) or left ventricular end diastolic pressure (LVEDP) > 18 mm Hg 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 moderate (i.e., > Grade 3), or c) 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 4. Renal impairment (i.e., an estimated GFRMDRD < 30 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 Subjects with possible compromised kidney function (eGFRMD
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this exploratory study is to examine the utility of high resolution computed tomography (HRCT) to measure changes in functional pulmonary imaging parameters as a function of short term iNO administration using the medical device INOpulse® in subjects with WHO Group 3 PH associated with COPD (Part 1) and in subjects with WHO Group 3 PH associated with IPF (Part 2) on LTOT. In Part 1 iNO was administered by the investigational INOpulse® DS-C device. In Part 2 the INOpulse® device will be used. ;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint in this exploratory study is the change from baseline in lobar blood volume at total lung capacity (TLC) after dosing with pulsed iNO (Part 1) and iNO or Placebo (Part 2a) as measured by HRCT.;Timepoint(s) of evaluation of this end point: Part 1: Treatment Visit: at Baseline and after administration of iNO Part 2a: Treatment Visit A: at Baseline and after administration of iNO/Placebo and Treatment Visit B (at least 5 Days after Treatment Visit A): at Baseline and after administration of iNO/Placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints in this exploratory study are the changes from baseline measured by HRCT after dosing with pulsed iNO (Part 1) and iNO or Placebo (Part 2a) in: • Blood vessel % and density on lobar level • Total lung volume at TLC • Lobar volumes at TLC • Internal airflow distribution based on lobar expansion • Airway volume down to generation 8-10 at TLC • Computational Fluid Dynamics (CFD)-based resistance on lobar level • Ventilation/perfusion (V/Q) matching Part 2a only (Acute; Placebo vs. iNO 75 mcg/kg IBW/hr) • Change in Borg Dyspnea Score (LTOT, iNO/Placebo + LTOT, LTOT post iNO/Placebo exposure, and 24 hrs post iNO/Placebo exposure) • Changes in breathing questionnaire (LTOT, LTOT post iNO/Placebo exposure, and 24 hrs post iNO/Placebo exposure) • Changes in RV and LV function (LTOT, iNO/Placebo + LTOT, post iNO/Placebo LTOT alone) by echocardiogram Part 2b Only (Chronic dosing) • Change in 6MWT with Borg Dyspnea Score and SpO2, at the beginning and end of the 6MWT and symptoms evaluated using a questionnaire after 4 weeks use of iNO 75 mcg/kg IBW/hr and 2 weeks post discontinuation of iNO ;Timepoint(s) of evaluation of this end point: Part 1: Treatment Visit: at Baseline and after administration of iNO Part 2a only: - HRCT: Treatment Visit A and B: at Baseline and after administration of iNO/Placebo - Borg Dyspnea Score: at Treatment Visit A, B and follow-up: LTOT, iNO/Placebo + LTOT, LTOT post iNO/Placebo exposure, and 24 hrs post iNO/Placebo exposure - breathing questionnaire: at Treatment Visit A, B and follow-up: LTOT, LTOT post iNO/Placebo exposure, and 24 hrs post iNO/Placebo exposure - echocardiogram: at screening, Treatment Visit A and B Part 2b only: - Change in 6MWT with Borg Dyspnea Score and SpO2, at the beginning and end of 6MWT: Visit 1, 2, 3, and 4 - Borg Dyspnea Score: Visit 1, 2, 3, and 4 - breathing questionnaire: Visit 1, 2, 3, and 4 | — |
Countries
Belgium
Contacts
Public ContactJan De Backer
Fluidda nv
Outcome results
None listed