Study in Subjects With PAH and PH Secondary to IPF Using Inhaled NITROsyl (PHiano)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Geno LLC
Sponsor:
Information provided by (Responsible Party):
Geno LLC
ClinicalTrials.gov Identifier:
NCT01265888
First received: December 20, 2010
Last updated: April 4, 2013
Last verified: April 2013
  Purpose

A Phase 2 open label, dose escalation study to find the minimally and maximum effective dose (dose beyond which no further effect on PVR is seen) of inhaled nitric oxide generated by the GeNO NITROsyl System compared to placebo.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Idiopathic Pulmonary Fibrosis
Drug: Inhaled Nitric Oxide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Dose-Escalation Study in Subjects With Pulmonary Arterial Hypertension, (PAH, WHO Group 1) and Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis, (PH-IPF WHO Group 3) Using Inhaled NITROsyl.

Resource links provided by NLM:


Further study details as provided by Geno LLC:

Primary Outcome Measures:
  • Identify the minimally and maximum effective doses of inhaled nitric oxide generated by the GeNO NITROsyl System compared to placebo. [ Time Frame: through end of Right Heart Catheterization procedure (Treatment Phase approximately 3 hours) ] [ Designated as safety issue: Yes ]

    Assess mean change in pulmonary vascular resistance (PVR) for study drug dose 2 compared to placebo.

    Assess change from pre-dose to end-of-hemodynamic assessment for study drug dose 1.

    Assess change from placebo to end-of-hemodynamic assessment for study drug dose 2.



Secondary Outcome Measures:
  • Assess the safety and tolerability of nitric oxide generated by the GeNO NITROsyl System in subjects with WHO Group 1 PAH and WHO Group 3 PH-IPF. [ Time Frame: through end of study (approximately 30 days after treatment visit) ] [ Designated as safety issue: Yes ]
  • Evaluate the pharmacokinetics of total nitrates/nitrites and methemoglobin produced following inhalation of nitric oxide via the GeNO NITROsyl System. [ Time Frame: up through 24 hrs after treatment period for subjects participating in PK sub-study ] [ Designated as safety issue: Yes ]
    Individual pharmacokinetic parameters for total nitrates/nitrites and methemoglobin will be summarized with descriptive characteristics.


Estimated Enrollment: 75
Study Start Date: March 2011
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dosing Group 1
1 Liter per Minute (LPM)of inhaled nitric oxide via nasal cannula: approximately 5 parts per million (ppm)
Drug: Inhaled Nitric Oxide
Inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM for 15 minutes followed by placebo washout of 15 minutes inhalation of medical grade air (or prescribed supplemental oxygen), and then inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM
Other Name: NITROsyl
Experimental: Dosing Group 2
2 LPM of inhaled nitric oxide via nasal cannula: approximately 15 ppm
Drug: Inhaled Nitric Oxide
Inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM for 15 minutes followed by placebo washout of 15 minutes inhalation of medical grade air (or prescribed supplemental oxygen), and then inhaled nitric oxide 80 ppm via nasal cannula at 2 LPM
Other Name: NITROsyl
Experimental: Dosing Group 3
4 LPM of inhaled nitric oxide via nasal cannula: approximately 20 ppm
Drug: Inhaled Nitric Oxide
Inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM for 15 minutes followed by placebo washout of 15 minutes inhalation of medical grade air (or prescribed supplemental oxygen), and then inhaled nitric oxide 80 ppm via nasal cannula at 4 LPM
Other Name: NITROsyl
Experimental: Dosing Group 4
6 LPM of inhaled nitric oxide via ventimask: approximately 30 ppm
Drug: Inhaled Nitric Oxide
Inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM for 15 minutes followed by placebo washout of 15 minutes inhalation of medical grade air (or prescribed supplemental oxygen), and then inhaled nitric oxide 80 ppm via ventimask at 6 LPM.
Other Name: NITROsyl
Experimental: Dosing Group 5
12-15 LPM of inhaled nitric oxide via non-rebreather: approximately 80 ppm
Drug: Inhaled Nitric Oxide
Inhaled nitric oxide 80 ppm via nasal cannula at 1 LPM for 15 minutes followed by placebo washout of 15 minutes inhalation of medical grade air (or prescribed supplemental oxygen), and then inhaled nitric oxide 80 ppm via non-rebreather at 12-15 LPM.
Other Name: NITROsyl

Detailed Description:

Up to 75 subjects undergoing RHC are planned in this study, and shall include subjects meeting eligibility criteria classified as WHO Group 1 PAH or WHO Group 3 IPF-PH. Subjects will receive inhaled nitric oxide from the GeNO NITROSYL™ System to characterize the hemodynamic response and evaluate safety and tolerability.

Dose cohorts of approximately 5, 15, 20, 30, and 80 ppm nitric oxide in air will be studied. Different dose levels will be achieved by varying the flow rate of the drug substance (80 ppm NO2 in balance air) and changing the delivery device, (cannula or mask). Each subject will receive two different doses of inhaled nitric oxide separated by a placebo (medical grade air or supplemental oxygen) washout. Eligible subjects will be assigned to a dosing cohort in an escalating manner to receive study drug (80 ppm nitric oxide in air.)

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

PAH and PH-IPF

  • WHO Functional Class (or equivalent classification) II - IV.
  • Subjects using supplemental oxygen must be receiving a stable course of therapy for a minimum of 14 days prior to study drug administration.
  • All subjects' oxygen saturation must be > or = to 88% at time of treatment
  • Echocardiogram within 6 months of baseline showing no signs of clinically significant left sided heart disease
  • Females of child-bearing potential with a negative urine pregnancy test, or a documented surgical sterilization, or is post-menopausal prior to administration of investigational product. Females of childbearing potential must be practicing adequate birth control.

PAH (WHO Group 1) ONLY-Inclusion

  • Documented diagnosis of WHO Group 1 PAH, (limited to, idiopathic, heritable, drug and toxin induced, associated with connective tissue disease, portal hypertension, repaired congenital heart disease, HIV); documented by a previous RHC and hemodynamics consistent with PAH, WHO Group 1
  • Pulmonary Function Testing within 6 months prior to screening/enrollment shows no evidence of interstitial lung disease (TLC<70%) or obstructive lung disease (FEV1/FVC ratio <50%)
  • Receiving a stable course of approved PAH oral mono therapies for a minimum of 14 days prior to treatment period
  • Must be 18-80 year of age

PH-IPF (WHO Group 3) ONLY-Inclusion

  • Documented diagnosis of probable or definite IPF using ATS/ERS criteria
  • Previous transbronchial biopsy, if performed, shows no features to support a definitive alternative diagnosis
  • Previous bronchoalveolar lavage, if performed, shows no features that provides an alternative diagnosis
  • FVC > or = 40% within 6 months of baseline visit
  • Diagnosis of PH based on hemodynamic requirements
  • Age 40-85.
  • Diagnosis of IPF > or = 3 months prior to study drug administration
  • Diagnosis of PH based on the following hemodynamic criteria (PAPm > or = 25 mmHg (at rest) / PCWP or LVED < or =15 mmHg and / PVR >3 Wood Units)

EXCLUSION CRITERIA:

PAH and PH-IPF

  • Have any other disease associated with pulmonary hypertension (i.e. Group II, IV or V).
  • Documented uncontrolled systemic hypertension.
  • Left ventricular ejection fraction (LVEF) < 40%.
  • Have chronic kidney disease stage IV or worse, or requires dialysis.
  • Be receiving an investigational drug, have in place an investigational device, or have participated in an investigational drug study within past 30 days.
  • Have had an atrial septostomy.
  • Have anemia or any other ongoing condition that would interfere with the interpretation of study assessments.
  • Have any serious or life-threatening disease other than conditions associated with PAH or PH-IPF (e.g. malignancy requiring aggressive chemotherapy, renal dialysis, etc.)
  • Significant, ongoing alcohol or drug abuse, or unstable psychiatric status.
  • Receiving inhaled or parenteral prostacyclins or a non-approved combination of approved oral PAH therapy.
  • Pregnant or lactating subjects

PAH (WHO Group 1) ONLY-Exclusion

  • Have had any changes to chronic therapy (including but not limited to oxygen, a different category of vasodilator, a diuretic, digoxin) for PAH added within 14 days of study drug administration. Anticoagulants are allowed to be discontinued per institutional standard of care.
  • History of untreated sleep apnea within three months of study drug administration.
  • History of hemodynamically significant left-sided heart disease or evidence of left-sided heart disease.

PH-IPF (WHO Group 3) ONLY-Exclusion

  • Diagnosis of PH primarily due to etiology other than IPF.
  • FEV/FVC ratio < 60% documented within 6 months of baseline visit.
  • Hospitalization for acute exacerbation of IPF within 30 days of baseline visit.
  • Recent active pulmonary or upper respiratory tract infection.
  • Receiving any approved PAH therapy within 30 days of study drug administration.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01265888

Contacts
Contact: GeNO, LLC 321-785-2613 contactus@genollc.com

Locations
United States, Arizona
Arizona Pulmonary Specialists Recruiting
Phoenix, Arizona, United States, 85012
Principal Investigator: Jeremy Feldman, MD         
University of Arizona Recruiting
Tucson, Arizona, United States, 85704
Principal Investigator: Franz Rischard, MD         
United States, California
VA Greater LA Health Care System-UCLA Recruiting
Los Angeles, California, United States, 90073
Principal Investigator: Shelley Shapiro, MD         
UCLA Medical Center Not yet recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Rajan Saggar, M.D.         
University of California- Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Principal Investigator: Roblee Allen, MD         
United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Principal Investigator: Brett E Fenster, MD         
United States, Kentucky
Kentuckiana Pulmonary Associates Recruiting
Louisville, Kentucky, United States, 40204
Principal Investigator: John W McConnell, MD         
United States, Massachusetts
Brigham & Women's Hospital -Pulmonary and Critical Care Medicine Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Aaron Waxman, MD, PhD         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: Murali Chakinala, MD         
United States, Nebraska
Creighton University Medical Center Completed
Omaha, Nebraska, United States, 68178
United States, New Jersey
University of Medicine and Dentistry of New Jersey Recruiting
Newark, New Jersey, United States, 07103
Principal Investigator: Marc Klapholz, MD         
United States, Ohio
The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Principal Investigator: Peter Engel, MD         
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Principal Investigator: Adriano Tonelli, MD         
Ohio State University, Martha Morehouse Medical Plaza Recruiting
Columbus, Ohio, United States, 43221
Principal Investigator: Namita Sood, MD         
United States, Pennsylvania
Allegheny General Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15212
Principal Investigator: Raymond Benza, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Ivan Robbins, MD         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75239
Principal Investigator: Kelly Chin, M.D.         
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Zeenat Safdar, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Principal Investigator: Nathan Hatton, MD         
United States, Wisconsin
Aurora St. Luke's Medical Center Recruiting
Milwaukee, Wisconsin, United States, 53215
Principal Investigator: Dianne Zwicke, MD         
Sponsors and Collaborators
Geno LLC
Investigators
Study Director: Robert Roscigno, PhD Geno LLC
  More Information

No publications provided

Responsible Party: Geno LLC
ClinicalTrials.gov Identifier: NCT01265888     History of Changes
Other Study ID Numbers: Protocol # GeNO-P-2010-002, PHiano
Study First Received: December 20, 2010
Last Updated: April 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Geno LLC:
PAH
PH IPF

Additional relevant MeSH terms:
Fibrosis
Hypertension
Hypertension, Pulmonary
Idiopathic Pulmonary Fibrosis
Pulmonary Fibrosis
Cardiovascular Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases
Lung Diseases, Interstitial
Pathologic Processes
Respiratory Tract Diseases
Vascular Diseases
Nitric Oxide
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 22, 2014