Dose Determination Safety and Activity Study of Inhaled NX1011 to Treat Pulmonary Arterial Hypertension

An Open-Label, Dose-Determination Safety, Tolerability, and Activity Study of Inhaled NX1011 in Patients With Pulmonary Arterial Hypertension

The purpose of this study is to determine the safety and maximum tolerated dose of inhaled NX1011 for the treatment of pulmonary arterial hypertension (PAH).

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: NX1011

• Study Type: Interventional
• Enrollment: 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Arizona Pulmonary Specialists, Ltd.
  • California
    • La Jolla, California, United States, 92037
      • University of California, San Diego Medical Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health Services
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must either:

  • meet the PAH diagnostic criteria at Screening (based on a documented history of diagnosis as outlined in the American College of Chest Physicians [ACCP] 2004 Evidence-Based Clinical Practices Guidelines)15; or
  • have elevated pulmonary pressure with a suspected PAH diagnosis based on a clinical referral at Screening for a RHC.
• Patient must have PAH as defined by a mean pulmonary artery pressure (PAP) > 25 mmHg.
• Patient must have symptoms of pulmonary hypertension (PH) according to the World Health Organization (WHO) Functional Classification of Pulmonary Hypertension Class II through IV.
• Patient must consent to, be able to tolerate, and have adequate venous and arterial access for Swan-Ganz catheterization (SGC) and an arterial line.

Exclusion Criteria:

• Clinically significant right-to-left intracardiac shunts based on Doppler echocardiography with bubble study.
• History of pulmonary veno-occlusive disease or clinically significant aortic or mitral stenosis.
• History of sustained ventricular tachycardia (VT-S) or ventricular fibrillation (VF) and cardiac arrest, or presence of atrial fibrillation.

• Active cardiac disease meeting the following criteria:

  • Patient with elevated pulmonary capillary wedge pressures (PCWPs) > 25 mmHg.
  • Patient with a history of myocardial infarction or coronary intervention within the last 60 days.
  • Patient with a history of pacemaker, cardiac defibrillator, or biventricular pacemaker insertion within 4 weeks of Baseline.
  • Patient who cannot be withdrawn from nitrate therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To evaluate the safety, tolerability, and activity of inhalation therapy with NX1011 based on right heart catheterization (RHC) measures, pulse oximetry, and hemodynamic response
To establish maximum tolerated dose (MTD) levels of NX1011 based on predefined criteria for dose-limiting toxicity (DLT)
To qualify the delivery apparatus
To generate descriptive data on the concentration-response relationship in order to choose a range of concentrations (e.g., low, medium, high) for the follow-up, fixed-dose, placebo-controlled study
To summarize correlation data between echocardiography and RHC measures with respect to activity and methemoglobin levels documented via the visible light spectroscopy

Secondary Outcome Measures

Outcome Measure
To summarize correlation data between echocardiography and RHC measures with respect to activity and methemoglobin levels documented via the visible light spectroscopy

Collaborators and Investigators

• Sponsor: NITROX, LLC
• Investigators: Study Director: Victoria A Christian, NITROX, LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Study Completion: May 1, 2007

Study Registration Dates

• First Submitted: May 5, 2006
• First Submitted That Met QC Criteria: May 5, 2006
• First Posted (Estimate): May 9, 2006

Study Record Updates

• Last Update Posted (Estimate): August 30, 2007
• Last Update Submitted That Met QC Criteria: August 29, 2007
• Last Verified: July 1, 2006

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Pulmonary Arterial Hypertension; Idiopathic PAH; PH associated with connective tissue disease (CTD); PH associated with interstitial lung disease (ILD); PH associated with congestive heart failure (CHF); PH associated with chronic obstructive pulmonary disease (COPD)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: NX1011:201