Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects

Study Overview
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Brief Summary
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This is a 24-month, multi-center, prospective, open-label, safety evaluation in PAH subjects following transition from a stable dose of inhaled iloprost (Ventavis). Subjects are to be evaluated for safety throughout the course of the study while secondary assessments will be conducted at Baseline, Week 6, Week 12, and Months 6, 12, 18 and 24 following initiation of treprostinil sodium.

Official Title
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An Open Label, Multi-center Study Evaluating the Safety of Long-term Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis® (Iloprost) in Subjects With Pulmonary Arterial Hypertension.

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Inhaled treprostinil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18 and 75 years of age PAH diagnosis defined by following WHO Group I categories: idiopathic/familial, associated with unrepaired or repaired congenital systemic-to-pulmonary shunts (repaired >/= 5 years), associated with collagen vascular disease, associated with HIV, associated with appetite suppressant/toxin use Baseline six-minute walk distance (6MWD) >/= 250 meters Currently receiving Ventavis and be stable at current dose for 30 days prior to Baseline If currently receiving other approved background therapy (i.e. endothelin receptor antagonist or phosphodiesterase-5-inhibitor or both) must be on stable dose for 30 days prior to Baseline Previous testing (e.g. right heart catheterization, echocardiography) consistent with diagnosis of PAH Exclusion Criteria: Nursing or pregnant Has acute concomitant disease (e.g. portal hypertension, chronic thromboembolic disease, pulmonary veno-occlusive disease, etc) other than those accepted as part of the inclusion criteria or has had atrial septostomy History of uncontrolled sleep apnea, left-sided heart disease, or parenchymal lung disease Use of investigational drug within 30 days of Baseline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled treprostinil<br>Solution for oral inhalation treprostinil (0.6 mg/mL). Inhaled via an ultrasonic nebulizer which provides a dose of 6mcg of treprostinil per breath. Doses are titrated up to 12 breaths four times daily. | Drug: Inhaled treprostinil<br> <br> * Other names: Tyvaso;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Overall safety of transitioning from inhaled iloprost to inhaled treprostinil was assessed by type and frequency of adverse events. | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-minute Walk Distance (6MWD) | Change in 6MWD from Baseline to Week 12. The 6-minute walk test (6MWT) was conducted at Baseline (10-30 minutes following the last dose of inhaled iloprost) and at Week 12 (10-60 minutes following the dose of inhaled treprostinil). The change in distance (meters) between Baseline and Week 12 is reported below. | Baseline and 12 weeks | 
| Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | Change in CAMPHOR Scores from Baseline to Week 12. The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning)and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements. | Baseline and 12 weeks | 
| Treatment Satisfaction Questionnaire of Medication (TSQM) | Change in TSQM score from Baseline to Week 12. The TSQM is a validated instrument (Health and Quality of Life Outcomes 2004, 2:12) that measures major dimensions of patient satisfaction with medications. The questionnaire is comprised of 15 questions which fall into one of four categories; Effectiveness, Side-Effects, Convenience, and Global Satisfaction. Responses are scaled on a seven point bipolar scale from 'Extremely Satisfied' to 'Extremely Dissatisfied' where higher scores indicate improvements (total scores from 0-100). The questionnaire was completed at Baseline and Week 12. The Baseline questionnaire focused on the subject's satisfaction with inhaled iloprost treatment, while the questionnaire completed at Week 12 focused on the subject's satisfaction with inhaled treprostinil. | Baseline and 12 weeks | 
| Patient Impression of Change | The patient impression of change (PIC) was three single therapy-related questions related to the subjects overall impression of the transition from inhaled iloprost to inhaled treprostinil. Subjects were surveyed related to their overall impression of the transition from inhaled iloprost to inhaled treprostinil at Week 12. | Baseline and 12 weeks | 
| N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) | Change in NTpro-BNP from Baseline to Week 12. Blood samples were collected for plasma NTpro-BNP analysis during the study. | Baseline and Week 12 | 
| World Health Organization (WHO) Functional Class | Change in WHO Functional Class (FC) from Baseline to Week 12. Data presented as percent of subjects who either improved FC, worsened FC, or had no change in FC from Baseline to Week 12. | Baseline and 12 Weeks | 
| Drug Administration Activities Questionnaire | Change in tasks from Baseline to Week 12. At Baseline and Week 12, subjects provided information related to the daily administration and time requirements of inhaled iloprost (Baseline) and inhaled treprostinil (Week 12). | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAH, pulmonary arterial hypertension, treprostinil sodium, inhalation, ventavis, iloprost