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

• ClinicalTrials.gov Identifier: NCT00741819
• Recruitment Status: Completed
• First Posted: August 26, 2008
• Results First Posted: February 20, 2013
• Last Update Posted: February 20, 2013
• Sponsor: United Therapeutics
• Information provided by (Responsible Party): United Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Arterial Hypertension	Drug: Inhaled treprostinil	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 73 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: September 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: December 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Inhaled treprostinil; 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; Other Name: Tyvaso

Outcome Measures

Primary Outcome Measures :

1. Number of Adverse Events [ Time Frame: up to 24 months ]
   Overall safety of transitioning from inhaled iloprost to inhaled treprostinil was assessed by type and frequency of adverse events.

Secondary Outcome Measures :

1. Six-minute Walk Distance (6MWD) [ Time Frame: Baseline and 12 weeks ]
   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.
2. Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) [ Time Frame: Baseline and 12 weeks ]
   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.
3. Treatment Satisfaction Questionnaire of Medication (TSQM) [ Time Frame: Baseline and 12 weeks ]
   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.
4. Patient Impression of Change [ Time Frame: Baseline and 12 weeks ]
   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.
5. N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline and Week 12 ]
   Change in NTpro-BNP from Baseline to Week 12. Blood samples were collected for plasma NTpro-BNP analysis during the study.
6. World Health Organization (WHO) Functional Class [ Time Frame: Baseline and 12 Weeks ]
   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.
7. Drug Administration Activities Questionnaire [ Time Frame: Baseline and 12 weeks ]
   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).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama Birmingham

Birmingham, Alabama, United States, 35294

United States, California

UCSD Medical Center

La Jolla, California, United States, 82037

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States, 90095

United States, Kansas

Kansas University Medical Center

Kansas City, Kansas, United States, 66160

United States, New York

Long Island Jewish Medical Center - North Shore

New Hyde Park, New York, United States, 11040

Beth Israel Medical Center

New York City, New York, United States, 10003-3314

Cornell University Medical Center

New York City, New York, United States, 10021

Columbia Presbyterian Medical Center

New York, New York, United States, 10032

Mary M. Parkes Center for Asthma, Allergy and Pulmonary Care

Rochester, New York, United States, 14623

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Ohio State University Medical Center

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States, 15212

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Sponsors and Collaborators

United Therapeutics

More Information

• Responsible Party: United Therapeutics
• ClinicalTrials.gov Identifier: NCT00741819
• Other Study ID Numbers: RIN-PH-401
• First Posted: August 26, 2008
• Results First Posted: February 20, 2013
• Last Update Posted: February 20, 2013
• Last Verified: January 2013

Keywords provided by United Therapeutics:

pulmonary arterial hypertension; PAH; treprostinil sodium; inhalation; ventavis; iloprost

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Hypertension, Pulmonary; Lung Diseases; Treprostinil; Antihypertensive Agents