Safety Study Extension of Iloprost Power 15 in Pulmonary Arterial Hypertension (PROWESS 15 Ext)

A Multicenter, Double-blind, Randomized Study Comparing the Safety and Tolerability of Iloprost Inhalation Solution Delivered by I-neb Utilizing Power Disc-15 and Power Disc-6 in Patients With Symptomatic Pulmonary Arterial Hypertension

Patients with symptomatic idiopathic (IPAH) or familial (FPAH) pulmonary arterial hypertension in New York Heart Association (NYHA) class II to IV , naive to PAH treatment or currently being treated with a stable dose of either bosentan or sildenafil and who complete PROWESS 15 will be enrolled in the PROWESS 15 Extension study. This is a double-blind (12 week), randomized study to compare the safety and tolerability of inhaled iloprost power disc-15 and power disc-6 in patients with symptomatic pulmonary arterial hypertension (PAH). After completion of the double blind period, patients will be entered in the open label period using iloprost power disc-15.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: iloprost; Drug: iloprost

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LHK Universitatsklinikum Graz
• Germany
  • Dresden, Germany, D-01307
    • Universitätsklinikum Carl-Gustav-Carus
• United States
  • California
    • La Jolla, California, United States, 92037
      • UCSD Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Torrance, California, United States, 90502
      • Liu Center for Pulmonary Hypertension - LA Biomedical Research Institute at Harbor-UCLA
  • Delaware
    • Newark, Delaware, United States, 19713
      • Lung Health & Sleep Enhancement Center, LLC
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Pulmonary & Critical Care of Atlanta
    • Decatur, Georgia, United States, 30033
      • Atlanta Institute for Medical Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • Iowa City, Iowa, United States, 52245
      • Mercy Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Associates
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7020
      • University of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Clinical Trial Center
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Health System
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Lexington, South Carolina, United States, 29072
      • Lexington Pulmonary & Critical Care
  • Texas
    • Dallas, Texas, United States, 75390-8550
      • UT Southwestern Medical Center Heart Lung and Vacular Center
    • Houston, Texas, United States, 77030
      • University of Texas Medical School
  • Utah
    • American Fork, Utah, United States, 84003
      • Central Utah Clinic, P.C.
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Hospitals T/A Sentara Cardiovascular Research Institute
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Respiratory Consultants
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Hospital & Clinics
    • Milwaukee, Wisconsin, United States, 53215
      • Comprehensive Cardiovascular Care LLP

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed informed consent prior to initiation of any study mandated procedure,
2. Patients with symptomatic idiopathic or familial pulmonary arterial hypertension in NYHA functional class II to IV who have completed study AC-063A301,
3. Women of childbearing potential must have a negative urine pregnancy test and must use an adequate method of contraception during the study and for 28 days after discontinuation of the study drug.

Exclusion Criteria:

1. Pulmonary arterial hypertension related to any condition other than those specified in the inclusion criteria,
2. Pulmonary arterial hypertension associated with significant venous or capillary involvement (Pulmonary capillary wedge pressure (PCWP) > 15 mmHg), known pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis,
3. Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 65% of predicted value after bronchodilator administration,
4. Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value,
5. Pregnant or breast-feeding women,
6. Systemic hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg on repeated measurement),
7. Systolic blood pressure < 95 mmHg,
8. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C,
9. Chronic renal insufficiency defined by serum creatinine > 2.5 mg/dL (221 μmol/L) or ongoing dialysis,
10. Clinically relevant bleeding disorder or active bleeding,
11. Known hypersensitivity to iloprost or any of its excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: iloprost power 6; iloprost power 15	Drug: iloprost; Iloprost 5 mcg delivered by I-neb(R) adaptive aerosol delivery (AAD)(R) System power disc-6 administered 6 to 9 times per day for 12 weeks. If patient enters open label follow-up period, iloprost 5 mcg delivered by I-neb(R)AAD(R) System power disc-15 administered 6 to 9 times per day until the end of study.; Other Names: Ventavis; Drug: iloprost; Iloprost 5 mcg delivered by I-neb(R)AAD(R) System power disc-15 administered 6 to 9 times per day for 12 weeks. If patient enters open label follow-up period, iloprost 5 mcg delivered by I-neb(R)AAD(R) System power disc-15 administered 6 to 9 times per day until the end of study.; Other Names: Ventavis
Experimental: iloprost power 15	Drug: iloprost; Iloprost 5 mcg delivered by I-neb(R) adaptive aerosol delivery (AAD)(R) System power disc-6 administered 6 to 9 times per day for 12 weeks. If patient enters open label follow-up period, iloprost 5 mcg delivered by I-neb(R)AAD(R) System power disc-15 administered 6 to 9 times per day until the end of study.; Other Names: Ventavis; Drug: iloprost; Iloprost 5 mcg delivered by I-neb(R)AAD(R) System power disc-15 administered 6 to 9 times per day for 12 weeks. If patient enters open label follow-up period, iloprost 5 mcg delivered by I-neb(R)AAD(R) System power disc-15 administered 6 to 9 times per day until the end of study.; Other Names: Ventavis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent Adverse Events	Number of adverse events	Double-blind period: from first inhalation of study drug to end of 12-week treatment period. Open-label period: from the start to end of open-label medication, mean duration of exposure was 284.5 days.
Treatment-emergent Serious Adverse Events	Number of serious adverse events	Double-blind period: from first inhalation of study drug to end of 12-week treatment period. Open-label period: from the start to end of open-label medication, mean duration of exposure was 284.5 days.
Adverse Events Leading to Premature Discontinuation of Study Drug	Number of adverse events leading to discontinuation of study treatment	Double-blind period: from the first inhalation of study drug to discontinuation. Open-label period: from the start of open-label medication to discontinuation, mean duration of exposure was 284.5 days.
Patients With Adverse Events Leading to Premature Discontinuation of Study Drug	Number of patients with adverse events leading to discontinuation of study treatment	Double-blind period: from the first inhalation of study drug to discontinuation. Open-label period: from the start of open-label medication to discontinuation, mean duration of exposure was 284.5 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Inhalation Time	Average inhalation time of iloprost during the double-blind period (i.e., the sum of the duration of each inhalation divided by the number of inhalations during the double-blind period)	12 weeks

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Laila Rouault, MD, Actelion

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: July 1, 2008
• First Submitted That Met QC Criteria: July 2, 2008
• First Posted (Estimate): July 3, 2008

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: September 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: iloprost; pulmonary arterial hypertension; Ventavis; inhaled treatment; inhalation solution
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: AC-063A302