Clinical trial NCT00723554: Iloprost Power Disc-15 in Pulmonary Arterial Hypertension
Official title: A Phase IIIb, Multicenter, Open-label Study of Patients With Pulmonary Arterial Hypertension Treated With Iloprost(Inhalation)Evaluating Safety and Inhalation Times When Converting From Power Disc-6 (PD-6) to Power Disc-15 (PD-15) With the I-neb® AAD®
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: pulmonary arterial hypertension
inhaled therapy
power disc-15
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2008-07-28
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase IIIb, Multicenter, Open-Label Study of Patients With Pulmonary Arterial Hypertension Treated With Iloprost(Inhalation)Evaluating Safety and Inhalation Times When Converting From Power Disc-6 to Power Disc-15 With the I-neb® Adaptive Aerosol Delivery® System (I-neb® AAD®)


Eligibility criteria: Inclusion Criteria:

* Signed informed consent prior to initiation of any study-mandated procedure.
* Male or female patients aged 18-85 years.
* Patients with symptomatic pulmonary arterial hypertension in New York Heart Association (NYHA) functional class III or IV at the time of initiation of iloprost inhalation (Ventavis®) therapy using the Power Disc-6 (PD-6).
* Patients with the following types of pulmonary arterial hypertension (PAH) belonging to World Health Organization (WHO) Group I:

  * 1.1: Idiopathic (IPAH)
  * 1.2: Familial (FPAH)
  * 1.3: Associated with (APAH)

    * 1.3.1: Collagen vascular disease
    * 1.3.2: Congenital systemic-to-pulmonary shunts at least 2 years post surgical repair
    * 1.3.4: Human immunodeficiency virus (HIV) infection
    * 1.3.5: Drugs and toxins
* PAH confirmed by the most recent right heart catheterization showing:

  * Mean pulmonary arterial pressure (mPAP)≥ 25 mmHg at rest
  * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg. If both PCWP and LVEDP are available then the LVEDP value is retained for inclusion.
  * Pulmonary vascular resistance (PVR) \> 240 dyn-sec/cm\^5
* Compliant with a treatment regimen of commercial iloprost inhalation (Ventavis® 5 μg) using the I-neb® AAD® equipped with the PD-6 for at least 4 weeks prior to screening.
* Pulmonary function tests (PFTs) including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and total lung capacity (TLC), performed within 6 months of screening.
* If taking other medications for PAH, these must have been stable for 60 days prior to baseline.
* If taking corticosteroids, these must have been stable for 60 days prior to baseline.
* Women of childbearing potential with a negative urine pre-treatment pregnancy test at baseline and who:

  * consistently and correctly use (from screening and up to 28 days after discontinuation of study drug) a reliable method of contraception with a Pearl index of \< 1%,
  * are sexually abstinent, or
  * have a vasectomized partner.

A woman is considered to have childbearing potential unless she meets at least one of the following criteria:

* Previous bilateral salpingo-oophorectomy or hysterectomy
* Premature ovarian failure confirmed by a specialist gynecologist
* XY genotype, Turner syndrome, uterine agenesis
* Is aged \> 50 years and not treated with any kind of hormone replacement therapy (HRT) for at least 2 years prior to screening, with amenorrhea for at least 24 consecutive months

Exclusion Criteria:

* PAH belonging to WHO group II-V.
* PAH belonging to WHO group I other than that listed in the inclusion criteria, i.e., PAH associated with:

  * 1.3.3: Portal hypertension
  * 1.3.6: Other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy)
  * 1.4: Associated with significant venous or capillary involvement:

    * 1.4.1: Pulmonary veno-occlusive disease (PVOD)
    * 1.4.2: Pulmonary capillary hemangiomatosis (PCH).
* Receipt of any prostacyclin or prostacyclin analog other than iloprost within 12 weeks before screening.
* Anticipation of the need for intravenous prostacyclin use within 28 days of starting the Power Disc-15 (PD-15).
* HIV-seropositive with any of the following:

  * Concomitant active opportunistic infections within 6 months prior to screening
  * Detectable viral load within 6 months of screening
  * CD4+ T-cell count \< 200 mm\^3 within 3 months of screening
  * Changes in antiretroviral regimen within 3 months of screening
  * Anticipated changes in antiretroviral regimen during study periods 1 or 2
  * Using inhaled pentamidine
* Systemic hypotension with systolic blood pressure \< 95 mmHg.
* Uncontrolled systemic hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg on repeated measurement).
* History of left-sided heart disease, including any of the following:

  * hemodynamically significant aortic or mitral valve disease
  * restrictive or congestive cardiomyopathy
  * left ventricular ejection fraction \< 40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography
  * coronary artery disease with continuing symptoms of angina pectoris
  * life-threatening cardiac arrhythmias
* Atrial septostomy within 1 year.
* History of pulmonary embolism prior to diagnosis of PAH unless it can be documented that chronic thromboembolic pulmonary hypertension (CTEPH) has been specifically excluded (e.g., ventilation/perfusion (VQ) scan, pulmonary angiogram).
* Restrictive lung disease: TLC \< 60% of normal predicted value.
* Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) \< 0.5 or clinically relevant chronic obstructive lung disease or asthma (including any patient requiring concomitant medication to control symptoms of bronchospasm including as needed (p.r.n.) use).
* Clinically relevant bleeding disorder or active bleeding.
* Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C or hepatic cirrhosis.
* Pregnant or breast-feeding.
* Chronic renal insufficiency, as defined by a creatinine of \> 2.5 mg/dL or the requirement for dialysis.
* Hemoglobin \< 75% of the lower limit of normal range.
* Any condition that prevents compliance with the protocol or adherence to therapy or ability to provide informed consent.
* Participation in any other clinical trial, except observational, or receipt of an investigational product within 30 days prior to enrollment.

Primary outcomes:
measure: Number of Patients Reporting Treatment-emergent Adverse Events (AEs)
timeFrame: From the first dose to last dose of investigational product, an average of approximately 268 days, plus 48 hours
measure: Number of Patients Who Discontinued Iloprost PD-15 Treatment Due to an AE
timeFrame: From the first dose of investigational product to study discontinuation, an average of approximately 268 days
measure: Number of Patients Reporting Treatment-emergent Serious AEs
timeFrame: From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours
measure: Systolic Blood Pressure - Iloprost PD-6 (Period 1)
timeFrame: Day 1
measure: Systolic Blood Pressure - Iloprost PD-15 (Period 2)
timeFrame: Day 28
measure: Systolic Blood Pressure - Iloprost PD-15 (Period 3)
timeFrame: an average of approximately 268 days
measure: Change in Systolic Blood Pressure - (Period 1 to Period 2)
timeFrame: Day 1 and Day 28
measure: Change in Systolic Blood Pressure - (Period 1 to Period 3)
timeFrame: Day 1 and End of study visit, an average of approximately 268 days
measure: Diastolic Blood Pressure - Iloprost PD-6 (Period 1)
timeFrame: Day 1
measure: Diastolic Blood Pressure - Iloprost PD-15 (Period 2)
timeFrame: Day 28
measure: Diastolic Blood Pressure - Iloprost PD-15 (Period 3)
timeFrame: an average of approximately 268 days
measure: Change in Diastolic Blood Pressure - (Period 1 to Period 2)
timeFrame: Day 1 and Day 28
measure: Change in Diastolic Blood Pressure - (Period 1 to Period 3)
timeFrame: Day 1 and End of study visit, an average of approximately 268 days
measure: Heart Rate - Iloprost PD-6 (Period 1)
timeFrame: Day 1
measure: Heart Rate - Iloprost PD-15 (Period 2)
timeFrame: Day 28
measure: Heart Rate - Iloprost PD-15 (Period 3)
timeFrame: an average of approximately 268 days
measure: Change in Heart Rate - (Period 1 to Period 2)
timeFrame: Day 1 and Day 28
measure: Change in Heart Rate - (Period 1 to Period 3)
timeFrame: Day 1 and End of study visit, an average of approximately 268 days
Secondary outcomes:
measure: Average Inhalation Time - Iloprost PD-6 (Period 1)
timeFrame: average of approximately 28 days
measure: Average Inhalation Time - Iloprost PD-15 (Period 2)
timeFrame: average of approximately 28 days
measure: Average Inhalation Time - Iloprost PD-15 (Period 3)
timeFrame: average of approximately 240 days
measure: Change in Average Inhalation Time - (Period 1 to Period 2)
timeFrame: average approximately 56 days
measure: Average Number of Days of Dosing - Iloprost PD-6 (Period 1)
timeFrame: average of approximately 28 days
measure: Average Number of Days of Dosing - Iloprost PD-15 (Period 2)
timeFrame: average of approximately 28 days
measure: Average Number of Days of Dosing - Iloprost PD-15 (Period 3)
timeFrame: average of approximately 240 days
measure: Change in Average Number of Days of Dosing - (Period 1 to Period 2)
timeFrame: average approximately 56 days
measure: Average Number of Daily Doses - Iloprost PD-6 (Period 1)
timeFrame: average of approximately 28 days
measure: Average Number of Daily Doses - Iloprost PD-15 (Period 2)
timeFrame: average of approximately 28 days
measure: Average Number of Daily Doses - Iloprost PD-15 (Period 3)
timeFrame: average of approximately 240 days
measure: Change in Average Number of Daily Doses - (Period 1 to Period 2)
timeFrame: average approximately 56 days
measure: Percentage of Complete Doses Delivered - Iloprost PD-6 (Period 1)
timeFrame: average of approximately 28 days
measure: Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 2)
timeFrame: average of approximately 28 days
measure: Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 3)
timeFrame: average of approximately 240 days
measure: Change in Percentage of Complete Doses Delivered - (Period 1 to Period 2)
timeFrame: average approximately 56 days
measure: New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15)
timeFrame: average of approximately 28 days
measure: NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28)
timeFrame: average of approximately 28 days
measure: NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit))
timeFrame: average of approximately 268 days
measure: Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28)
timeFrame: average approximately 28 days
measure: Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit)
timeFrame: average approximately 268 days
measure: Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15)
timeFrame: average of approximately 28 days
measure: Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28)
timeFrame: average of approximately 28 days
measure: Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit))
timeFrame: average of approximately 268 days
measure: Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28
timeFrame: average of approximately 28 days
measure: Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit
timeFrame: average of approximately 268 days
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Medical
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Associates, Ltd.
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Foundation Hospital
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Healthcare Center
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Sarasota
country: United States
facility: Suncoast Lung Research, LLC
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associates
state: Kentucky
city: New Orleans
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: North Shore Long Island Jewish Health System
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Syracus
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University, The Dorothy M. Davis Heart & Lung Research Institute
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center, Inc.
state: Oklahoma
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center-Presbyterian
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Provo
country: United States
facility: Central Utah Clinic, P.C.
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Milwaukee
country: United States
facility: Comprehensive Cardiovascular Care Group LLC
state: Wisconsin
Study officials:
References: