Iloprost Power Disc-15 in Pulmonary Arterial Hypertension

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.