Iloprost Power Disc-15 in Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: Iloprost PD-6; Iloprost PD-15
Intervention description: Period 1 (PD-6): study period defined as the 14 days prior to the first dose of study iloprost inhalation with PD-15. Commercial iloprost inhalation solution delivered using the Power Disc-6 with the I-neb® Adaptive Aerosol Delivery (AAD®) system administered 6 to 9 times per day; Period 2 (PD-15): study period between the administration of the first dose with PD-15 on Day 1 until Day 28 inclusive.
Period 3 (PD-15): study period from Day 29 until discontinuation of the PD-15. Commercial iloprost inhalation solution delivered using the Power Disc-15 with the I-neb® Adaptive Aerosol Delivery (AAD®) system administered 6 to 9 times per day
Intervention MeSH terms: Iloprost
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: pulmonary arterial hypertension; inhaled therapy; power disc-15

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.