Inhaled Iloprost (Ventavis): Efficacy, Safety, and Pharmacokinetics (PK) Confirmation Study

Study Overview
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Brief Summary
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This study is to investigate the efficacy, safety, and Pharmacokinetics (PK) of Inhaled Iloprost (Ventavis) therapy in Japanese pulmonary arterial hypertension (PAH) patients in Main Treatment Phase (12 weeks) and to investigate the safety, tolerability, and efficacy of longterm Inhaled Iloprost (Ventavis) therapy in Japanese PAH patients in Extension Phase.

Official Title
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A Multi-center, Non-randomized, Open Label, Single-arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of BAY q 6256 (Iloprost) Inhalation in Patients With Pulmonary Arterial Hypertension (PAH)

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Iloprost (Ventavis inhaled, BAYQ6256)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged 18 to 75 years Symptomatic Pulmonary Artery Hypertension (PAH) classified (Dana Point Classification 1) New York Heart Association (NYHA)/World Health Organization (WHO) functional class III or IV PAPmean at rest > 25 mm Hg, Pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure </= 15 mm Hg and Pulmonary Vascular resistance (PVR) >/= 240 dyn.sec.cm-5 (>/= 400 dyn.sec.cm-5 for patients treated with both endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5i) ) as measured by Right Heart Catheter test Women of childbearing potential and men must agree to use adequate contraception when sexually active Exclusion Criteria: Baseline 6-minute walk distance of less than 100 meters or more than 500 meters Subjects with critical severe PAH Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio < 60% and/or Total Lung Capacity (TLC) < 70% predicted (especially at interstitial lung disease, TLC < 60% predicted) Clinically relevant obstructive lung disease (e.g. asthma or chronic obstructive pulmonary disease ) More than mild patchy interstitial lung disease on High Resolution Computerized Tomography (HRCT) History of left-sided heart disease Uncontrolled systemic hypertension as evidenced by systolic blood pressure >/= 160 mm Hg or diastolic blood pressure >/= 100 mm Hg on repeated measurement Systemic hypotension with systolic blood pressure < 85 mm Hg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Iloprost (Ventavis inhaled, BAYQ6256)<br>* 2.5 μg or 5.0 μg BAYQ6256 per inhalation session (Inhalation session is to be conducted 6 to 9 times per day with dosing intervals of at least 2 hours.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pulmonary vascular resistance (PVR) from screening (baseline) to week 12 (after inhalation) |  | At baseline and 12 weeks | 
| Number of participants with adverse events as a measure of safety and tolerability |  | Up to 52 weeks | 
| Area under the plasma concentration vs time curve from start of inhalation to infinity after single inhalation (AUC) |  | At baseline, 12 weeks, 52 weeks and over 52 weeks | 
| Maximum drug concentration in plasma after start of inhalation (Cmax) |  | Up to 12 weeks | 
| Number of participants with adverse events as a measure of safety and tolerability |  | Over 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Pulmonary vascular resistance index (PVRI) from baseline to week 12 |  | At baseline and 12 weeks | 
| Change of mean of pulmonary artery pressure from baseline to week 12 |  | At baseline and 12 weeks | 
| Change of systolic pulmonary artery pressure from baseline to week 12 |  | At baseline and 12 weeks | 
| Change of diastolic pulmonary artery pressure from baseline to week 12 |  | At baseline and 12 weeks | 
| Change in Mean right atrial pressure (RAPm) |  | At baseline and 12 weeks | 
| Change in Pulmonary capillary wedge pressure (PCWP) |  | At baseline and 12 weeks | 
| Change in Cardiac output (CO) |  | At baseline and 12 weeks | 
| Change in Mean arterial pressure (MAP) |  | At baseline and 12 weeks | 
| Change Mixed venous oxygen saturation (SVO2) |  | At baseline and 12 weeks | 
| Change in Systemic vascular resistance (SVR) |  | At baseline and 12 weeks | 
| Change in Systemic vascular resistance index (SVRI) |  | At baseline and 12 weeks | 
| Change in Cardiac index |  | At baseline and 12 weeks | 
| Change in 6-minute walking test (6MWT) |  | At baseline, 12 weeks and 52 weeks | 
| Change in Borg CR 10 Score |  | At baseline, 12 weeks and 52 weeks | 
| Change in New York Heart Association/ World Health Organization (NYHA/WHO) class |  | At baseline, 12 weeks, 52 weeks and over 52 weeks | 
| Change in N-terminal pro-B-type natriuretic peptide (NT-ProBNP) |  | At baseline, 12 weeks and 52 weeks | 
| Quality of life assessed by EQ-5D and Living with Pulmonary Hypertension (LPH) questionnaires |  | At baseline, 12 weeks and 52 weeks | 
| Time to clinical worsening during the study |  | At baseline, 12 weeks, 52 weeks and over 52 weeks | 
| Mortality during the study |  | At baseline, 12 weeks, 52 weeks and over 52 weeks | 
| Need for transplantation during the study |  | At baseline, 12 weeks, 52 weeks and over 52 weeks | 
| AUC from time start of inhalation to the last data point AUC(0-tlast) |  | Up to 12 weeks | 
| AUC divided by dose per kg body weight (AUCnorm) |  | Up to 12 weeks | 
| AUC divided by dose (μg) (AUC/D) |  | Up to 12 weeks | 
| Maximum drug concentration in plasma after start of inhalation divided by dose (μg) per kg body weight (Cmax,norm) |  | Up to 12 weeks | 
| Maximum drug concentration in plasma after start of inhalation divided by dose (μg) (Cmax/D) |  | Up to 12 weeks | 
| Time to reach maximum drug concentration in plasma after start of inhalation (tmax ) |  | Up to 12 weeks | 
| Half-life associated with the terminal slope (t1/2) |  | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iloprost, Inhalation, Pulmonary Hypertension, Pulmonary Artery Hypertension, Japanese Patients