Clinical trial NCT01469169: Inhaled Iloprost (Ventavis): Efficacy, Safety, and Pharmacokinetics (PK) Confirmation Study
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension, Pulmonary
Keywords: Iloprost
Inhalation
Pulmonary Hypertension
Pulmonary Artery Hypertension
Japanese Patients
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2011-11-10
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Pulmonary vascular resistance (PVR) from screening (baseline) to week 12 (after inhalation)
timeFrame: At baseline and 12 weeks
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Up to 52 weeks
measure: Area under the plasma concentration vs time curve from start of inhalation to infinity after single inhalation (AUC)
timeFrame: At baseline, 12 weeks, 52 weeks and over 52 weeks
measure: Maximum drug concentration in plasma after start of inhalation (Cmax)
timeFrame: Up to 12 weeks
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Over 52 weeks
Secondary outcomes:
measure: Change of Pulmonary vascular resistance index (PVRI) from baseline to week 12
timeFrame: At baseline and 12 weeks
measure: Change of mean of pulmonary artery pressure from baseline to week 12
timeFrame: At baseline and 12 weeks
measure: Change of systolic pulmonary artery pressure from baseline to week 12
timeFrame: At baseline and 12 weeks
measure: Change of diastolic pulmonary artery pressure from baseline to week 12
timeFrame: At baseline and 12 weeks
measure: Change in Mean right atrial pressure (RAPm)
timeFrame: At baseline and 12 weeks
measure: Change in Pulmonary capillary wedge pressure (PCWP)
timeFrame: At baseline and 12 weeks
measure: Change in Cardiac output (CO)
timeFrame: At baseline and 12 weeks
measure: Change in Mean arterial pressure (MAP)
timeFrame: At baseline and 12 weeks
measure: Change Mixed venous oxygen saturation (SVO2)
timeFrame: At baseline and 12 weeks
measure: Change in Systemic vascular resistance (SVR)
timeFrame: At baseline and 12 weeks
measure: Change in Systemic vascular resistance index (SVRI)
timeFrame: At baseline and 12 weeks
measure: Change in Cardiac index
timeFrame: At baseline and 12 weeks
measure: Change in 6-minute walking test (6MWT)
timeFrame: At baseline, 12 weeks and 52 weeks
measure: Change in Borg CR 10 Score
timeFrame: At baseline, 12 weeks and 52 weeks
measure: Change in New York Heart Association/ World Health Organization (NYHA/WHO) class
timeFrame: At baseline, 12 weeks, 52 weeks and over 52 weeks
measure: Change in N-terminal pro-B-type natriuretic peptide (NT-ProBNP)
timeFrame: At baseline, 12 weeks and 52 weeks
measure: Quality of life assessed by EQ-5D and Living with Pulmonary Hypertension (LPH) questionnaires
timeFrame: At baseline, 12 weeks and 52 weeks
measure: Time to clinical worsening during the study
timeFrame: At baseline, 12 weeks, 52 weeks and over 52 weeks
measure: Mortality during the study
timeFrame: At baseline, 12 weeks, 52 weeks and over 52 weeks
measure: Need for transplantation during the study
timeFrame: At baseline, 12 weeks, 52 weeks and over 52 weeks
measure: AUC from time start of inhalation to the last data point AUC(0-tlast)
timeFrame: Up to 12 weeks
measure: AUC divided by dose per kg body weight (AUCnorm)
timeFrame: Up to 12 weeks
measure: AUC divided by dose (μg) (AUC/D)
timeFrame: Up to 12 weeks
measure: Maximum drug concentration in plasma after start of inhalation divided by dose (μg) per kg body weight (Cmax,norm)
timeFrame: Up to 12 weeks
measure: Maximum drug concentration in plasma after start of inhalation divided by dose (μg) (Cmax/D)
timeFrame: Up to 12 weeks
measure: Time to reach maximum drug concentration in plasma after start of inhalation (tmax )
timeFrame: Up to 12 weeks
measure: Half-life associated with the terminal slope (t1/2)
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Nagoya
country: Japan
state: Aichi
city: Nagoya
country: Japan
state: Aichi
city: Kurume
country: Japan
state: Fukuoka
city: Asahikwa
country: Japan
state: Hokkaido
city: Kobe
country: Japan
state: Hyogo
city: Kawasaki
country: Japan
state: Kanagawa
city: Sendai
country: Japan
state: Miyagi
city: Tomigusuku
country: Japan
state: Okinawa
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Chuoku
country: Japan
state: Tokyo
city: Mitaka
country: Japan
state: Tokyo
city: Ota-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Tanabe
country: Japan
state: Wakayama
city: Ube
country: Japan
state: Yamaguchi
city: Chiba
country: Japan
city: Tokushima
country: Japan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Saji T, Myoishi M, Sugimura K, Tahara N, Takeda Y, Fukuda K, Olschewski H, Matsuda Y, Nikkho S, Satoh T. Efficacy and Safety of Inhaled Iloprost in Japanese Patients With Pulmonary Arterial Hypertension - Insights From the IBUKI and AIR Studies. Circ J. 2016;80(4):835-42. doi: 10.1253/circj.CJ-16-0097. Epub 2016 Mar 18.