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

Tracking Information
First Submitted Date ICMJE	November 8, 2011
First Posted Date ICMJE	November 10, 2011
Last Update Posted Date	December 7, 2017
Actual Study Start Date ICMJE	June 19, 2012
Actual Primary Completion Date	December 26, 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 6, 2017)	Change in Pulmonary vascular resistance (PVR) from screening (baseline) to week 12 (after inhalation) [ Time Frame: At baseline and 12 weeks ]; Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 52 weeks ]; Area under the plasma concentration vs time curve from start of inhalation to infinity after single inhalation (AUC) [ Time Frame: At baseline, 12 weeks, 52 weeks and over 52 weeks ]; Maximum drug concentration in plasma after start of inhalation (Cmax) [ Time Frame: Up to 12 weeks ]; Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Over 52 weeks ]
Original Primary Outcome Measures ICMJE; (submitted: November 8, 2011)	Change in Pulmonary vascular resistance (PVR) from screening (baseline) to week 12 (after inhalation) [ Time Frame: At baseline and 12 weeks ]
Change History	Complete list of historical versions of study NCT01469169 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 6, 2017)	Change of Pulmonary vascular resistance index (PVRI) from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]; Change of mean of pulmonary artery pressure from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]; Change of systolic pulmonary artery pressure from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]; Change of diastolic pulmonary artery pressure from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]; Change in Mean right atrial pressure (RAPm) [ Time Frame: At baseline and 12 weeks ]; Change in Pulmonary capillary wedge pressure (PCWP) [ Time Frame: At baseline and 12 weeks ]; Change in Cardiac output (CO) [ Time Frame: At baseline and 12 weeks ]; Change in Mean arterial pressure (MAP) [ Time Frame: At baseline and 12 weeks ]; Change Mixed venous oxygen saturation (SVO2) [ Time Frame: At baseline and 12 weeks ]; Change in Systemic vascular resistance (SVR) [ Time Frame: At baseline and 12 weeks ]; Change in Systemic vascular resistance index (SVRI) [ Time Frame: At baseline and 12 weeks ]; Change in Cardiac index [ Time Frame: At baseline and 12 weeks ]; Change in 6-minute walking test (6MWT) [ Time Frame: At baseline, 12 weeks and 52 weeks ]; Change in Borg CR 10 Score [ Time Frame: At baseline, 12 weeks and 52 weeks ]; Change in New York Heart Association/ World Health Organization (NYHA/WHO) class [ Time Frame: At baseline, 12 weeks, 52 weeks and over 52 weeks ]; Change in N-terminal pro-B-type natriuretic peptide (NT-ProBNP) [ Time Frame: At baseline, 12 weeks and 52 weeks ]; Quality of life assessed by EQ-5D and Living with Pulmonary Hypertension (LPH) questionnaires [ Time Frame: At baseline, 12 weeks and 52 weeks ]; Time to clinical worsening during the study [ Time Frame: At baseline, 12 weeks, 52 weeks and over 52 weeks ]; Mortality during the study [ Time Frame: At baseline, 12 weeks, 52 weeks and over 52 weeks ]; Need for transplantation during the study [ Time Frame: At baseline, 12 weeks, 52 weeks and over 52 weeks ]; AUC from time start of inhalation to the last data point AUC(0-tlast) [ Time Frame: Up to 12 weeks ]; AUC divided by dose per kg body weight (AUCnorm) [ Time Frame: Up to 12 weeks ]; AUC divided by dose (μg) (AUC/D) [ Time Frame: Up to 12 weeks ]; Maximum drug concentration in plasma after start of inhalation divided by dose (μg) per kg body weight (Cmax,norm) [ Time Frame: Up to 12 weeks ]; Maximum drug concentration in plasma after start of inhalation divided by dose (μg) (Cmax/D) [ Time Frame: Up to 12 weeks ]; Time to reach maximum drug concentration in plasma after start of inhalation (tmax ) [ Time Frame: Up to 12 weeks ]; Half-life associated with the terminal slope (t1/2) [ Time Frame: Up to 12 weeks ]
Original Secondary Outcome Measures ICMJE; (submitted: November 8, 2011)	Change of Pulmonary vascular resistance index (PVRI) from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]; Change of mean of pulmonary artery pressure from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]; Change of systolic pulmonary artery pressure from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]; Change of diastolic pulmonary artery pressure from baseline to week 12 [ Time Frame: At baseline and 12 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Inhaled Iloprost (Ventavis): Efficacy, Safety, and Pharmacokinetics (PK) Confirmation Study
Official Title ICMJE	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)
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Hypertension, Pulmonary
Intervention ICMJE	Drug: Iloprost (Ventavis inhaled, BAYQ6256); 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.)
Study Arms	Experimental: Arm 1; Intervention: Drug: Iloprost (Ventavis inhaled, BAYQ6256)
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 13, 2014)	27
Original Estimated Enrollment ICMJE; (submitted: November 8, 2011)	20
Actual Study Completion Date	December 14, 2016
Actual Primary Completion Date	December 26, 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 75 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Japan
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01469169
Other Study ID Numbers ICMJE	15503
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Not Provided
Responsible Party	Bayer
Study Sponsor ICMJE	Bayer
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Bayer Study Director Bayer
PRS Account	Bayer
Verification Date	December 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP