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

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)

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.

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Drug: Iloprost (Ventavis inhaled, BAYQ6256)

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-8677
  • Tokushima, Japan, 770-8503
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
    • Nagoya, Aichi, Japan, 467-8602
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
  • Hokkaido
    • Asahikwa, Hokkaido, Japan, 078-8510
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0017
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
  • Okinawa
    • Tomigusuku, Okinawa, Japan, 901-0243
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
    • Chuoku, Tokyo, Japan, 104-8560
    • Mitaka, Tokyo, Japan, 181-8611
    • Ota-ku, Tokyo, Japan, 143-8541
    • Shinjuku-ku, Tokyo, Japan, 162-8655
    • Shinjuku-ku, Tokyo, Japan, 160-8582
  • Wakayama
    • Tanabe, Wakayama, Japan, 646-8558
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	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.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	Up to 52 weeks
Change in Pulmonary vascular resistance (PVR) from screening (baseline) to week 12 (after inhalation)	At baseline and 12 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	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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2012
• Primary Completion (Actual): December 26, 2014
• Study Completion (Actual): December 14, 2016

Study Registration Dates

• First Submitted: November 8, 2011
• First Submitted That Met QC Criteria: November 8, 2011
• First Posted (Estimate): November 10, 2011

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Iloprost; Japanese Patients; Inhalation; Pulmonary Artery Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: 15503

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No