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

Primary Purpose

Hypertension, Pulmonary

Status

Completed

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

Iloprost (Ventavis inhaled, BAYQ6256)

About this trial

This is an interventional treatment trial for Hypertension, Pulmonary focused on measuring Iloprost, Inhalation, Pulmonary Hypertension, Pulmonary Artery Hypertension, Japanese Patients

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

Outcomes

Primary Outcome Measures

Change in Pulmonary vascular resistance (PVR) from screening (baseline) to week 12 (after inhalation)

Number of participants with adverse events as a measure of safety and tolerability

Area under the plasma concentration vs time curve from start of inhalation to infinity after single inhalation (AUC)

Maximum drug concentration in plasma after start of inhalation (Cmax)

Number of participants with adverse events as a measure of safety and tolerability

Secondary Outcome Measures

Change of Pulmonary vascular resistance index (PVRI) from baseline to week 12

Change of mean of pulmonary artery pressure from baseline to week 12

Change of systolic pulmonary artery pressure from baseline to week 12

Change of diastolic pulmonary artery pressure from baseline to week 12

Change in Mean right atrial pressure (RAPm)

Change in Pulmonary capillary wedge pressure (PCWP)

Change in Cardiac output (CO)

Change in Mean arterial pressure (MAP)

Change Mixed venous oxygen saturation (SVO2)

Change in Systemic vascular resistance (SVR)

Change in Systemic vascular resistance index (SVRI)

Change in Cardiac index

Change in 6-minute walking test (6MWT)

Change in Borg CR 10 Score

Change in New York Heart Association/ World Health Organization (NYHA/WHO) class

Change in N-terminal pro-B-type natriuretic peptide (NT-ProBNP)

Quality of life assessed by EQ-5D and Living with Pulmonary Hypertension (LPH) questionnaires

Time to clinical worsening during the study

Mortality during the study

Need for transplantation during the study

AUC from time start of inhalation to the last data point AUC(0-tlast)

AUC divided by dose per kg body weight (AUCnorm)

AUC divided by dose (μg) (AUC/D)

Maximum drug concentration in plasma after start of inhalation divided by dose (μg) per kg body weight (Cmax,norm)

Maximum drug concentration in plasma after start of inhalation divided by dose (μg) (Cmax/D)

Time to reach maximum drug concentration in plasma after start of inhalation (tmax )

Half-life associated with the terminal slope (t1/2)

Full Information

NCT ID

NCT01469169

First Posted

November 8, 2011

Last Updated

December 6, 2017

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT01469169

Brief Title

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

Acronym

IBUKI

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

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Completed

Study Start Date

June 19, 2012 (Actual)

Primary Completion Date

December 26, 2014 (Actual)

Study Completion Date

December 14, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypertension, Pulmonary

Keywords

Iloprost, Inhalation, Pulmonary Hypertension, Pulmonary Artery Hypertension, Japanese Patients

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Iloprost (Ventavis inhaled, BAYQ6256)

Intervention Description

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.)

Primary Outcome Measure Information:

Title

Change in Pulmonary vascular resistance (PVR) from screening (baseline) to week 12 (after inhalation)

Time Frame

At baseline and 12 weeks

Title

Number of participants with adverse events as a measure of safety and tolerability

Time Frame

Up to 52 weeks

Title

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

Title

Maximum drug concentration in plasma after start of inhalation (Cmax)

Time Frame

Up to 12 weeks

Title

Number of participants with adverse events as a measure of safety and tolerability

Time Frame

Over 52 weeks

Secondary Outcome Measure Information:

Title

Change of Pulmonary vascular resistance index (PVRI) from baseline to week 12

Time Frame

At baseline and 12 weeks

Title

Change of mean of pulmonary artery pressure from baseline to week 12

Time Frame

At baseline and 12 weeks

Title

Change of systolic pulmonary artery pressure from baseline to week 12

Time Frame

At baseline and 12 weeks

Title

Change of diastolic pulmonary artery pressure from baseline to week 12

Time Frame

At baseline and 12 weeks

Title

Change in Mean right atrial pressure (RAPm)

Time Frame

At baseline and 12 weeks

Title

Change in Pulmonary capillary wedge pressure (PCWP)

Time Frame

At baseline and 12 weeks

Title

Change in Cardiac output (CO)

Time Frame

At baseline and 12 weeks

Title

Change in Mean arterial pressure (MAP)

Time Frame

At baseline and 12 weeks

Title

Change Mixed venous oxygen saturation (SVO2)

Time Frame

At baseline and 12 weeks

Title

Change in Systemic vascular resistance (SVR)

Time Frame

At baseline and 12 weeks

Title

Change in Systemic vascular resistance index (SVRI)

Time Frame

At baseline and 12 weeks

Title

Change in Cardiac index

Time Frame

At baseline and 12 weeks

Title

Change in 6-minute walking test (6MWT)

Time Frame

At baseline, 12 weeks and 52 weeks

Title

Change in Borg CR 10 Score

Time Frame

At baseline, 12 weeks and 52 weeks

Title

Change in New York Heart Association/ World Health Organization (NYHA/WHO) class

Time Frame

At baseline, 12 weeks, 52 weeks and over 52 weeks

Title

Change in N-terminal pro-B-type natriuretic peptide (NT-ProBNP)

Time Frame

At baseline, 12 weeks and 52 weeks

Title

Quality of life assessed by EQ-5D and Living with Pulmonary Hypertension (LPH) questionnaires

Time Frame

At baseline, 12 weeks and 52 weeks

Title

Time to clinical worsening during the study

Time Frame

At baseline, 12 weeks, 52 weeks and over 52 weeks

Title

Mortality during the study

Time Frame

At baseline, 12 weeks, 52 weeks and over 52 weeks

Title

Need for transplantation during the study

Time Frame

At baseline, 12 weeks, 52 weeks and over 52 weeks

Title

AUC from time start of inhalation to the last data point AUC(0-tlast)

Time Frame

Up to 12 weeks

Title

AUC divided by dose per kg body weight (AUCnorm)

Time Frame

Up to 12 weeks

Title

AUC divided by dose (μg) (AUC/D)

Time Frame

Up to 12 weeks

Title

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

Title

Maximum drug concentration in plasma after start of inhalation divided by dose (μg) (Cmax/D)

Time Frame

Up to 12 weeks

Title

Time to reach maximum drug concentration in plasma after start of inhalation (tmax )

Time Frame

Up to 12 weeks

Title

Half-life associated with the terminal slope (t1/2)

Time Frame

Up to 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

City

Nagoya

State/Province

Aichi

ZIP/Postal Code

466-8560

Country

Japan

City

Nagoya

State/Province

Aichi

ZIP/Postal Code

467-8602

Country

Japan

City

Kurume

State/Province

Fukuoka

ZIP/Postal Code

830-0011

Country

Japan

City

Asahikwa

State/Province

Hokkaido

ZIP/Postal Code

078-8510

Country

Japan

City

Kobe

State/Province

Hyogo

ZIP/Postal Code

650-0017

Country

Japan

City

Kawasaki

State/Province

Kanagawa

ZIP/Postal Code

216-8511

Country

Japan

City

Sendai

State/Province

Miyagi

ZIP/Postal Code

980-8574

Country

Japan

City

Tomigusuku

State/Province

Okinawa

ZIP/Postal Code

901-0243

Country

Japan

City

Bunkyo-ku

State/Province

Tokyo

ZIP/Postal Code

113-8655

Country

Japan

City

Chuoku

State/Province

Tokyo

ZIP/Postal Code

104-8560

Country

Japan

City

Mitaka

State/Province

Tokyo

ZIP/Postal Code

181-8611

Country

Japan

City

Ota-ku

State/Province

Tokyo

ZIP/Postal Code

143-8541

Country

Japan

City

Shinjuku-ku

State/Province

Tokyo

ZIP/Postal Code

160-8582

Country

Japan

City

Shinjuku-ku

State/Province

Tokyo

ZIP/Postal Code

162-8655

Country

Japan

City

Tanabe

State/Province

Wakayama

ZIP/Postal Code

646-8558

Country

Japan

City

Ube

State/Province

Yamaguchi

ZIP/Postal Code

755-8505

Country

Japan

City

Chiba

ZIP/Postal Code

260-8677

Country

Japan

City

Tokushima

ZIP/Postal Code

770-8503

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

27001191

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.

Results Reference

result

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

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