Back to resultsComparative PK PD Study in PAH Patients (Fox vs. I-Neb)
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
lloprost(Ventavis,BAYQ6252, 20 µg/mL)
lloprost(Ventavis,BAYQ6252, 10 µg/mL)
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility Criteria
Inclusion Criteria:
- Male or female aged ≥ 18 years
- Current diagnosis of pulmonary hypertension (updated Dana Point Classification 1).
- Current inhalative therapy with 5 µg iloprost using the I-Neb nebulizer
- WHO functional class III at the time of the patient's commencement of inhalative therapy with iloprost
- Hemodynamic diagnosis of Pulmonary arterial hypertension(PAH) showing mean pulmonary arterial pressure (mPAP) > 25 mmHg, pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) < 15 mmHg and pulmonary vascular resistance (PVR) > 320 dyn•s•cm-5
- If non-specific types of chronic treatment for PAH are being administered: Stable dosage of these for at least the 4 weeks up to screening
- If PAH-specific drug treatments (such as endothelin receptor antagonist (ERA) or phosphodiesterase-5 (PDE5) inhibitors) are being administered: Stable dosage of these for at least the 3 months up to screening.
Exclusion Criteria:
- PAH related to any other etiology, especially to pulmonary veno-occlusive disease (PVOD)
- Clinically relevant obstructive lung disease
- Evidence of thromboembolic disease (probable pulmonary embolism) within 3 years before screening
- Cerebrovascular events within 3 months before screening
- Atrial septostomy within the 6 months before screening
- Severe arrhythmia, or severe coronary heart disease or unstable angina, or myocardial infarction within 6 months before screening, or congenital or acquired valvular defects with clinically relevant myocardial function disorders unrelated to PAH
- Systolic blood pressure < 85 mm Hg, or uncontrolled systemic hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg)
- Hepatic impairment (Child Pugh B, C) or chronic renal insufficiency (creatinine > 2.5 mg/dl) and /or requirement of dialysis
- Clinically relevant bleedings disorders or conditions with increased risk for hemorrhages (active ulcers, trauma etc.)
- Addition or dose change of PAH specific drug treatments such as ERA or PDE5 inhibitors within 3 months before screening, or addition or dose change of non-specific treatments for PAH such as calcium channel blockers, nitrates, digitalis, diuretics within 4 weeks before Screening, or any kind of prostanoid other than those mentioned in inclusion criteria within less than 5 half-lives before treatment
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
I-Neb - FOX
FOX - I-Neb
Arm Description
Part 1: Subjects received single inhalation of 1.25 mcg iloprost using 10 mcg/ml iloprost solution (Ventavis 10) and then 2.5 mcg iloprost using Ventavis 10, both using the FOX nebulizer on Day 1. Part 2: On Day 2, subjects received single inhalation of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer; followed by single inhalation of 5 mcg iloprost using 20 mcg/ml iloprost solution (Ventavis 20) with the FOX nebulizer in a cross-over fashion. A washout period of at least 2 hours was maintained between treatments in Part 1 and Part 2. Part 3: Continued on Day 2, and through until Day 30, subjects received multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer for 2 weeks; followed by multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 20 with the FOX nebulizer for 2 weeks in a cross-over fashion.
Part 1: Subjects received single inhalation of 1.25 mcg iloprost using 10 mcg/ml iloprost solution (Ventavis 10) and then 2.5 mcg iloprost using Ventavis 10, both using the FOX nebulizer on Day 1. Part 2: On Day 2, subjects received single inhalation of 5 mcg iloprost using 20 mcg/ml iloprost solution (Ventavis 20) with the FOX nebulizer; followed by single inhalation of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer in a cross-over fashion. A wash-out period of at least 2 hours was maintained between treatments in Part 1 and Part 2. Part 3: Continued on Day 2, and through until Day 30, subjects received multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 20 with the FOX nebulizer for 2 weeks; followed by multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer for 2 weeks in a cross-over fashion.
Outcomes
Primary Outcome Measures
The proportion of patients with a meaningful maximum increase (i.e. >=25%) in heart rate AND/OR a meaningful maximum decrease (i.e. >=20%) in systolic blood pressure within the 30 minutes after the start of inhalation
Secondary Outcome Measures
Maximum change in systolic, diastolic and mean arterial blood pressure
Maximum change in heart rate within the 30 minutes following inhalation
Maximum change in oxygen saturation within the 30 minutes following inhalation using finger pulse oxymetry
AUC (area under the plasma concentration curve of BAYQ6256 from zero to infinity)
Maximum observed drug concentration in plasma after single dose administration
Time to reach maximum drug observed concentration in plasma after single dose
half-life (associated with terminal slope)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02032836
Brief Title
Comparative PK PD Study in PAH Patients (Fox vs. I-Neb)
Official Title
A Multi-center, Open-label, Randomized Cross-over Study to Compare the Acute Tolerability and Pharmacokinetics of BAYQ6256 (Iloprost; Ventavis) Inhalation Using the I-Neb Nebulizer and the FOX Nebulizer in Patients With Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
March 10, 2014 (Actual)
Primary Completion Date
January 7, 2015 (Actual)
Study Completion Date
September 29, 2017 (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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Administration of iloprost aerosol comparing two nebulizers: FOX and I-Neb
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
I-Neb - FOX
Arm Type
Experimental
Arm Description
Part 1: Subjects received single inhalation of 1.25 mcg iloprost using 10 mcg/ml iloprost solution (Ventavis 10) and then 2.5 mcg iloprost using Ventavis 10, both using the FOX nebulizer on Day 1. Part 2: On Day 2, subjects received single inhalation of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer; followed by single inhalation of 5 mcg iloprost using 20 mcg/ml iloprost solution (Ventavis 20) with the FOX nebulizer in a cross-over fashion. A washout period of at least 2 hours was maintained between treatments in Part 1 and Part 2. Part 3: Continued on Day 2, and through until Day 30, subjects received multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer for 2 weeks; followed by multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 20 with the FOX nebulizer for 2 weeks in a cross-over fashion.
Arm Title
FOX - I-Neb
Arm Type
Experimental
Arm Description
Part 1: Subjects received single inhalation of 1.25 mcg iloprost using 10 mcg/ml iloprost solution (Ventavis 10) and then 2.5 mcg iloprost using Ventavis 10, both using the FOX nebulizer on Day 1. Part 2: On Day 2, subjects received single inhalation of 5 mcg iloprost using 20 mcg/ml iloprost solution (Ventavis 20) with the FOX nebulizer; followed by single inhalation of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer in a cross-over fashion. A wash-out period of at least 2 hours was maintained between treatments in Part 1 and Part 2. Part 3: Continued on Day 2, and through until Day 30, subjects received multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 20 with the FOX nebulizer for 2 weeks; followed by multiple inhalations (approximately 6 to 9 inhalations per day) of 5 mcg iloprost using Ventavis 10 with the I-Neb nebulizer for 2 weeks in a cross-over fashion.
Intervention Type
Drug
Intervention Name(s)
lloprost(Ventavis,BAYQ6252, 20 µg/mL)
Intervention Description
20 µg/mL iloprost nebulizer solution, inhaled with FOX nebulizer
Intervention Type
Drug
Intervention Name(s)
lloprost(Ventavis,BAYQ6252, 10 µg/mL)
Intervention Description
10 µg/mL iloprost nebulizer solution, inhaled with I-Neb nebulizer
Primary Outcome Measure Information:
Title
The proportion of patients with a meaningful maximum increase (i.e. >=25%) in heart rate AND/OR a meaningful maximum decrease (i.e. >=20%) in systolic blood pressure within the 30 minutes after the start of inhalation
Time Frame
multiple measurements within 30 minutes after iloprost inhalation
Secondary Outcome Measure Information:
Title
Maximum change in systolic, diastolic and mean arterial blood pressure
Time Frame
From baseline to multiple BP measurements within 2 hours after iloprost inhalation
Title
Maximum change in heart rate within the 30 minutes following inhalation
Time Frame
From baseline to multiple HR measurements within 30 minutes after iloprost inhalation
Title
Maximum change in oxygen saturation within the 30 minutes following inhalation using finger pulse oxymetry
Time Frame
From baseline to multiple measurements within 30 minutes after iloprost inhalation
Title
AUC (area under the plasma concentration curve of BAYQ6256 from zero to infinity)
Time Frame
Multiple timepoints up to 1 hour
Title
Maximum observed drug concentration in plasma after single dose administration
Time Frame
Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics
Title
Time to reach maximum drug observed concentration in plasma after single dose
Time Frame
Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics
Title
half-life (associated with terminal slope)
Time Frame
Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female aged ≥ 18 years
Current diagnosis of pulmonary hypertension (updated Dana Point Classification 1).
Current inhalative therapy with 5 µg iloprost using the I-Neb nebulizer
WHO functional class III at the time of the patient's commencement of inhalative therapy with iloprost
Hemodynamic diagnosis of Pulmonary arterial hypertension(PAH) showing mean pulmonary arterial pressure (mPAP) > 25 mmHg, pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) < 15 mmHg and pulmonary vascular resistance (PVR) > 320 dyn•s•cm-5
If non-specific types of chronic treatment for PAH are being administered: Stable dosage of these for at least the 4 weeks up to screening
If PAH-specific drug treatments (such as endothelin receptor antagonist (ERA) or phosphodiesterase-5 (PDE5) inhibitors) are being administered: Stable dosage of these for at least the 3 months up to screening.
Exclusion Criteria:
PAH related to any other etiology, especially to pulmonary veno-occlusive disease (PVOD)
Clinically relevant obstructive lung disease
Evidence of thromboembolic disease (probable pulmonary embolism) within 3 years before screening
Cerebrovascular events within 3 months before screening
Atrial septostomy within the 6 months before screening
Severe arrhythmia, or severe coronary heart disease or unstable angina, or myocardial infarction within 6 months before screening, or congenital or acquired valvular defects with clinically relevant myocardial function disorders unrelated to PAH
Systolic blood pressure < 85 mm Hg, or uncontrolled systemic hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg)
Hepatic impairment (Child Pugh B, C) or chronic renal insufficiency (creatinine > 2.5 mg/dl) and /or requirement of dialysis
Clinically relevant bleedings disorders or conditions with increased risk for hemorrhages (active ulcers, trauma etc.)
Addition or dose change of PAH specific drug treatments such as ERA or PDE5 inhibitors within 3 months before screening, or addition or dose change of non-specific treatments for PAH such as calcium channel blockers, nitrates, digitalis, diuretics within 4 weeks before Screening, or any kind of prostanoid other than those mentioned in inclusion criteria within less than 5 half-lives before treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Graz
State/Province
Steiermark
ZIP/Postal Code
8036
Country
Austria
City
München
State/Province
Bayern
ZIP/Postal Code
80639
Country
Germany
City
Würzburg
State/Province
Bayern
ZIP/Postal Code
97067
Country
Germany
City
Gießen
State/Province
Hessen
ZIP/Postal Code
35392
Country
Germany
City
Köln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50924
Country
Germany
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
12. IPD Sharing Statement
Links:
URL
https://clinicaltrials.bayer.com/
Description
Click here to find results for studies related to Bayer Healthcare products.
Learn more about this trial
Comparative PK PD Study in PAH Patients (Fox vs. I-Neb)
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