Comparative PK PD Study in PAH Patients (Fox vs. I-Neb)
Study Details
Study Description
Brief Summary
Administration of iloprost aerosol comparing two nebulizers: FOX and I-Neb
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: I-Neb - FOX 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. |
Drug: lloprost(Ventavis,BAYQ6252, 20 µg/mL)
20 µg/mL iloprost nebulizer solution, inhaled with FOX nebulizer
Drug: lloprost(Ventavis,BAYQ6252, 10 µg/mL)
10 µg/mL iloprost nebulizer solution, inhaled with I-Neb nebulizer
|
| Experimental: FOX - I-Neb 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. |
Drug: lloprost(Ventavis,BAYQ6252, 20 µg/mL)
20 µg/mL iloprost nebulizer solution, inhaled with FOX nebulizer
Drug: lloprost(Ventavis,BAYQ6252, 10 µg/mL)
10 µg/mL iloprost nebulizer solution, inhaled with I-Neb nebulizer
|
Outcome Measures
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 [multiple measurements within 30 minutes after iloprost inhalation]
Secondary Outcome Measures
- Maximum change in systolic, diastolic and mean arterial blood pressure [From baseline to multiple BP measurements within 2 hours after iloprost inhalation]
- Maximum change in heart rate within the 30 minutes following inhalation [From baseline to multiple HR measurements within 30 minutes after iloprost inhalation]
- Maximum change in oxygen saturation within the 30 minutes following inhalation using finger pulse oxymetry [From baseline to multiple measurements within 30 minutes after iloprost inhalation]
- AUC (area under the plasma concentration curve of BAYQ6256 from zero to infinity) [Multiple timepoints up to 1 hour]
- Maximum observed drug concentration in plasma after single dose administration [Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics]
- Time to reach maximum drug observed concentration in plasma after single dose [Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics]
- half-life (associated with terminal slope) [Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics]
Eligibility Criteria
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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Graz | Steiermark | Austria | 8036 | |
| 2 | München | Bayern | Germany | 80639 | |
| 3 | Würzburg | Bayern | Germany | 97067 | |
| 4 | Gießen | Hessen | Germany | 35392 | |
| 5 | Köln | Nordrhein-Westfalen | Germany | 50924 | |
| 6 | Hamburg | Germany | 20246 |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 16483
- 2013-002783-12