Clinical trial NCT02032836: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-01-10
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Administration of iloprost aerosol comparing two nebulizers: FOX and I-Neb


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

Primary outcomes:
measure: 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
timeFrame: multiple measurements within 30 minutes after iloprost inhalation
Secondary outcomes:
measure: Maximum change in systolic, diastolic and mean arterial blood pressure
timeFrame: From baseline to multiple BP measurements within 2 hours after iloprost inhalation
measure: Maximum change in heart rate within the 30 minutes following inhalation
timeFrame: From baseline to multiple HR measurements within 30 minutes after iloprost inhalation
measure: Maximum change in oxygen saturation within the 30 minutes following inhalation using finger pulse oxymetry
timeFrame: From baseline to multiple measurements within 30 minutes after iloprost inhalation
measure: AUC (area under the plasma concentration curve of BAYQ6256 from zero to infinity)
timeFrame: Multiple timepoints up to 1 hour
measure: Maximum observed drug concentration in plasma after single dose administration
timeFrame: Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics
measure: Time to reach maximum drug observed concentration in plasma after single dose
timeFrame: Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics
measure: half-life (associated with terminal slope)
timeFrame: Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics
Other outcomes:
Locations:
city: Graz
country: Austria
state: Steiermark
city: München
country: Germany
state: Bayern
city: Würzburg
country: Germany
state: Bayern
city: Gießen
country: Germany
state: Hessen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Hamburg
country: Germany
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: