Comparative PK PD Study in PAH Patients (Fox vs. I-Neb)

• ClinicalTrials.gov Identifier: NCT02032836
• Recruitment Status: Completed
• Last Update Posted: September 26, 2018
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pulmonary Arterial Hypertension	Drug: lloprost(Ventavis,BAYQ6252, 20 µg/mL); Drug: lloprost(Ventavis,BAYQ6252, 10 µg/mL)	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 10, 2014
• Actual Primary Completion Date: January 7, 2015
• Actual Study Completion Date: September 29, 2017

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 :

1. 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 Measures :

1. Maximum change in systolic, diastolic and mean arterial blood pressure [ Time Frame: From baseline to multiple BP measurements within 2 hours after iloprost inhalation ]
2. 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 ]
3. 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 ]
4. AUC (area under the plasma concentration curve of BAYQ6256 from zero to infinity) [ Time Frame: Multiple timepoints up to 1 hour ]
5. 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 ]
6. 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 ]
7. half-life (associated with terminal slope) [ Time Frame: Multiple blood sampling within 60 minutes after Ventavis inhalation and subsequent iloprost bioanalytics ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Austria

Graz, Steiermark, Austria, 8036

Germany

München, Bayern, Germany, 80639

Würzburg, Bayern, Germany, 97067

Gießen, Hessen, Germany, 35392

Köln, Nordrhein-Westfalen, Germany, 50924

Hamburg, Germany, 20246

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

Click here to find results for studies related to Bayer Healthcare products. 

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02032836
• Other Study ID Numbers: 16483; 2013-002783-12 ( EudraCT Number )
• First Posted: January 10, 2014
• Last Update Posted: September 26, 2018
• Last Verified: September 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Hypertension, Pulmonary; Lung Diseases; Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Iloprost; Platelet Aggregation Inhibitors; Vasodilator Agents