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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 27
- 主要终点
- 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
研究概览
简要总结
Administration of iloprost aerosol comparing two nebulizers: FOX and I-Neb
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: lloprost(Ventavis,BAYQ6252, 20 µg/mL) (Drug)
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.
干预措施: lloprost(Ventavis,BAYQ6252, 10 µg/mL) (Drug)
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.
干预措施: lloprost(Ventavis,BAYQ6252, 20 µg/mL) (Drug)
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.
干预措施: lloprost(Ventavis,BAYQ6252, 10 µg/mL) (Drug)
结局指标
主要结局
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
时间窗: multiple measurements within 30 minutes after iloprost inhalation
次要结局
- 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)