A Phase 2a, Randomized, Double Blind, Placebo-controlled, Parallel Group Study Investigating The Dose-response Of Pf-00489791 On Acute Hemodynamics In Subjects With Idiopathic And Familial Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 48
- 试验地点
- 24
- 主要终点
- Mean Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) Over 4 Hours Post Dose
研究概览
简要总结
Study will assess PF-00489791 efficacy and safety in Pulmonary Arterial Hypertension (PAH)
详细描述
Pfizer decided to stop this trial early upon Stage 1 completion due to change in PF-00489791 development and not as a result of safety concerns for PF-00489791. Date of termination (LSLV) occurred on July 28, 2010.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Idiopathic or familial pulmonary arterial hypertension (PAH)
- •Mean PAP at least 25 mm Hg, PCWP < 15 mm Hg at rest
- •For females of child-bearing potential negative pregnancy test at screening and use of contraception during the study and 4 weeks after its completion
- •Signed and dated informed consent
- •Willingness to comply with the study plan and procedures
排除标准
- •pulmonary arterial hypertension (PAH)other than idiopathic or familial
- •For females, pregnancy or lactation
- •Use of specific PAH treatments, potent CYP3A4 inhibitors, protease inhibitors, alpha blockers or arginine 30 days prior tio randomization and during the study
- •Change of dose or class of standard background PAH therapy, i.e. oxygen, calcium channel blockers, digoxin, diuretics 30 days prior tio randomization and during the study
- •Large shift in altitude (defined as >5000 feet or 1524 meters) during 90 days prior to baseline visit and/or during the study visit
- •Subjects with intracardiac shunts and/or serious heart, lung or other health conditions
- •HIV positive subjects
- •Subjects participating in another clinical trial with an investigational drug or device
- •Subjects with degenerative retinal disorders, history of non-arteritic anterior ischemic optic neuropathy or untreated proliferative diabetic retinopathy
- •Allergies and previous intolerance of PDE5 inhibitors
- •Alcohol or drug abuse
- •Blood donation during the study, or 1 month before or after the study
研究组 & 干预措施
PF-00489791 1 mg
干预措施: PF-00489791 (Drug)
PF-00489791 2 mg
干预措施: PF-00489791 (Drug)
PF-00489791 4 mg
干预措施: PF-00489791 (Drug)
PF-00489791 10 mg
干预措施: PF-00489791 (Drug)
PF-00489791 20 mg
干预措施: PF-00489791 (Drug)
Placebo
干预措施: placebo (Drug)
Sildenafil
Observational comparator arm
干预措施: sildenafil (Drug)
结局指标
主要结局
Mean Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) Over 4 Hours Post Dose
时间窗: Baseline, up to 4 hours post-dose on Day 1
PVRI was calculated as: PVRI (in Wood units\*meter\^2 \[m\^2\]) = pulmonary vascular resistance (PVR) multiplied by body surface area (BSA). PVR (in Wood units) = (mean pulmonary artery pressure \[mean PAP\] minus pulmonary capillary wedge pressure \[PCWP\]) divided by cardiac output (CO, taken as the average of the triplicate measurements). BSA (m\^2) = (0.007184) multiplied by (height in centimeters \[cm\])\^0.725 multiplied by (weight in kilograms \[kg\])\^0.425. PVRI values were converted to dyne\*second (s)\*m\^2/centimeter (cm)\^5 from Woods units by multiplying by a factor of 79.9. The change from baseline in PVRI over 4-hour interval was calculated as the average of the change from baseline values at 1, 2, 3, and 4 hours post dose on Day 1.
次要结局
- Mean Change From Baseline in Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose(Baseline, up to 4 hours post-dose on Day 1)
- Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Values(Baseline up-to follow up (Day 3 to 5))
- Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP), Mean Systemic Arterial Pressure (SAP), Systolic Systemic Arterial Pressure (sSAP) and Diastolic Systemic Arterial Pressure (dSAP) at Hour 1, 2, 3 and 4 Post Dose(Baseline, 1, 2, 3, 4 hours post-dose on Day 1)
- Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) and Systemic Vascular Resistance (SVR) at Hour 1, 2, 3 and 4 Post Dose(Baseline, 1, 2, 3, 4 hours post-dose on Day 1)
- Greatest Reduction From Baseline in Pulmonary Vascular Resistance Index (PVRI) and Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose(Baseline, up to 4 hours post-dose on Day 1)
- Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Hour 1, 2, 3 and 4 Post Dose(Baseline, 1, 2, 3, 4 hours post-dose on Day 1)
- Change From Baseline in Mean Pulmonary Artery Pressure (mPAP), Systolic Pulmonary Artery Pressure (sPAP), Diastolic Pulmonary Artery Pressure (dPAP), Right Atrial Pressure (RAP) at Hour 1, 2, 3 and 4 Post Dose(Baseline, 1, 2, 3, 4 hours post-dose on Day 1)
- Change From Baseline in Cardiac Index (CI) at Hour 1, 2, 3 and 4 Post Dose(Baseline, 1, 2, 3, 4 hours post-dose on Day 1)
- Mean Change From Baseline in Heart Rate (HR) at Hour 1, 2, 3 and 4 Post Dose(Baseline, 1, 2, 3, 4 hours post-dose on Day 1)
- Change From Baseline in Mean Partial Pressure of Oxygen (PaO2) and Carbon Dioxide (PaCO2) at Hour 1 and 4 Post Dose(Baseline; 1, 4 hours post-dose on Day 1)
- Plasma Concentration of PF-00489791 and Sildenafil(1, 2, 3, 4, 5, 6, 8 hours post-dose on Day 1, follow up (Day 3 to 5))
- Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Hour 1, 2, 3 and 4 Post Dose(Baseline, 1, 2, 3, 4 hours post-dose on Day 1)
- Number of Participants With Clinically Significant Laboratory Values(Baseline up-to follow up (Day 3 to 5))