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 Hypertensio
- Conditions
- -I270 Primary pulmonary hypertensionPrimary pulmonary hypertensionI270
- Registration Number
- PER-117-09
- Lead Sponsor
- PFIZER S.A.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 0
• Men or women, aged> 18 years. All women of childbearing age should use an appropriate contraceptive method (i.e., hormonal together with an intrauterine device or spermicide barrier methods) throughout the study and the four weeks following the termination of this. Other alternatives are sexual abstinence or that Your partner may be vasectomized. Urine and serum pregnancy tests performed on the selection and the urine pregnancy test at baseline should be negative. Women who have been surgically sterilized or have been postmenopausal for at least two years may be included in the study and do not need to use contraceptives.
• Subjects with idiopathic pulmonary arterial hypertension (HAPI) or family (HAPF)
• Subjects with a mean PAP (pulmonary arterial pressure)> 25 mmHg and a pulmonary capillary interlocking pressure (PECP) <15 mm Hg at rest.
• Informed consent document, signed and dated personally, indicating that the subject (or his legal representative) has been informed of all relevant aspects of the study.
• Subjects willing and able to meet scheduled visits, treatment plan, laboratory tests and other study procedures.
• Subjects with any form of pulmonary hypertension other than idiopathic (IPAH) or familial (FPAH) pulmonary arterial hypertension.
• Subjects receiving specific treatment for PAH including PDE5 inhibitors, endothelin receptor antagonists, prostanoids; nitrates or nitric oxide donors in any form (oral, sublingual, buccal, transdermal, inhalational or aerosols), or potent CYP3A4 inhibitors such as e.g. erythromycin, ketoconazole and itraconazole; protease inhibitors e.g. ritonavir and saquinavir; and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 30 days prior to randomization.
• Subjects using chronic arginine supplementation including HeartBar® (This must have been stopped for at least 30 days prior to randomization).
• Subjects who have had a change of dose or class of standard background therapy used for treatment of PAH (i.e. oxygen, calcium channel blockers, digoxin, diuretics) within 30 days prior to randomization. A change in the dose of oral anticoagulant therapy is acceptable.
• Subjects who undergo a large shift in altitude (e.g., live at altitude and shift to sea level) during 90 days prior to baseline and/or during the study period. A large shift is being defined as approximately 5000 feet or 1524 meters.
• Subjects with significant (regurgitation >2) valvular disease other than tricuspid regurgitation or pulmonary regurgitation. Subjects with previous surgical replacement of a valve may be eligible for entry into the study after consultation with a Pfizer study clinician provided the following conditions are satisfied: That there was no evidence of PAH secondary to valvular disease prior to surgery. The prosthetic valve is functioning normally on echocardiography. The valve replacement occurred at least one year prior to randomization.
• Subjects with restrictive or congestive cardiomyopathy.
• Subjects with symptomatic coronary artery disease.
• Subjects with acutely decompensated heart failure within 30 days prior to randomization.
• Subjects with LV ejection fraction of <45% or LV shortening fraction of <0.2 within three months prior to randomization.
• Subjects with systemic arterial hypotension with systolic arterial blood pressure <90 mm Hg at screening or baseline (supine or standing).
• Subjects with systemic arterial hypertension with systolic arterial blood pressure >140 mm Hg at screening or baseline (supine or standing).
• Subjects who have had a myocardial infarction or stroke within 6 months prior to randomization.
• Subjects with intracardiac shunts including subjects who have undergone atrial septostomy.
• Subjects with uncontrolled brady- or tachyarrhythmias, placement of pacemakers or implantable defibrillators <60 days prior to randomization.
• Pregnant or lactating women.
• Subjects with a history of pulmonary embolism verified or not excluded by ventilation/perfusion scan, angiogram or spiral chest CT scan.
• Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischemic optic neuropathy (NAION) or untreated proliferative diabetic retinopathy.
• Subjects with history of chronic lung diseases or restrictive lung disease (e.g. COPD or scleroderma) with impairment of lung function as defined by TLC<60% and/or FEV1 =80% within 30 days of randomization.
• Subjects with previous intolerance
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name: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.<br><br>Measure:Mean Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) Over 4 Hours Post Dose<br>Timepoints:Baseline, up to 4 hours post-dose on Day 1<br>
- Secondary Outcome Measures
Name Time Method