Clinical trial NCT00853112: A Research Study To Assess The Effectiveness And Safety Of Different Doses Of Oral PF-00489791 In The Treatment Of Adult Patients With Pulmonary Arterial Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hypertension, Pulmonary
Keywords: PAH pulmonary hypertension pulmonary arterial hypertension
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-03-02
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study will assess PF-00489791 efficacy and safety in Pulmonary Arterial Hypertension (PAH)

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Mean Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) Over 4 Hours Post Dose
timeFrame: Baseline, up to 4 hours post-dose on Day 1
Secondary outcomes:
measure: Greatest Reduction From Baseline in Pulmonary Vascular Resistance Index (PVRI) and Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose
timeFrame: Baseline, up to 4 hours post-dose on Day 1
measure: Mean Change From Baseline in Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose
timeFrame: Baseline, up to 4 hours post-dose on Day 1
measure: Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Hour 1, 2, 3 and 4 Post Dose
timeFrame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1
measure: Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Hour 1, 2, 3 and 4 Post Dose
timeFrame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1
measure: Change From Baseline in Cardiac Index (CI) at Hour 1, 2, 3 and 4 Post Dose
timeFrame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1
measure: 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
timeFrame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1
measure: 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
timeFrame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1
measure: Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) and Systemic Vascular Resistance (SVR) at Hour 1, 2, 3 and 4 Post Dose
timeFrame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1
measure: Mean Change From Baseline in Heart Rate (HR) at Hour 1, 2, 3 and 4 Post Dose
timeFrame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1
measure: Number of Participants With Clinically Significant Laboratory Values
timeFrame: Baseline up-to follow up (Day 3 to 5)
measure: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Values
timeFrame: Baseline up-to follow up (Day 3 to 5)
measure: Change From Baseline in Mean Partial Pressure of Oxygen (PaO2) and Carbon Dioxide (PaCO2) at Hour 1 and 4 Post Dose
timeFrame: Baseline; 1, 4 hours post-dose on Day 1
measure: Plasma Concentration of PF-00489791 and Sildenafil
timeFrame: 1, 2, 3, 4, 5, 6, 8 hours post-dose on Day 1, follow up (Day 3 to 5)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Phoenix
country: United States
facility: John C. Lincoln Hospital, North Mountain
state: Arizona
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Gainesville
country: United States
facility: Shands at University of Florida
state: Florida
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center - Department of Internal Medicine Pulmonary
state: Texas
city: Dallas
country: United States
facility: UT Southwestern St. Paul Hospital
state: Texas
city: London
country: Canada
facility: Lawson Health Research Institute
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis, Jewish General Hospital
state: Quebec
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitaetsklinikum
city: Hyderabad
country: India
facility: Department Of Cardiology, MediCiti Hospital,
state: Andhra Pardesh
city: Tirupati
country: India
facility: Department Of Cardiology, Sri Venkateswara Institute Of Medical Sciences
state: Andhra Pardesh
city: Vadodara
country: India
facility: Bankers Heart Institute
state: Gujarat
city: Mangalore
country: India
facility: Omega Hospital
state: Karnataka
city: Moscow
country: Russian Federation
facility: Moscow Healthcare Institution "City Clinical Hospital No. 57"
city: Moscow
country: Russian Federation
facility: Institute of Cardiosurgery n.a. V.I.Burakovsky
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall D´Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Lund
country: Sweden
facility: Universitetssjukhuset i Lund, Hjart- och Lungdivisionen
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus, Kliniskt Forsknings Centrum
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset, Kardiologen 50F/Forskningsenheten
city: Zuerich
country: Switzerland
facility: Universitaetsspittal Zuerich, Medizinische Klinik A
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: