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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00853112
First received: February 27, 2009
Last updated: March 27, 2012
Last verified: March 2012
  Purpose

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


Condition Intervention Phase
Hypertension, Pulmonary
Drug: PF-00489791
Drug: placebo
Drug: sildenafil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Hypertension

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Mean change from baseline in PVRI [ Time Frame: Day 1, 4 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hourly changes from baseline in cardiac index, mean PAP and other hemodynamic parameters [ Time Frame: Day 1, up to 4 hours post dose ] [ Designated as safety issue: No ]
  • Changes from baseline in PaO2 and PaCO2 [ Time Frame: Day 1, up to 4 hours post dose ] [ Designated as safety issue: Yes ]
  • Plasma concentrations of PF-00489791 and sildenafil [ Time Frame: up to Day 3 - 5 ] [ Designated as safety issue: No ]
  • Safety and tolerability of PF-00489791 after a single dose administration as assessed by incidence of treatment-emergent adverse events, changes from baseline in clinical laboratory tests, and ECG [ Time Frame: up to Day 3 - 5 ] [ Designated as safety issue: Yes ]
  • Greatest reduction and hourly changes from baseline in PVRI [ Time Frame: Day 1, up to 4 hours post dose ] [ Designated as safety issue: No ]
  • Mean change, greatest reduction and hourly changes from baseline in SVRI [ Time Frame: Day 1, up to 4 hours post dose ] [ Designated as safety issue: No ]
  • Safety and tolerability of PF-00489791 after a single dose administration as assessed by incidence of treatment-emergent adverse events [ Time Frame: up to Day 10 - 14 ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: April 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-00489791 1 mg Drug: PF-00489791
tablet form, 1 mg, single dose (Day 1)
Experimental: PF-00489791 2 mg Drug: PF-00489791
tablet form, 2 mg, single dose (Day 1)
Experimental: PF-00489791 4 mg Drug: PF-00489791
tablet form, 4 mg, single dose (Day 1)
Experimental: PF-00489791 10 mg Drug: PF-00489791
tablet form, 10 mg, single dose (Day 1)
Experimental: PF-00489791 20 mg Drug: PF-00489791
tablet form, 20 mg, single dose (Day 1)
Placebo Comparator: Placebo Drug: placebo
tablet form, single dose (Day 1)
Active Comparator: Sildenafil
Observational comparator arm
Drug: sildenafil
tablet form, 20 mg, single dose (Day 1)
Other Name: Revatio

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853112

Locations
United States, Arizona
Pfizer Investigational Site
Phoenix, Arizona, United States, 85006
Pfizer Investigational Site
Phoenix, Arizona, United States, 85020
United States, Florida
Pfizer Investigational Site
Gainesville, Florida, United States, 32610
United States, Nebraska
Pfizer Investigational Site
Omaha, Nebraska, United States, 68131
United States, Pennsylvania
Pfizer Investigational Site
Pittsburgh, Pennsylvania, United States, 15212
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75390
Canada, Ontario
Pfizer Investigational Site
London, Ontario, Canada, N6A 4G5
Pfizer Investigational Site
London, Ontario, Canada, N6A 5A5
Pfizer Investigational Site
London, Ontario, Canada, N6A 5W9
Canada, Quebec
Pfizer Investigational Site
Montreal, Quebec, Canada, H3T 1E2
Germany
Pfizer Investigational Site
Heidelberg, Germany, 69126
India
Pfizer Investigational Site
Hyderabad, Andhra Pardesh, India, 500 063
Pfizer Investigational Site
Tirupati, Andhra Pardesh, India, 517 507
Pfizer Investigational Site
Vadodara, Gujarat, India, 390 015
Pfizer Investigational Site
Mangalore, Karnataka, India, 575 002
Russian Federation
Pfizer Investigational Site
Moscow, Russian Federation, 121552
Pfizer Investigational Site
Moscow, Russian Federation, 105077
Spain
Pfizer Investigational Site
Barcelona, Spain, 08035
Pfizer Investigational Site
Barcelona, Spain, 08036
Pfizer Investigational Site
Madrid, Spain, 28041
Sweden
Pfizer Investigational Site
Lund, Sweden, 221 85
Pfizer Investigational Site
Umea, Sweden, 901 85
Pfizer Investigational Site
Uppsala, Sweden, 751 85
Switzerland
Pfizer Investigational Site
Zuerich, Switzerland, CH-8091
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00853112     History of Changes
Other Study ID Numbers: A7331009
Study First Received: February 27, 2009
Last Updated: March 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
PAH pulmonary hypertension pulmonary arterial hypertension

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014