A Study to Assess the Efficacy and Safety of 20, 40, and 80mg of Sildenafil Three Times a Day in the Treatment of Pulmonary Arterial Hypertension - Full Text View

Sponsor:	Pfizer
Information provided by:	Pfizer
ClinicalTrials.gov Identifier:	NCT00644605

Purpose

To evaluate the effect of three doses of oral sildenafil (20, 40 and 80 mg three times a day [TID]) on exercise capacity, as measured by the 6-Minute Walk test, as well as the safety and tolerability, after 12 weeks of treatment in subjects with pulmonary arterial hypertension who are aged 18 years and over. To investigate the plasma concentration-effect relationship and to determine the population pharmacokinetic (PK) parameters.

Condition	Intervention	Phase
Hypertension, Pulmonary	Drug: sildenafil Drug: placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title:	A Multinational, Multi-Centre, Randomised, Double-Blind, Double-Dummy, Placebo-Controlled Study to Assess the Efficacy and Safety of 20, 40, and 80mg TID Sildenafil in the Treatment of Pulmonary Arterial Hypertension in Subjects Aged 18 Years and Over

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: Exercise and Physical Fitness High Blood Pressure Pulmonary Hypertension

Drug Information available for: Sildenafil Sildenafil citrate

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test). [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline in mean pulmonary arterial pressure [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Time from randomisation to the first occurrence of clinical worsening (death or lung transplantation or hospitalisation due to pulmonary hypertension or initiation of prostacyclin therapy or initiation of bosentan therapy) [ Time Frame: Week 0 to 12 ] [ Designated as safety issue: No ]
Change from baseline in the BORG dyspnoea score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Change from baseline in the 8 dimensions of SF-36 (Physical functioning, Role functioning, Bodily pain, General health, Vitality, Social functioning, Mental health and Reported health transition) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
Change from baseline at Weeks 4 and 12 in the 5 dimensions of ED5Q (Mobility, Self care, Usual Activities, Pain/Discomfort and Anxiety/Depression) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
Patient overall preference assessment [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
Change from baseline in hemodynamic parameters [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment:	275
Study Start Date:	October 2002
Study Completion Date:	November 2003

Arms	Assigned Interventions
Arm 1: Active Comparator	Drug: sildenafil sildenafil 20 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Arm 2: Active Comparator	Drug: sildenafil sildenafil 40 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Arm 3: Active Comparator	Drug: sildenafil sildenafil 80 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks; initially, patients received 40mg TID for one week and were then up-titrated to 80mg TID
Arm 4: Placebo Comparator	Drug: placebo placebo by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Included patients had primary pulmonary arterial hypertension, pulmonary hypertension secondary to connective tissue disease, or pulmonary hypertension with surgical repair at least 5 years previously; a mean pulmonary artery pressure greater than or equal to 25 mmHg and a pulmonary artery wedge pressure of less than or equal to 15 mmHg at rest, via right heart catheterisation within 21 days prior to randomisation; and a baseline 6-Minute Walk test distance of 100 m to 450 m.

Exclusion Criteria:

Subjects with congenital heart disease, pulmonary hypertension due to thromboembolism, HIV, chronic obstructive airway disease, congestive heart failure or schistosomiasis; subjects with significant (ie > 2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation; and acutely decompensated heart failure within the previous 30 days; subjects with pulmonary hypertension secondary to any other etiology other than those specified in the inclusion criteria.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00644605

Show 68 Study Locations

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer, Inc. ( Director, Clinical Trial Disclosure Group )
Study ID Numbers:	A1481140
Study First Received:	March 20, 2008
Last Updated:	March 31, 2008
ClinicalTrials.gov Identifier:	NCT00644605 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Vasodilator Agents
Molecular Mechanisms of Pharmacological Action
Vascular Diseases
Sildenafil
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions

Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Hypertension, Pulmonary
Lung Diseases
Therapeutic Uses
Cardiovascular Diseases
Hypertension

ClinicalTrials.gov processed this record on November 25, 2009