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

Pfizer's Upjohn has merged with Mylan to form Viatris Inc.275 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

275

Conditions

Hypertension, Pulmonary

Interventions

sildenafilDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (68)

Pfizer Investigational Site

Birmingham, Alabama, United States

Pfizer Investigational Site

Birmingham, Alabama, United States

Pfizer Investigational Site

Birmingham, Alabama, United States

Pfizer Investigational Site

La Jolla, California, United States

Pfizer Investigational Site

La Jolla, California, United States

Outcomes

Primary Outcomes

Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test).

Time frame: Week 12

Secondary Outcomes

Change from baseline in mean pulmonary arterial pressure

Time frame: Week 12

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

Change from baseline in the BORG dyspnoea score

Time frame: Week 12

Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class

Time frame: Week 12

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

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

Patient overall preference assessment

Time frame: Week 12

Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension

Time frame: throughout the study

Change from baseline in hemodynamic parameters

Time frame: Week 12