Pulmonary arterial hypertension (PAH). MedDRA version: 8.1 Level: LLT Classification code 10037400 Term: Pulmonary hypertension
Conditions
Interventions
Trade Name: Revatio
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sildenafil citrate
Other descriptive name: UK-92,480
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Pfizer Ltd. Ramsgate Road, Sandwich, Kent, UK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects aged 18 and over with any of the following conditions: • Idiopathic Primary Pulmonary Arterial Hypertension (IPAH) • PAH secondary to connective tissue disease • PAH with surgical repair (at least 5 years previously) of atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA) and aorto-pulmonary window 2. Subjects with a mean pulmonary artery pressure of greater than or equal to 25 mmHg and a pulmonary artery wedge pressure of less than or equal to 15 mmHg at rest (or in the event that PAWP is unobtainable, a left ventricular end diastolic pressure (LVEDP) of =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. PAH secondary to any aetiology including congenital heart disease other than those specified in the inclusion criteria. 2. Subjects with significant 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 screening. 3. Subjects who have undergone atrial septostomy within 6 months prior to randomization. 4. Subjects with acutely decompensated heart failure within the previous 30 days prior to screening. 5. Subjects with a left ventricular ejection fraction (LVEF) less than 40% or LV shortening fraction 2.5 mg/dL (>220 µmol/L)). This criterion may be satisfied by a creatinine result from the clinic’s local laboratory. 17. Subjects with hypotension defined as systolic arterial pressure <90 mmHg after sitting for 5 minutes at either screening or baseline. 18. Subjects with severe impairment of hepatic function, Child-P
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.;Secondary Objective: • To assess the safety and tolerability of sildenafil (1 mg, 5 mg and 20 mg TID) after 12 weeks of treatment in subjects with PAH. • To evaluate the effects of sildenafil (1 mg, 5 mg and 20 mg TID) on biomarkers of progression of PAH as measured by B-type natriuretic peptide (BNP)/pro-BNP levels and tricuspid annular plane systolic excursion (TAPSE) • To determine the population pharmacokinetic parameters, and assess potential relationship of 6MWD, BNP/pro-BNP, TAPSE, PVRI and sildenafil exposure.;Primary end point(s): The change from baseline in the total distance walked during the 6MWT at Week 12 of the study | — |
Countries
Belgium, Bulgaria, Denmark, Greece, Italy, Latvia, Netherlands, United Kingdom
Outcome results
None listed