Pulmonary Arterial Hypertension MedDRA version: 9.1 Level: LLT Classification code 10064911 Term: Pulmonary arterial hypertension
Conditions
Interventions
Trade Name: Revatio
Product Name: Revatio®
Product Code: UK-92,480
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sildenafil
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Pfizer Ltd,Ramsgate Road,Sandwich CT13 9NJ
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects aged 18 and above at the time of the screening visit who have any of the following types of pulmonary arterial hypertension and functional class, and for which bosentan therapy is indicated according to EU Marketing Authorisation: · Idiopathic ‘Primary’ Pulmonary Arterial Hypertension (PAH) .Pulmonary Hypertension secondary to Scleroderma. ·Subjects with WHO functional class III prior to initiation of bosentan therapy. 2. Subjects must have been treated continually with a stable dose of bosentan (62.5mg bid or 125mg bid) for a minimum of three months prior to randomization. 3. Subject with a mean pulmonary artery pressure =25 mmHg and a pulmonary capillary wedge pressure 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. With the exception of bosentan therapy, subjects who are currently receiving any forms of chronic treatment for PAH such as any formulations of prostacyclin, PDE-5 inhibitors, other endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplements) including nicorandil in any form or any potent CYP3A4 inhibitors (e.g. Cyclosporin A and Glibenclamide). Note: Acute vasodilator response testing with any short acting vasodilators such as prostacyclin or inhaled NO during right heart catherization is permitted. 3. Subjects with significant (i.e. > 2+) 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 randomization. 4. Subjects with acutely decompensated heart failure within 30 days prior to randomization. 5. Subjects with LV Ejection Fraction of 2.5 X UpperLimits of Normal (ULN)). 19
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect on exercise capacity (as measured by the 6 Minute Walk Distance) after 12 weeks of treatment of sildenafil (20mg TID) or placebo when added to subjects with PAH who are stabilized on bosentan therapy;Secondary Objective: 1. To assess the safety and tolerability of sildenafil (20mg TID) or placebo, when added to subjects with PAH who are currently treated with bosentan, after 12 weeks of treatment. 2. To assess the safety and tolerability of the open label treatment of sildenafil (20mg TID) and bosentan therapy in subjects with PAH after 12 months of treatment. 3. To assess the effect on other clinical outcome measures (clinical worsening, Borg dyspnoea score and PAH functional class) after 12 weeks of treatment of sildenafil (20mg TID) or placebo when added to bosentan therapy in subjects with PAH. 4. To determine the population pharmacokinetic parameters of sildenafil and bosentan and to investigate potential pharmacokinetic interactions between the two compounds in the target patient population. 5. To investigate the PK/PD relationship between sildenafil and bosentan exposure on the 6-Minute Walk Test Tertiary Objective To investigate the effects on BNP and N-terminal pro-BNP;Primary end point(s): The change from baseline in the total distance walked during the 6-Minute Walk Test at Week 12 of the study. | — |
Countries
Czech Republic, Germany, Greece, Italy, United Kingdom
Outcome results
None listed