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 ARTERIAL HYPERTENSION

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2008-003572-21-DE
• Date of registration: 24/09/2008
• Prospective Registration: Yes
• Primary sponsor: Pfizer Ltd.
• Public 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 ARTERIAL HYPERTENSION
• Scientific 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 ARTERIAL HYPERTENSION
• Date of first enrolment: 30/01/2009
• Target sample size: 79
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003572-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, Germany, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects of = 18 years of age. All women of childbearing potential have to use adequate contraception (i.e. hormonal in conjunction with intrauterine device or barrier methods with spermicide) throughout and for four weeks after completion of the study. Alternatively subjects may be celibate or their partner may have had a vasectomy.
The screening urine and serum pregnancy tests and the baseline urine pregnancy test must be negative. Women who have been surgically sterilized or are at least two years postmenopausal may be enrolled and do not need to use birth control.
2. Subjects with idiopathic (IPAH) or familial (FPAH)) pulmonary arterial hypertension.
3. Subjects with a mean PAP (pulmonary artery pressure) = 25mmHg and a pulmonary capillary wedge pressure (PCWP) of <15mmHg at rest.
4. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
5. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects with any form of pulmonary hypertension other than idiopathic (IPAH) or
familial (FPAH) pulmonary arterial hypertension.
2. Subjects receiving specific treatment for PAH including PDE5 inhibitors, endothelin
receptor antagonists, prostanoids; nitrates or nitric oxide donors in any form (oral,
sublingual, buccal, transdermal, inhalational or aerosols), or potent CYP3A4 inhibitors
such as e.g. erythromycin, ketoconazole and itraconazole; protease inhibitors e.g.
ritonavir and saquinavir; and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 30 days prior to randomization.
3. Subjects using chronic arginine supplementation including HeartBar® (This must have been stopped for at least 30 days prior to randomization).
4. Subjects who have had a change of dose or class of standard background therapy used for treatment of PAH (i.e. oxygen, calcium channel blockers, digoxin, diuretics) within 30 days prior to randomization. A change in the dose of oral anticoagulant therapy is acceptable.
5. Subjects who undergo a large shift in altitude (e.g., live at altitude and shift to sea level) during 90 days prior to baseline and/or during the study period. A large shift is being defined as approximately 5000 feet or 1524 meters.
6. Subjects with significant (regurgitation >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.
7. Subjects with restrictive or congestive cardiomyopathy.
8. Subjects with symptomatic coronary artery disease.
9. Subjects with acutely decompensated heart failure within 30 days prior to randomization.
10. Subjects with LV ejection fraction of <45% or LV shortening fraction of <0.2 within three months prior to randomization.
11. Subjects with systemic arterial hypotension with systolic arterial blood pressure <90 mm Hg at screening or baseline (supine or standing).
12. Subjects with systemic arterial hypertension with systolic arterial blood pressure >140 mm Hg at screening or baseline (supine or standing).
13. Subjects who have had a myocardial infarction or stroke within 6 months prior to
randomization.
14. Subjects with intracardiac shunts including subjects who have undergone atrial
septostomy.
15. Subjects with uncontrolled brady- or tachyarrhythmias, placement of pacemakers or implantable defibrillators <60 days prior to randomization.
16. Pregnant or lactating women.
17. Subjects with a history of pulmonary embolism verified or not excluded by ventilation/perfusion scan, angiogram or spiral CT scan.
18. Subjects with known hereditary degenerative retinal disorders (such as retinitis
pigmentosa) or history of non-arteritic anterior ischemic optic neuropathy (NAION) or
untreated proliferative diabetic retinopathy.
19. Subjects with history of chronic lung diseases or restrictive lung disease (e.g. COPD or scleroderma) with impairment of lung function as defined by TLC<60% and/or FEV1 =80% within 30 days of randomization.
20. Subjects with previous intolerance or allergy to PDE5 inhibitors or a history of mul

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary arterial hypertension.
MedDRA version: 9.1 Level: LLT Classification code 10064911 Term: Pulmonary arterial hypertension

Intervention(s)

Product Name: PF-00489791
Pharmaceutical Form: Film-coated tablet
CAS Number: 853003-48-2
Current Sponsor code: PF-00489791
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: PF-00489791
Pharmaceutical Form: Film-coated tablet
CAS Number: 853003-48-2
Current Sponsor code: PF-00489791
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: PF-00489791
Pharmaceutical Form: Film-coated tablet
CAS Number: 853003-48-2
Current Sponsor code: PF-00489791
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Revatio 20 mg Filmtabletten
Product Name: Sildenafil Filmtabletten
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sildenafil
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate the effect of different doses of PF-00489791 on systemic vascular resistance index (SVRI) and other systemic hemodynamic parameters.
To evaluate specificity of different doses of PF-00489791 for pulmonary vs. systemic
hemodynamics.
To evaluate the effect of different doses of PF-00489791 on cardiac index, mean PAP
and other pulmonary hemodynamic parameters and blood gases, assessed by right heart catheterization.
To evaluate safety of different doses of PF-00489791 after a single dose administration.
To characterize pharmacokinetics of PF-00489791 in subjects with PAH.

Main Objective: To evaluate the effect of different doses of PF-00489791 on PVRI in subjects with idiopathic and familial pulmonary arterial hypertension.

Primary end point(s): To evaluate the effect of different doses of PF-00489791 on PVRI in subjects with idiopathic and familial pulmonary arterial hypertension.

Secondary ID(s)

A7331009

2008-003572-21-SE