A multi-centre, multinational, open-label single-dose acute hemodynamic study followed by a multi-centre, multinational, randomized, double-blind, parallel-group, placebo controlled study to assess the safety, tolerability, pharmacokinetics and preliminary efficacy (proof-of-concept) of ACT-293987 (NS-304) in the treatment of pulmonary arterial hypertension in subjects aged 18 years and over

• Conditions: pulmonary arterial hypertension (PAH) (idiopathic PAH, familial PAH, and PAH associated with collagen disease, corrected congenital vitium or anorexigen use); MedDRA version: 9.1Level: LLTClassification code 10065151Term: Idiopathic pulmonary arterial hypertension; MedDRA version: 9.1Level: LLTClassification code 10065152Term: Familial pulmonary arterial hypertension; MedDRA version: 9.1Level: LLTClassification code 10065150Term: Associated with pulmonary arterial hypertension; MedDRA version: 9.1Level: LLTClassification code 10064911Term: Pulmonary arterial hypertension

• Registration Number: EUCTR2007-003328-39-BE
• Lead Sponsor: Actelion Pharmaceuticals Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11-27
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1.Male and female subjects 18 years of age or older with symptomatic PAH despite treatment with anticoagulants, calcium channel blockers, diuretics, cardiac glycosides, supplemental oxygen, endothelin-receptor antagonists and/or phosphodiesterase inhibitors. Endothelin receptor antagonists and phosphodiesterase inhibitors must have been used at a stable dose for more than 12 weeks before screening.
2.Subjects with idiopathic PAH, familial pulmonary arterial hypertension and PAH associated with collagen vascular disease, corrected congenital vitium (congenital systemic to pulmonary shunts surgically repaired at least five years before) or anorexigen use.
3.Diagnosis of PAH established according to the standard criteria:
a.Resting mean pulmonary arterial pressure > 25 mmHg.
b.PVR > 240 dynes s/cm5.
c.Pulmonary capillary wedge pressure or left ventricular end diastolic pressure < 15 mmHg.
4.PVR > 400 dynes s/cm5.
5.Two 6MWTs between 150 and 500 m (inclusive) with the variation in 6MWT within ± 15% between the two tests despite other treatments for PAH.
–Two 6MWT values are needed. Only one 6MWT should be performed at screening for confirmation of eligibility if 6MWT has been previously conducted within six weeks of the screening visit unless the subject was taking another investigational drug or participating in a specific training and exercise programme at the time of the previous test.
6. Subjects who are willing and able to refrain from sunbathing, prolonged sun exposure and artificial sunlight exposure such as solarium use or UVA/UVB treatment, and to limit skin and eye exposure to sunlight using appropriate precautions (protective clothing, sunscreen and sunglasses) from the first dose until 14 days after study drug discontinuation.
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

Subjects will not be entered in the study for any of the following reasons:
1.Subjects with clinically unstable right heart failure within the last three months (NYHA Class IV).
2.Subjects who have received or have been scheduled to receive long-term treatment with epoprostenol within three months before screening.
3.Hypotensive subjects (systemic systolic blood pressure < 85 mmHg).
4.Subjects with PAH associated with portal hypertension, Human Immunodeficiency Virus infection or unrepaired congenital systemic to pulmonary shunts.
5.Subjects with ventilation-perfusion lung scan or pulmonary angiography indicative of thromboembolic disease.
6.Subjects with significant obstructive (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] < 70% predicted) or restrictive (total lung capacity < 70% predicted) lung disease.
7.In collagen vascular diseases, subjects with significant interstitial disease (FVC < 70%).
8.Subjects with evidence of left sided heart disease.
9.Subjects with moderate or severe hepatic impairment (Child-Pugh B and C).
10.Subjects with clinically significant chronic renal insufficiency (estimated creatinine clearance < 30 mL/minute, or serum creatinine > 2.5 mg/dL).
11.Subjects who are receiving or have been receiving any investigational drugs within 30 days before screening.
12.Subjects with musculoskeletal disorder limiting ambulation.
13.Females who are breast-feeding, pregnant or plan to become pregnant during the study and females who are not using a highly effective method of birth control (failure rate less than 1% per year) such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomised partner.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified