Study of ACT-293987 (NS-304) in Pulmonary Arterial Hypertension (PAH)

This study has been completed.
Sponsor:
Information provided by:
Actelion
ClinicalTrials.gov Identifier:
NCT00993408
First received: October 9, 2009
Last updated: NA
Last verified: October 2009
History: No changes posted
  Purpose

This is a multi-centre, multinational, open-label, single-dose acute hemodynamic study followed by randomized, double-blind, parallel-group, placebo controlled study. Eligible subjects will undergo an open-label, single-dose acute hemodynamic study with ACT-293987(NS-304) and 21 weeks of double-blind treatment during which subjects will receive either ACT-293987 (NS-304) or placebo b.i.d. Subjects who have completed the double-blind study can enter the open extension study (separate protocol) and receive administration of ACT-293987 (NS-304) if the subject wishes and the Investigator considers it appropriate.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Device: ACT-293987 (NS-304)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Official Title: A Multi-centre, Multinational, Open-label, Single-dose Acute Hemodynamic Study Followed by 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

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Assessment of hemodynamic parameters after single oral dose of ACT-293987. [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]
  • Proof-of-concept assessment of the efficacy of ACT-293987 in subjects with PAH by measuring the change from baseline in the PVR at Week 17 compared to placebo. [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of a single oral dose of ACT-293987. [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]
  • Assessments of preliminary efficacy of ACT-293987 regarding 6 minute walk test (6MWT), proportion of subjects with aggravation of PAH, hemodynamic parameters other than PVR [ Time Frame: 17 weeks ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: April 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACT-293987 (NS-304) and matching placebo

Subjects will be randomized to the study following screening.

Each subject will then undergo an acute hemodynamic study with right heart catheterization after a single oral administration of ACT-293987 (NS-304)on Day 0. The objectives are to collect data about the drug effect on the right heart hemodynamic parameters (PVR, calculated SVR and PVR/SVR) measured by right heart catheterization after single oral dose administration of NS-304 and to assess the safety and tolerability of a single oral dose of NS-304.

Device: ACT-293987 (NS-304)

Detailed Description:

This is a multi-centre, multinational, open-label, single-dose acute hemodynamic study followed by a randomized, double-blind, parallel-group, placebo controlled study. Eligible subjects will undergo screening followed by randomized allocation to treatment group for the double-blind study, followed in turn by immediate enrollment in an open-label, single-dose acute hemodynamic study with ACT-293987 (NS-304) and 21 weeks of double-blind treatment during which subjects will receive either ACT-293987 (NS-304)or placebo twice daily (b.i.d.). Subjects who have completed the double-blind study can enter the open extension study and receive administration of ACT-293987 (NS-304) (separate protocol)if the subject wishes and the investigator considers it appropriate.

Unblinding will occur on a subject-by-subject basis when the Week 17 data for the subject have been fixed.

Approximately 44 subjects are to be randomized in a ratio of 3:1 to the two treatment groups, ACT-293987 (NS-304) and placebo (33 subjects to ACT-293987 (NS-304) and 11 subjects to placebo).

Subjects will be randomized to the study following screening.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    1. Resting mean pulmonary arterial pressure > 25 mmHg.
    2. PVR > 240 dynes s/cm5.
    3. 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 able and willing to refrain from sunbathing, prolonged sun exposure, and solarium use, 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.

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% predicted).
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993408

Locations
Austria
Medizinische Universitat Wien, Universitatsklinik fur Innere Medizin II, Kardiologie
Vienna, Austria, 1090
Belgium
Gasthuisberg University Hospital, Pneumology
Leuven, Belgium, 3000
France
Hopital Antoine Beclere, Pneumologie
Paris, France
Germany
Department of Respiratory Medicine, Hannover Medical School
Hannover, Germany, 30625
Hungary
Semmelweis University, Clinic of Pulmonology
Budapest, Hungary, H-1125
Italy
Hospital Sant'Orsola Malpighi, Cardiology's Department
Bologna, Italy, 40138
Poland
Instytut Gruzilcy i Chorob Pluc, Klinika Chorob Wewnetrznych Klatki Piersiowej
Warsaw, Poland, 01-138
United Kingdom
Hammersmith Hospital
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Actelion
  More Information

No publications provided by Actelion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00993408     History of Changes
Other Study ID Numbers: NS-304/-02
Study First Received: October 9, 2009
Last Updated: October 9, 2009
Health Authority: France: Institutional Ethical Committee

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014