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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00993408
Recruitment Status : Completed
First Posted : October 12, 2009
Last Update Posted : October 12, 2009
Sponsor:
Information provided by:
Actelion

Tracking Information
First Submitted Date  ICMJE October 9, 2009
First Posted Date  ICMJE October 12, 2009
Last Update Posted Date October 12, 2009
Study Start Date  ICMJE April 2008
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2009)
  • Assessment of hemodynamic parameters after single oral dose of ACT-293987. [ Time Frame: 17 weeks ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2009)
  • Safety and tolerability of a single oral dose of ACT-293987. [ Time Frame: 17 weeks ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ACT-293987 (NS-304) in Pulmonary Arterial Hypertension (PAH)
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE Device: ACT-293987 (NS-304)
Study Arms  ICMJE 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.

Intervention: Device: ACT-293987 (NS-304)
Publications * Simonneau G, Torbicki A, Hoeper MM, Delcroix M, Karlócai K, Galiè N, Degano B, Bonderman D, Kurzyna M, Efficace M, Giorgino R, Lang IM. Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012 Oct;40(4):874-80. Epub 2012 Feb 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 9, 2009)
43
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2009
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   France,   Germany,   Hungary,   Italy,   Poland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00993408
Other Study ID Numbers  ICMJE NS-304/-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Actelion
Verification Date October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP