Study of ACT-064992 on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension

Tracking Information

Start Date  ICMJEJune 2008
Estimated Primary Completion DateFebruary 2012   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: April 16, 2008)
To demonstrate that either dose of ACT-064992 prolongs the time to first morbidity or mortality event in patients with symptomatic pulmonary arterial hypertension. [ Time Frame: End of Study ] [ Designated as safety issue: No ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00660179 on Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: April 16, 2008)
To evaluate the safety and tolerability of ACT-064992 in patients with symptomatic pulmonary arterial hypertension [ Time Frame: End of Study ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEStudy of ACT-064992 on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Official Title  ICMJEA Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Phase III Study to Assess the Effects of ACT-064992 on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Brief Summary

The AC-055-302/SERAPHIN study will be an event-driven Phase III study, comparing two different doses of ACT-064992 (3 and 10 mg) vs placebo in patients with symptomatic PAH. The main study objective is to demonstrate that ACT-064992 prolongs time to the first morbidity or mortality event, and to evaluate the benefit/risk profile of ACT-064992 in the treatment of patients with symptomatic PAH.

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Condition  ICMJEPulmonary Arterial Hypertension
Intervention  ICMJE
  • Drug: ACT-064992
    Tablet, 3 mg dosage, once daily
  • Drug: ACT-064992
    Tablet, 10 mg dosage, once daily
  • Drug: Placebo
    Matching ACT-064992 placebo, once daily
Study Arms / Comparison Groups
  • 1: Experimental
    ACT-064992 tablet, 3 mg, once daily
    Intervention: Drug: ACT-064992
  • 2: Experimental
    ACT-064992 tablet, 10 mg, once daily
    Intervention: Drug: ACT-064992
  • 3: Placebo Comparator
    Matching ACT-064992 placebo, once daily
    Intervention: Drug: Placebo

Recruitment Information

Estimated Enrollment  ICMJE699
Estimated Completion DateFebruary 2012
Estimated Primary Completion DateFebruary 2012   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed informed consent prior to initiation of any study mandated procedure.
  2. Patients with symptomatic pulmonary arterial hypertension (PAH) in modified WHO functional class II to IV.
  3. Patients with the following types of PAH belonging to groups 1.1 to 1.3 of the Venice classification:

    • Idiopathic (IPAH);
    • Familial (FPAH); or
    • Related to:

      • Collagen vascular disease;
      • Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair;
      • HIV infection; or
      • Drugs and toxins.
  4. PAH diagnosis confirmed by hemodynamic evaluation performed prior to randomization and showing all of the following:

    • Mean pulmonary artery pressure (mPAP) > 25 mmHg at rest;
    • Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) < 15 mmHg; and
    • Pulmonary vascular resistance (PVR) at rest >= 320 dyn×sec/cm5.
  5. 6-minute walk distance (6MWD) >= 50 m.
  6. Men or women > 12 years of age (women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception).

Exclusion Criteria:

  1. PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher''s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy.
  2. PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected.
  3. PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
  4. Persistent pulmonary hypertension of the newborn.
  5. Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification.
  6. Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 65% of predicted value after bronchodilator administration.
  7. Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value.
  8. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
  9. Estimated creatinine clearance < 30 mL/min
  10. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal.
  11. Hemoglobin < 75% of the lower limit of the normal range.
  12. Systolic blood pressure < 100 mmHg.
  13. Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
  14. Pregnant or breast-feeding.
  15. Known concomitant life-threatening disease with a life expectancy < 12 months.
  16. Body weight < 40 kg.
  17. Any condition that prevents compliance with the protocol or adherence to therapy.
  18. Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise.
  19. Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
  20. Systemic treatment within 4 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mTOR inhibitors).
  21. Treatment with CYP3A inducers within 4 weeks prior to randomization
  22. Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
  23. Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
Ages12 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE 
Location Countries  ICMJEUnited States,   Argentina,   Australia,   Austria,   Belarus,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   Colombia,   Croatia,   Denmark,   Finland,   France,   Germany,   Hong Kong,   Hungary,   India,   Israel,   Italy,   Malaysia,   Mexico,   Netherlands,   Norway,   Peru,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom

Administrative Information

Responsible PartySebastien Roux, MD, Actelion
Study ID Numbers  ICMJEAC-055-302
Study Sponsor  ICMJEActelion
Collaborators  ICMJE 
Investigators  ICMJE
Study Chair:Loic Perchenet, PhDActelion
Information Provided ByActelion