Study of ACT-064992 on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Tracking InformationStart Date ICMJE | June 2008 |
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Estimated Primary Completion Date | February 2012 (final data collection date for primary outcome measure) |
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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 ] |
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Original Primary Outcome Measures ICMJE | Same as current |
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Change History | Complete list of historical versions of study NCT00660179 on ClinicalTrials.gov Archive Site |
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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 ] |
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Original Secondary Outcome Measures ICMJE | Same as current |
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Descriptive InformationBrief Title ICMJE | Study of ACT-064992 on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension |
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Official Title ICMJE | A 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 |
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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. |
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Detailed Description | |
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Study Phase | Phase III |
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Study Type ICMJE | Interventional |
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Study Design ICMJE | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
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Condition ICMJE | Pulmonary Arterial Hypertension |
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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
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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
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Recruitment InformationEstimated Enrollment ICMJE | 699 |
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Estimated Completion Date | February 2012 |
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Estimated Primary Completion Date | February 2012 (final data collection date for primary outcome measure) |
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Eligibility Criteria ICMJE | Inclusion Criteria: - Signed informed consent prior to initiation of any study mandated procedure.
- Patients with symptomatic pulmonary arterial hypertension (PAH) in modified WHO functional class II to IV.
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.
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.
- 6-minute walk distance (6MWD) >= 50 m.
- 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: - PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher''s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy.
- PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected.
- PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
- Persistent pulmonary hypertension of the newborn.
- Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification.
- 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.
- Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value.
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
- Estimated creatinine clearance < 30 mL/min
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal.
- Hemoglobin < 75% of the lower limit of the normal range.
- Systolic blood pressure < 100 mmHg.
- Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
- Pregnant or breast-feeding.
- Known concomitant life-threatening disease with a life expectancy < 12 months.
- Body weight < 40 kg.
- Any condition that prevents compliance with the protocol or adherence to therapy.
- Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise.
- Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
- Systemic treatment within 4 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mTOR inhibitors).
- Treatment with CYP3A inducers within 4 weeks prior to randomization
- Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
- Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
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Gender | Both |
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Ages | 12 Years and older |
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Accepts Healthy Volunteers | No |
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Contacts ICMJE | |
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Location Countries ICMJE | United 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 |
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Administrative InformationNCT ID ICMJE | NCT00660179 |
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Responsible Party | Sebastien Roux, MD, Actelion |
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Study ID Numbers ICMJE | AC-055-302 |
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Study Sponsor ICMJE | Actelion |
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Collaborators ICMJE | |
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Investigators ICMJE | Study Chair: | Loic Perchenet, PhD | Actelion | |
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Information Provided By | Actelion |
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