Phase 3
Completed N=742
Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Source: ClinicalTrials.gov NCT00660179 ↗Enrolled (actual)
742
Serious AEs
50.7%
Results posted
May 2014
Primary outcomePrimary: Time to First Confirmed Morbidity or Mortality Event up to the End of Treatment (Kaplan-Meier Estimate of Patients Without a Morbidity or Mortality Event) — 80.1; 89.3; 92.7; 71.4 percentage of participants-Kaplan Meier — p=0.0108
Summary
The AC-055-302/SERAPHIN study will be an event-driven Phase III study, comparing two different doses of macitentan (ACT-064992) (3 and 10 mg) vs placebo in patients with symptomatic PAH. The main study objective is to demonstrate that macitentan (ACT-064992) prolongs time to the first morbidity or mortality event, and to evaluate the benefit/risk profile of macitentan (ACT-064992) in the treatment of patients with symptomatic PAH.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to First Confirmed Morbidity or Mortality Event up to the End of Treatment (Kaplan-Meier Estimate of Patients Without a Morbidity or Mortality Event) |
80.1; 89.3; 92.7; 71.4; 81.6; 85.5 | 0.0108 sig |
| SECONDARY Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event) |
84.8; 90.8; 94.6; 76.7; 84.9; 89.8 | 0.0146 sig |
| SECONDARY Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event) |
95.2; 97.1; 97.4; 93.6; 95.6; 96.4 | 0.9249 |
| SECONDARY Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event) |
94.7; 96.4; 96.3; 91.4; 93.9; 95.0 | 0.8312 |
| SECONDARY Change From Baseline to Month 6 in 6-minute Walk Distance |
352; 364; 363; -9.4; 7.4; 12.5 | — |
| SECONDARY Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6 |
32; 49; 54 | — |
| SECONDARY Pulmonary Vascular Resistance at Baseline and Month 6 |
886; 945; 907; 1042; 736; 680 | — |
| SECONDARY Cardiac Index at Baseline and Month 6 |
2.54; 2.34; 2.63; 2.21; 2.69; 2.93 | — |
Eligibility Criteria
Inclusion Criteria
- Signed informed consent prior to initiation of any study mandated procedure.
- Patients with symptomatic pulmonary arterial hypertension (PAH) in modified World Health Organization (WHO) functional class II to IV.
- Patients with the following types of pulmonary arterial hypertension (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;
- Human immunodeficiency virus (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) = 320 dyn×sec/cm^5.
- 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) 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 mammalian target of rapamycin (mTOR) inhibitors).
- Treatment with cytochrome P3A (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.
Data sourced from ClinicalTrials.gov (NCT00660179). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.