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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00660179




Registration number
NCT00660179
Ethics application status
Date submitted
14/04/2008
Date registered
17/04/2008
Date last updated
28/09/2015

Titles & IDs
Public title
Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Scientific title
A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Phase III Study to Assess the Effects of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Secondary ID [1] 0 0
AC-055-302
Universal Trial Number (UTN)
Trial acronym
SERAPHIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - macitentan (ACT-064992)
Treatment: Drugs - macitentan (ACT-064992)
Treatment: Drugs - placebo

Experimental: 1 - Macitentan (ACT-064992) tablet, 3 mg, once daily

Experimental: 2 - Macitentan (ACT-064992) tablet, 10 mg, once daily

Placebo comparator: 3 - Matching placebo, once daily


Treatment: Drugs: macitentan (ACT-064992)
Tablet, 3 mg dosage, once daily

Treatment: Drugs: macitentan (ACT-064992)
Tablet, 10 mg dosage, once daily

Treatment: Drugs: placebo
Matching placebo, once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to end of treatment (data presented up to month 36)
Secondary outcome [1] 0 0
Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Timepoint [1] 0 0
Up to end of treatment (data presented up to month 36)
Secondary outcome [2] 0 0
Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Timepoint [2] 0 0
Up to end of treatment (data presented up to month 36)
Secondary outcome [3] 0 0
Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event)
Timepoint [3] 0 0
Up to end of study (data presented up to month 36)
Secondary outcome [4] 0 0
Change From Baseline to Month 6 in 6-minute Walk Distance
Timepoint [4] 0 0
Baseline to month 6
Secondary outcome [5] 0 0
Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6
Timepoint [5] 0 0
Baseline to month 6
Secondary outcome [6] 0 0
Pulmonary Vascular Resistance at Baseline and Month 6
Timepoint [6] 0 0
Baseline to month 6
Secondary outcome [7] 0 0
Cardiac Index at Baseline and Month 6
Timepoint [7] 0 0
Baseline to month 6

Eligibility
Key inclusion criteria
1. Signed informed consent prior to initiation of any study mandated procedure.
2. Patients with symptomatic pulmonary arterial hypertension (PAH) in modified World Health Organization (WHO) functional class II to IV.
3. 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.
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/cm^5.
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).
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 mammalian target of rapamycin (mTOR) inhibitors).
21. Treatment with cytochrome P3A (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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Darlinghurst, NSW
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne, VIC
Recruitment hospital [3] 0 0
Royal Brisbane Hospital - Sunshine Coast
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, NSW
Recruitment postcode(s) [2] 0 0
3181 - Melbourne, VIC
Recruitment postcode(s) [3] 0 0
4558 - Sunshine Coast
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Parow
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Malaga
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Chiang Mai
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Khon Kaen
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Turkey
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Istanbul
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Ukraine
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Dnepropetrovsk
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Ukraine
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Lviv
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Loic Perchenet, PhD
Address 0 0
Actelion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Pulido T, Adzerikho I, Channick RN, Delcroix M, Ga... [More Details]