Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00667823




Registration number
NCT00667823
Ethics application status
Date submitted
24/04/2008
Date registered
28/04/2008
Date last updated
10/02/2022

Titles & IDs
Public title
Clinical Study to Assess the Long-term Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension
Scientific title
Long-term Single-arm Open-label Extension Study of the SERAPHIN Study, to Assess the Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension
Secondary ID [1] 0 0
AC-055-303
Universal Trial Number (UTN)
Trial acronym
SERAPHIN OL
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

Experimental: ACT-064992 - ACT-064992


Treatment: Drugs: Macitentan
Tablet, oral administration, 10 mg dose once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) up to 28 Days After Study Treatment Discontinuation
Timepoint [1] 0 0
Up to 28 days after study treatment discontinuation (Up to 12 years)
Primary outcome [2] 0 0
Number of Participants With Death up to 28 Days After Study Treatment Discontinuation
Timepoint [2] 0 0
Up to 28 days after study treatment discontinuation (Up to 12 years)
Primary outcome [3] 0 0
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) up to 28 Days After Study Treatment Discontinuation
Timepoint [3] 0 0
Up to 28 days after study treatment discontinuation (Up to 12 years)
Primary outcome [4] 0 0
Number of Participants With AEs Leading to Permanent Discontinuation of Study Treatment
Timepoint [4] 0 0
Up to 28 days after study treatment discontinuation (Up to12 years)
Primary outcome [5] 0 0
Number of Participants With Treatment Emergent Abnormal Liver Tests up to 28 Days After Study Treatment Discontinuation
Timepoint [5] 0 0
Up to 28 days after study treatment discontinuation (Up to12 years)
Primary outcome [6] 0 0
Number of Participants With Treatment Emergent Hemoglobin Abnormality up to 28 Days After Study Treatment Discontinuation
Timepoint [6] 0 0
Up to 28 days after treatment discontinuation (Up to 12 years)

Eligibility
Key inclusion criteria
* Signed informed consent prior to initiation of any study-mandated procedure.
* Patients with pulmonary arterial hypertension and having completed the event-driven study, AC 055 302/SERAPHIN, or Patients who have experienced a clinical worsening of PAH in AC 055 302/SERAPHIN and for whom a written approval to roll over into this study has been obtained from the Sponsor.
* Women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception during study treatment and for at least 28 days after study treatment termination.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any major violation of protocol AC 055 302/SERAPHIN.
* Pregnancy or breast-feeding.
* AST and/or ALT > 3 times the upper limit of the normal range.
* Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
* Known hypersensitivity to ACT 064992 or any of the excipients.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
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
17/10/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/12/2020
Sample size
Target
Accrual to date
Final
550
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Royal Brisbane Hospital - Sunshine Coast
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
4558 - Sunshine Coast
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maine
Country [13] 0 0
United States of America
State/province [13] 0 0
Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Massachusetts
Country [15] 0 0
United States of America
State/province [15] 0 0
Michigan
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
Nebraska
Country [18] 0 0
United States of America
State/province [18] 0 0
New Jersey
Country [19] 0 0
United States of America
State/province [19] 0 0
New York
Country [20] 0 0
United States of America
State/province [20] 0 0
North Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Utah
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Argentina
State/province [28] 0 0
Ciudad Autonoma
Country [29] 0 0
Argentina
State/province [29] 0 0
Buenos Aires
Country [30] 0 0
Argentina
State/province [30] 0 0
Cordoba
Country [31] 0 0
Argentina
State/province [31] 0 0
Corrientes
Country [32] 0 0
Argentina
State/province [32] 0 0
Santa Fe
Country [33] 0 0
Austria
State/province [33] 0 0
Vienna
Country [34] 0 0
Belarus
State/province [34] 0 0
Minsk
Country [35] 0 0
Belarus
State/province [35] 0 0
Vitebsk
Country [36] 0 0
Belgium
State/province [36] 0 0
Leuven
Country [37] 0 0
Bulgaria
State/province [37] 0 0
BG
Country [38] 0 0
Canada
State/province [38] 0 0
Alberta
Country [39] 0 0
Canada
State/province [39] 0 0
Ontario
Country [40] 0 0
Canada
State/province [40] 0 0
Quebec
Country [41] 0 0
Chile
State/province [41] 0 0
Santiago de Chile
Country [42] 0 0
Chile
State/province [42] 0 0
Santiago
Country [43] 0 0
China
State/province [43] 0 0
Beijing
Country [44] 0 0
China
State/province [44] 0 0
Guangzhou
Country [45] 0 0
China
State/province [45] 0 0
Nanjing
Country [46] 0 0
China
State/province [46] 0 0
Shanghai
Country [47] 0 0
Colombia
State/province [47] 0 0
Santander
Country [48] 0 0
Colombia
State/province [48] 0 0
Bogota
Country [49] 0 0
Croatia
State/province [49] 0 0
Rijeka
Country [50] 0 0
Finland
State/province [50] 0 0
Helsinki
Country [51] 0 0
France
State/province [51] 0 0
Le Kremlin-Bicêtre cedex
Country [52] 0 0
France
State/province [52] 0 0
Montpellier
Country [53] 0 0
France
State/province [53] 0 0
Pessac
Country [54] 0 0
Germany
State/province [54] 0 0
Berlin
Country [55] 0 0
Germany
State/province [55] 0 0
Dresden
Country [56] 0 0
Germany
State/province [56] 0 0
Essen
Country [57] 0 0
Germany
State/province [57] 0 0
Giessen
Country [58] 0 0
Germany
State/province [58] 0 0
Greifswald
Country [59] 0 0
Germany
State/province [59] 0 0
Hamburg
Country [60] 0 0
Germany
State/province [60] 0 0
Hannover
Country [61] 0 0
Germany
State/province [61] 0 0
Heidelberg
Country [62] 0 0
Germany
State/province [62] 0 0
Homburg/Saar
Country [63] 0 0
Germany
State/province [63] 0 0
Koln
Country [64] 0 0
Germany
State/province [64] 0 0
Leipzig
Country [65] 0 0
Germany
State/province [65] 0 0
Munich
Country [66] 0 0
Germany
State/province [66] 0 0
Regensburg
Country [67] 0 0
Hong Kong
State/province [67] 0 0
Hong Kong
Country [68] 0 0
Hungary
State/province [68] 0 0
Budapest
Country [69] 0 0
Hungary
State/province [69] 0 0
Pecs
Country [70] 0 0
Hungary
State/province [70] 0 0
Szeged
Country [71] 0 0
India
State/province [71] 0 0
Ahmedabad
Country [72] 0 0
India
State/province [72] 0 0
Hyderabad
Country [73] 0 0
India
State/province [73] 0 0
Mumbai
Country [74] 0 0
India
State/province [74] 0 0
New Delhi
Country [75] 0 0
India
State/province [75] 0 0
Pune
Country [76] 0 0
Israel
State/province [76] 0 0
Haifa
Country [77] 0 0
Israel
State/province [77] 0 0
Petach - Tikvah
Country [78] 0 0
Israel
State/province [78] 0 0
Rehovot
Country [79] 0 0
Israel
State/province [79] 0 0
Tel Hashomer
Country [80] 0 0
Israel
State/province [80] 0 0
Tel-Aviv
Country [81] 0 0
Italy
State/province [81] 0 0
Pavia
Country [82] 0 0
Italy
State/province [82] 0 0
Roma
Country [83] 0 0
Malaysia
State/province [83] 0 0
Kuala Lumpur
Country [84] 0 0
Mexico
State/province [84] 0 0
Mexico City
Country [85] 0 0
Mexico
State/province [85] 0 0
Monterrey
Country [86] 0 0
Netherlands
State/province [86] 0 0
Amsterdam
Country [87] 0 0
Netherlands
State/province [87] 0 0
Nieuwegein
Country [88] 0 0
Peru
State/province [88] 0 0
Callao
Country [89] 0 0
Peru
State/province [89] 0 0
Lima
Country [90] 0 0
Poland
State/province [90] 0 0
Krakow
Country [91] 0 0
Poland
State/province [91] 0 0
Otwock
Country [92] 0 0
Poland
State/province [92] 0 0
Zabrze
Country [93] 0 0
Romania
State/province [93] 0 0
Bucharest
Country [94] 0 0
Romania
State/province [94] 0 0
Bucuresti
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Ekaterinburg
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Kemerovo
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Moscow
Country [98] 0 0
Russian Federation
State/province [98] 0 0
St Petersburg
Country [99] 0 0
Russian Federation
State/province [99] 0 0
St. Petersburg
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Tomsk
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Yaroslavl
Country [102] 0 0
Serbia
State/province [102] 0 0
Belgrade
Country [103] 0 0
Singapore
State/province [103] 0 0
Singapore
Country [104] 0 0
Slovakia
State/province [104] 0 0
Bratislava
Country [105] 0 0
South Africa
State/province [105] 0 0
Cape Town
Country [106] 0 0
South Africa
State/province [106] 0 0
Johannesburg
Country [107] 0 0
South Africa
State/province [107] 0 0
Somerset West
Country [108] 0 0
Sweden
State/province [108] 0 0
Lund
Country [109] 0 0
Sweden
State/province [109] 0 0
Uppsala
Country [110] 0 0
Taiwan
State/province [110] 0 0
Taichung
Country [111] 0 0
Taiwan
State/province [111] 0 0
Taipei
Country [112] 0 0
Thailand
State/province [112] 0 0
Bangkok
Country [113] 0 0
Thailand
State/province [113] 0 0
Chiang Mai
Country [114] 0 0
Thailand
State/province [114] 0 0
Khon Kaen
Country [115] 0 0
Ukraine
State/province [115] 0 0
Dnepropetrovsk
Country [116] 0 0
Ukraine
State/province [116] 0 0
Lviv
Country [117] 0 0
Ukraine
State/province [117] 0 0
Odessa
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
The main objective of the AC 055 303/SERAPHIN OL study, which will follow the AC 055 302/SERAPHIN study, will be to assess the long-term safety and tolerability of ACT 064992 in patients with symptomatic PAH.
Trial website
https://clinicaltrials.gov/study/NCT00667823
Trial related presentations / publications
Souza R, Delcroix M, Galie N, Jansa P, Mehta S, Pulido T, Rubin L, Sastry BKS, Simonneau G, Sitbon O, Torbicki A, Boyanova N, Chamitava L, Stein C, Channick RN. Long-Term Safety, Tolerability and Survival in Patients with Pulmonary Arterial Hypertension Treated with Macitentan: Results from the SERAPHIN Open-Label Extension. Adv Ther. 2022 Sep;39(9):4374-4390. doi: 10.1007/s12325-022-02199-x. Epub 2022 Jul 12.
Krause A, Zisowsky J, Dingemanse J. Modeling of pharmacokinetics, efficacy, and hemodynamic effects of macitentan in patients with pulmonary arterial hypertension. Pulm Pharmacol Ther. 2018 Apr;49:140-146. doi: 10.1016/j.pupt.2018.02.005. Epub 2018 Feb 28.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00667823