Clinical trial NCT03422328: A Clinical Study to Investigate the Long-term Safety of the Drug Macitentan in Patients With Pulmonary Hypertension Who Were Previously Treated With Macitentan in Clinical Studies.
Official title: mUlticenter, Single-arM, Open-laBel, Long-teRm Safety Study With macitEntan in Patients With puLmonary Arterial Hypertension previousLy Treated With mAcitentan in Clinical Studies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Chronic Thromboembolic Pulmonary Hypertension
Keywords: macitentan
long-term safety
open-label
single-arm
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2018-02-05
Enrollment: 151
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study is designed as an open-label, single-arm, multicenter trial in which all participants roll over from a "parent study" in order to continue their dose of macitentan 10 mg once every day as already received in the "parent study".
Primary purpose: TREATMENT

Brief summary: The aim of the trial is to study the long-term safety of macitentan and to provide continued treatment with macitentan to patients with pulmonary arterial hypertension (PAH) and Chronic thromboembolic pulmonary hypertension (CTEPH) who were previously treated with macitentan in clinical studies.

Detailed description: The purpose of this study is to provide continued treatment with macitentan to subjects with PAH or CTEPH who participated in "parent studies" and to continue to accrue long-term safety data. The design of this study is widely used in clinical programs to give participants in a clinical study access to an effective study treatment beyond completion of the parent study. This is considered the best option to collect long-term safety and tolerability information of macitentan 10 mg and survival status of participants with PAH and CTEPH. "Parent study/studies" refer to a number of clinical studies with macitentan that are conducted in different clinical classification of PAH and CTEPH (NCT00667823, NCT02112487, NCT02310672, NCT02968901, NCT02558231, NCT02382016, NCT02060721) and may be completed before the participants have access to commercial macitentan in their country of residence. The "parent studies" are fully or partially running in countries where no access to commercial macitentan is expected in the near future.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent to take part in the study before any study mandated procedure.
2. Participants from one of the parent studies and: a) the sponsor has decided to terminate the parent study in that country and b) the participant has completed the end of treatment (EOT) Visit of the parent study
3. Women of childbearing potential are able to take part in the study if the following applies: a) Urine pregnancy test is negative at Enrollment; b) Agreement to perform monthly urine or serum pregnancy tests during the study and up to at least 30 days after the study treatment discontinuation; and c) Agreement to adhere to the planned contraception scheme from Enrollment up to at least 30 days after study treatment discontinuation

Exclusion Criteria:

1. Hemoglobin less than 80 gram per liter (g/L)
2. Serum Aspartate aminotransferase (AST) and/or alanine aminotransferases (ALT) more than three times the upper limit of normal range
3. Known and documented history of severe hepatic impairment that is Child-Pugh Class C.
4. Pregnant, planning to become pregnant, or breastfeeding
5. Known hypersensitivity to macitentan, its excipients, or drugs of the same class
6. Planned or current treatment with another investigational treatment up to 3 months prior to Enrollment
7. Any known factor or disease that may interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease
8. Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir)

Primary outcomes:
measure: Incident Rate of Treatment-emergent Adverse Event
timeFrame: From Day 1 to End of study (EoS) visit (an average of 3 years)
measure: Incident rate of treatment-emergent adverse events (AEs) leading to premature discontinuation of study treatment
timeFrame: From Day 1 to EoS visit (an average of 3 years)
measure: Incident rate of treatment-emergent serious adverse events (SAEs)
timeFrame: From Day 1 to EoS visit (an average of 3 years)
measure: Number of pregnancies with maternal exposure to macitentan
timeFrame: From Day 1 to EoS visit (an average of 3 years)
Secondary outcomes:
Other outcomes:
measure: Change of WHO functional class to each scheduled time point
timeFrame: From Day 1 to EoT visit (an average of 3 years)
measure: Assessment of survival status at End-of-Study (EoS)
timeFrame: From Day 1 to EoS visit (an average of 3 years)
Locations:
city: Minsk
country: Belarus
facility: The Republican Scientific-Practical Center ''Cardiology''
city: Leuven
country: Belgium
facility: UZ Leuven
city: Besancon
country: France
facility: CHRU Besancon Hopital Jean Minjoz
city: Bordeaux (Pessac)
country: France
facility: CHU de Bordeaux - Hospital Haut-Leveque
city: Brest Cedex 2
country: France
facility: CHU de la Cavale Blanche
city: Bron Cedex
country: France
facility: GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel
city: Caen Cedex
country: France
facility: Hôpital Côte de Nacre
city: Dijon Cedex
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: Le Kremlin Bicetre cedex
country: France
facility: Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud
city: Lille Cedex
country: France
facility: Hôpital Cardiologique - Chru Lille
city: Limoges Cedex
country: France
facility: CHU de Limoges
city: Marseille cedex 5
country: France
facility: CHU de la Timone
city: Montpellier
country: France
facility: CHU de Montpellier - Arnaud de Villeneuve
city: Nantes Cedex 1
country: France
facility: CHU Nantes - Hopital Nord Laënnec
city: Nice
country: France
facility: Centre Hospitalier Universitaire - de Nice - Hopital Pasteur
city: Paris Cedex 15
country: France
facility: Hopital Europeen Georges Pompidou
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Rouen
country: France
facility: CHU Rouen Hopital Charles Nicolle
city: St Priest en Jarez Cedex
country: France
facility: CHU Saint Etienne Hopital Nord
city: Strasbourg
country: France
facility: Nouvel Hopital Civil
city: Toulouse Cedex 9
country: France
facility: Hopital Larrey CHU de Toulouse
city: Vandoeuvre les Nancy Cedex
country: France
facility: CHU de Nancy - Hopital de Brabois
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny Oddzial Kardiologiczny
city: Kemerovo
country: Russian Federation
facility: Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
city: Moscow
country: Russian Federation
facility: National Medical Research Center of Cardiology of MoH of Russian Federation
city: Novosibirsk
country: Russian Federation
facility: Federal State Budgetary Institution Of Ministry Of Health Of Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: Federal North-West Medical Research Centre
city: Tomsk
country: Russian Federation
facility: Federal State Budget Scientific Institution
city: Capa_Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty
city: Dnipro
country: Ukraine
facility: CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital
Study officials:
affiliation: Actelion
name: Marek Sochor
role: STUDY_DIRECTOR
References: