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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.

Phase 3
Completed
Conditions
Pulmonary Arterial Hypertension
Chronic Thromboembolic Pulmonary Hypertension
Interventions
Registration Number
NCT03422328
Lead Sponsor
Actelion
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
151
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Open-label macitentan 10 mgmacitentan10 mg macitentan film coated tablet, administered orally once daily
Primary Outcome Measures
NameTimeMethod
Incident Rate of Treatment-emergent Adverse EventFrom Day 1 to End of study (EoS) visit (an average of 3 years)

An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A treatment-emergent AE is any AE temporally associated with the use of study treatment.

Incident rate of treatment-emergent adverse events (AEs) leading to premature discontinuation of study treatmentFrom Day 1 to EoS visit (an average of 3 years)

Any AE will be recorded that 1) is (temporally) associated with the use of study treatment whether or not considered by the investigator as related to study treatment and 2) leads to premature discontinuation of study medication.

Incident rate of treatment-emergent serious adverse events (SAEs)From Day 1 to EoS visit (an average of 3 years)

Any SAE as defined by the ICH guidelines will be recorded. Any hepatic AE that leads to discontinuation of study treatment will be defined as SAE.

Number of pregnancies with maternal exposure to macitentanFrom Day 1 to EoS visit (an average of 3 years)

Pregnancies with maternal exposure to macitentan will be recorded.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (34)

The Republican Scientific-Practical Center ''Cardiology''

🇧🇾

Minsk, Belarus

UZ Leuven

🇧🇪

Leuven, Belgium

CHRU Besancon Hopital Jean Minjoz

🇫🇷

Besancon, France

CHU de Bordeaux - Hospital Haut-Leveque

🇫🇷

Bordeaux (Pessac), France

CHU de la Cavale Blanche

🇫🇷

Brest Cedex 2, France

GH est - Hôpital Cardiovasculaire et Pneumologie Louis Pradel

🇫🇷

Bron Cedex, France

Hôpital Côte de Nacre

🇫🇷

Caen Cedex, France

CHU Dijon

🇫🇷

Dijon Cedex, France

CHU Grenoble

🇫🇷

Grenoble, France

Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud

🇫🇷

Le Kremlin Bicetre cedex, France

Hôpital Cardiologique - Chru Lille

🇫🇷

Lille Cedex, France

CHU de Limoges

🇫🇷

Limoges Cedex, France

CHU de la Timone

🇫🇷

Marseille cedex 5, France

CHU de Montpellier - Arnaud de Villeneuve

🇫🇷

Montpellier, France

CHU Nantes - Hopital Nord Laënnec

🇫🇷

Nantes Cedex 1, France

Centre Hospitalier Universitaire - de Nice - Hopital Pasteur

🇫🇷

Nice, France

Hopital Europeen Georges Pompidou

🇫🇷

Paris Cedex 15, France

CHU de Reims

🇫🇷

Reims, France

Chu Rennes Hopital Pontchaillou

🇫🇷

Rennes, France

CHU Rouen Hopital Charles Nicolle

🇫🇷

Rouen, France

CHU Saint Etienne Hopital Nord

🇫🇷

St Priest en Jarez Cedex, France

Nouvel Hopital Civil

🇫🇷

Strasbourg, France

Hopital Larrey CHU de Toulouse

🇫🇷

Toulouse Cedex 9, France

CHU de Nancy - Hopital de Brabois

🇫🇷

Vandoeuvre les Nancy Cedex, France

Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ

🇵🇱

Lublin, Poland

Wojewodzki Szpital Specjalistyczny Oddzial Kardiologiczny

🇵🇱

Wroclaw, Poland

Cardiovascular Pathology Research Institute of Siberian Branch of RAMS

🇷🇺

Kemerovo, Russian Federation

National Medical Research Center of Cardiology of MoH of Russian Federation

🇷🇺

Moscow, Russian Federation

Federal State Budgetary Institution Of Ministry Of Health Of Russian Federation

🇷🇺

Novosibirsk, Russian Federation

Federal North-West Medical Research Centre

🇷🇺

Saint-Petersburg, Russian Federation

Federal State Budget Scientific Institution

🇷🇺

Tomsk, Russian Federation

Istanbul University Istanbul Medical Faculty

🇹🇷

Capa_Istanbul, Turkey

CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'

🇺🇦

Dnipro, Ukraine

Lviv Regional Clinical Hospital

🇺🇦

Lviv, Ukraine

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