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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. (UMBRELLA)

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03422328
Recruitment Status : Enrolling by invitation
First Posted : February 5, 2018
Last Update Posted : November 9, 2022
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Chronic Thromboembolic Pulmonary Hypertension Drug: macitentan Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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".
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 5, 2018
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022

Arm Intervention/treatment
Experimental: Open-label macitentan 10 mg
10 mg macitentan film coated tablet, administered orally once daily
Drug: macitentan
macitentan 10 mg, film-coated tablet, oral use
Other Names:
  • ACT-064992
  • JNJ-67896062

Primary Outcome Measures :
  1. Incident Rate of Treatment-emergent Adverse Event [ Time Frame: From 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.

  2. Incident rate of treatment-emergent adverse events (AEs) leading to premature discontinuation of study treatment [ Time Frame: From 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.

  3. Incident rate of treatment-emergent serious adverse events (SAEs) [ Time Frame: 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.

  4. Number of pregnancies with maternal exposure to macitentan [ Time Frame: From Day 1 to EoS visit (an average of 3 years) ]
    Pregnancies with maternal exposure to macitentan will be recorded.

Other Outcome Measures:
  1. Change of WHO functional class to each scheduled time point [ Time Frame: From Day 1 to EoT visit (an average of 3 years) ]
    The proportion of patients who worsened, remain unchanged or improved from baseline to each scheduled time-point in WHO function will be calculated, where baseline is the initial baseline from the "parent study" (or the double-blind core study preceding the "parent study").

  2. Assessment of survival status at End-of-Study (EoS) [ Time Frame: From Day 1 to EoS visit (an average of 3 years) ]
    Time to death of all causes up to EoS from the date of randomization or enrollment in the "parent study" (or the double-blind core study preceding the "parent study") will be estimated.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03422328

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Sponsors and Collaborators
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Study Director: Marek Sochor Actelion
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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT03422328    
Other Study ID Numbers: AC-055-314
2017-003934-10 ( EudraCT Number )
First Posted: February 5, 2018    Key Record Dates
Last Update Posted: November 9, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Actelion:
long-term safety
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists