Hypertension, Pulmonary
Conditions
Keywords
Chronic thromboembolic pulmonary hypertension (CTEPH), pulmonary arterial hypertension (PAH)
Brief summary
The purpose of the study is to enable participants with pulmonary hypertension (PH) currently treated with study intervention(s) in a clinical study (parent studies \[NCT03422328, NCT03904693,NCT04565990, NCT02932410, NCT03492177, and NCT04175600\]), to continue to benefit from the intervention after closure of the parent study in case they have no alternative means of access to the study intervention. This study will allow assessment of the long-term safety of each study intervention.
Interventions
DRUGMacitentan
Adult participants will receive oral dose of macitentan 10 milligrams (mg) tablet once daily. Children greater than or equal to (\>=) 2 year to less than (\<) 18 years will be given an oral macitentan dose tailored to their body weight, ensuring an equivalent level of systemic exposure as in adults.
DRUGSelexipag
Adult Participant will receive oral dose of selexipag tablet twice daily at the dose strength corresponding to their maintenance dose at the end of their parent study. Available strengths: 200, 400, 600, 800, 1000, 1200, 1400 and 1600 micrograms (µg). Children with body weight category of \>=50 kg will use the tablets at the required dose strength as described for adults. Children with a body weight \< 50 kg will receive tablets for pediatric use (dose strengths: 100 and 150 mcg), twice daily to enable continuation of individually maximum tolerated dose of selexipag according to their body weight category.
DRUGMacitentan/Tadalafil FDC
Participants will receive oral FDC of macitentan 10 mg and tadalafil 40 mg once daily during the course of the study as already received in the parent studies.
Sponsors
Actelion
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a prospective, open-label, extension study, with a platform-study design for long-term safety follow-up of participants using study intervention as in their respective pulmonary hypertension (PH) parent study (that is, pulmonary arterial hypertension \[PAH\] or chronic thromboembolic pulmonary hypertension \[CTEPH\]). Participants who have completed a parent study, that benefit from their study intervention maintenance and have no adequate alternative local treatment option (access to the study intervention or an equivalent approved therapy) will be enrolled in this study.
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must sign an informed consent form (ICF) (or their legally designated representative must sign) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study * Participant treated with oral macitentan or selexipag or fixed dose combination (FDC) of macitentan 10 milligrams (mg) and tadalafil 40 mg at the end of a sponsor parent study and: a) the indication of the parent study is included in the intervention-specific appendices (ISA) (pulmonary arterial hypertension \[PAH\]; b) participant has completed the parent study; c) no alternative means of access to study intervention (or equivalent approved therapy) have been identified; d) participant may continue to benefit from treatment with the study intervention; e) Participant is at least 18 years old for macitentan/tadalafil FDC, and at least 2 years old for macitentan or selexipag * A female participant of childbearing potential must: a) have a negative urine or serum pregnancy test prior to first intake of study intervention; b) agree to perform monthly urine pregnancy test up to the end of the safety follow-up period; c) If heterosexually active, agree to follow contraceptive methods until 30 days after the last intake of the study intervention. For pediatric female participants: It is the responsibility of the investigator to ensure appropriate counselling, including consultation with a specialist (if needed), to the participant and/or parent(s)/ legally designated representative (LDR)(s) on the acceptable method of contraception
Exclusion criteria
General: * Participants prematurely discontinued from the study intervention in their parent study * Female participant being pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study * Planned or current treatment with another investigational treatment Macitentan-specific: * Known allergies, hypersensitivity, or intolerance to macitentan or its excipients * Hemoglobin less than (\<) 80 grams per liter (g/L) * Serum aspartate (AST) and/or alanine aminotransferases (ALT) greater than (\>) 3\* upper limit of normal (ULN) * Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class (Child-Pugh score) should be fully assessed and documented in the source documents at screening Selexipag-specific: * Known allergies, hypersensitivity, or intolerance to selexipag or its excipients * Suspected or known pulmonary veno-occlusive disease (PVOD) * Uncontrolled thyroid disease * Severe coronary heart disease or unstable angina, myocardial infarction within the last 6 months, decompensated cardiac failure (if not under close medical supervision), severe arrhythmia, cerebrovascular events (for example, transient ischemic attack, stroke) within the last 3 months, or congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension (PH) * Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class (Child-Pugh score) should be fully assessed and documented in the source documents at screening * Children only: (a) Current suspicion of intussusception or ileus or gastrointestinal obstruction, per the investigator's judgment; (b) hemoglobin or hematocrit \<75 percent (%) of the lower limit of normal range Macitentan/tadalafil FDC-specific: * Known allergies, hypersensitivity, or intolerance to macitentan or tadalafil or their excipients * Hemoglobin \<80 g/L * Serum aspartate (AST) and/or alanine aminotransferases (ALT) \>3\* ULN range * Known and documented severe hepatic impairment that is, Child-Pugh Class C. For participants with hepatic impairment, Child-Pugh Class should be fully assessed and documented in the source documents at screening * Severe renal impairment (estimated glomerular filtration rate \[eGF\]/creatinine clearance \<30 milliliter per minute \[mL/min\])
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Treatment Emergent Adverse Events (TEAEs) | Baseline until End of Study (EOS) (up to 84 months) | An adverse event (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 intervention. TEAEs are defined as a treatment-emergent AE is any AE temporally associated with the use of study treatment (from start of treatment in the PLATYPUS protocol until 30 days after study treatment discontinuation) whether or not considered by the investigator as related to study treatment. |
| Frequency of TEAEs Leading to Discontinuation | Baseline until EOS (up to 84 months) | Frequency of TEAEs leading to discontinuation of study intervention will be reported. 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 intervention. TEAEs are defined as a treatment-emergent AE is any AE temporally associated with the use of study treatment (from start of treatment in the PLATYPUS protocol until 30 days after study treatment discontinuation) whether or not considered by the investigator as related to study treatment. |
| Frequency of Serious Adverse Events (SAEs) | Baseline until EOS (up to 84 months) | SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product and is medically important. |
| Frequency of Deaths | Baseline until EOS (up to 84 months) | Frequency of deaths will be reported. |
Countries
Belarus, Belgium, Bulgaria, China, Hungary, Poland, Russia, South Africa, South Korea, Taiwan, Thailand, Ukraine, Vietnam
Contacts
CONTACTStudy Contact
STUDY_DIRECTORActelion Pharmaceuticals Ltd Clinical Trial
Actelion
Outcome results
None listed