Hypertension, Pulmonary
Conditions
Brief summary
The purpose of this study is to assess the long-term safety of selexipag while providing continued selexipag treatment for participants who were previously enrolled in an Actelion-sponsored study with selexipag and who derived benefit from selexipag in indications for which a positive benefit-risk has been established.
Interventions
DRUGSelexipag
Selexipag tablets will be administered orally at all dose strengths (200, 400, 600, 800, 1000, 1200, 1400 and 1600 microgram) twice daily.
Sponsors
Actelion
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treated with selexipag at the end of a parent study and: a) the parent study has established efficacy with a favorable benefit/risk profile for the indication under investigation; b) participant may continue to benefit from treatment with selexipag; c) has completed the end of treatment (EOT) visit of the parent study; d) no alternative means of access to selexipag have been identified * Women of childbearing potential must use an acceptable method of contraception throughout the study and until at least 1 month following the last dose of study intervention * Women of childbearing potential must have a negative urine (or serum if applicable) pregnancy test at screening on Day 1 or at the last visit of the parent study * Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
Exclusion criteria
* Suspected or known pulmonary veno-occlusive disease * Known allergies, hypersensitivity, or intolerance to selexipag or its excipients * Interruption of study intervention for more than 14 days since the last dose of study intervention taken in the parent study * Female participant being pregnant, or breastfeeding, or planning to become pregnant at the time of screening and while enrolled in this study * Uncontrolled thyroid disease * Known and documented severe hepatic impairment, example, Child-Pugh Class C * Taken any disallowed therapies, Concomitant Therapy before the planned first dose of study intervention: a) treatment with a strong CYP 2C8 inhibitor (example, gemfibrozil); b) treatment with oral prostacyclin analogs (example, beraprost, treprostinil) since the last dose of study intervention taken in the parent study; c) any investigational treatment other than selexipag * 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 (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 PH
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days) | Number of participants with TEAEs were reported. Adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as AEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days. Data includes all TEAEs irrespective of whether they were serious or non-serious. |
| Number of Participants With TEAEs Leading to Premature Discontinuation of Selexipag | From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days) | Number of participants with TEAEs leading to premature discontinuation of selexipag were reported. AE was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as AEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days. |
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days) | Number of participants with TESAEs were reported. AE was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. TESAEs were defined as TSAEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days. |
| Number of Participants With Treatment-emergent Deaths | From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days) | Number of participants with treatment-emergent deaths during the study were reported. |
| Number of Pregnant Females With Maternal Exposure to Selexipag | From Day 1 up to 30 days after last dose of drug (up to 29 months) | Number of pregnant females with maternal exposure to selexipag were reported. |
Countries
Belarus, India, Romania, South Korea, Taiwan, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Selexipag Participants with pulmonary arterial hypertension (PAH) who completed the parent study AC-065A302 (NCT01106014) continued treatment with selexipag in this study (200 to 1600 micrograms \[mcg\] selexipag tablet orally twice daily \[bid\]) from Day 1 up to 28 months with the same individual maximum tolerated dose (iMTD) that they were taking at the end of their parent study. Eligible participants were then followed up for safety up to 30 days after the last dose of selexipag. | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Selexipag |
|---|---|
| Age, Continuous | 50.6 years STANDARD_DEVIATION 13.25 |
| Age, Customized >=85 years | 0 Participants |
| Age, Customized Adults (18-64 years) | 37 Participants |
| Age, Customized From 65 to 84 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Region of Enrollment BELARUS | 21 Participants |
| Region of Enrollment INDIA | 4 Participants |
| Region of Enrollment ROMANIA | 2 Participants |
| Region of Enrollment SOUTH KOREA | 4 Participants |
| Region of Enrollment TAIWAN | 3 Participants |
| Region of Enrollment UKRAINE | 9 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 43 |
| other Total, other adverse events | 20 / 43 |
| serious Total, serious adverse events | 7 / 43 |
Outcome results
Primary
Number of Participants With TEAEs Leading to Premature Discontinuation of Selexipag
Number of participants with TEAEs leading to premature discontinuation of selexipag were reported. AE was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as AEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days.
Time frame: From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With TEAEs Leading to Premature Discontinuation of Selexipag | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Number of participants with TEAEs were reported. Adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as AEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days. Data includes all TEAEs irrespective of whether they were serious or non-serious.
Time frame: From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention in this study..
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 22 Participants |
Primary
Number of Participants With Treatment-emergent Deaths
Number of participants with treatment-emergent deaths during the study were reported.
Time frame: From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Treatment-emergent Deaths | 5 Participants |
Primary
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Number of participants with TESAEs were reported. AE was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. TESAEs were defined as TSAEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days.
Time frame: From Day 1 up to 3 days after last dose of drug (up to 28 months 3 days)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 7 Participants |
Primary
Number of Pregnant Females With Maternal Exposure to Selexipag
Number of pregnant females with maternal exposure to selexipag were reported.
Time frame: From Day 1 up to 30 days after last dose of drug (up to 29 months)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention in this study. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Pregnant Females With Maternal Exposure to Selexipag | 0 Participants |