Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02471183 | Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension | PHASE3 | COMPLETED | 34 | — | — | Oct 12, 2015 | Dec 5, 2016 | Jan 23, 2018 | 15 | United States |
| NCT01106014 | Selexipag (ACT-293987) in Pulmonary Arterial Hypertension | PHASE3 | COMPLETED | 1,156 | — | — | Dec 1, 2009 | Oct 1, 2014 | Oct 27, 2025 | 182 | United States, Argentina +37 |
| NCT03492177 | A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension | PHASE2 | ACTIVE NOT_RECRUITING | 63 | — | — | Jul 23, 2018 | Dec 31, 2026 | Jun 5, 2026 | 34 | United States, Belarus +14 |
A sustained treatment transition is considered if the 3 following criteria are met a) being on study treatment (selexipag) at Week 16, and b) not having a study treatment interruption(s) of a total of 8 days or more prior to Week 16, and c) absence of inhaled treprostinil or any prostanoid treatment after Week 8 up to Week 16. The percentage of subjects with a sustained treatment transition is calculated with 95% confidence interval (CI) using the Clopper-Pearson method.
Percentage of subjects with treatment-emergent AEs (serious and non serious), regardless of relationship to selexipag
Number of subjects with adverse events leading to premature discontinuation of selexipag is determined from the first dose of selexipag up to the last dose of selexipag
Both systolic(SBP) and diastolic (DBP) arterial blood pressure were measured in a sitting position after at least 5 minutes of rest at scheduled time points. Median change from baseline to pre-specified post-baseline visits are calculated
Pulse rate is measured after at least 5 minutes of rest in a sitting position. Median change from baseline to pre-specified post-baseline visits are calculated.
This is the individual maximal tolerated dose (MTD) observed at Week 12 in the subjects still on selexipag at Week 16. MTD is defined as the dose of selexipag reached with the last dose change up to Week 12
Median time from baseline (Day1) to the end of down-titration of inhaled treprostinil is calculated
Time from randomization to the first occurrence of a morbidity event or death (all causes) was analyzed with the Kaplan-Meier method (event-free KM estimates at different time points). Morbidity event was defined as any of the following events confirmed by the Critical Event committee: * Hospitalization for worsening of pulmonary arterial hypertension (PAH), * Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy, * Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to worsening of PAH, * Disease progression which was defined by a decrease in 6-minute walk distance from baseline (\>=15%, confirmed by a 2nd test on a different day) combined with worsening of WHO FC for patients belonging to WHO FC II/III at baseline, or combined with the need for additional PAH-specific therapy for patients belonging to WHO FC III/IV at baseline. Note: The number of patients at risk decreased over time but this cannot be captured below
AUCτ, ss, combined was defined as the area under the plasma concentration-time curve over one dosing interval at steady state. AUCτ,ss,combined was calculated as 1/38 AUCτ,ss,selexipag plus 37/38 AUCτ,ss,ACT-333679.
| Arm | Type | Description |
|---|---|---|
| Selexipag, Open Label | EXPERIMENTAL | Subjects on inhaled treprostinil treatment participate in a 16-week main treatment period including down-titration of treprostinil to end of Week 8 and parallel up-titration of selexipag to the maximum tolerated dose (MTD) up to Week 12, for each individual patient but not above 1600 mcg twice daily. From Week 12 up to Week 16, patients continue selexipag at their individual MTD. Patients could continue the study drug selexipag during the extended treatment period from Week 16 until commercial availability of selexipag. |
| 1 | EXPERIMENTAL | Selexipag is up-titrated from Day 1 to Week 12 to each patient's maximum tolerated dose in the range of 200-1600 µg twice a day (b.i.d.) in 200 µg steps starting with one 200 µg oral tablet on Day 1. From Day 2 onwards, a b.i.d. dose regimen with an interval of approximately 12 hours is followed. If this dose (selexipag 200 μg b.i.d.) is well-tolerated, selexipag is up-titrated with weekly increments of 200 µg. Up-titration is followed by a stable maintenance treatment period from Week 12 onwards, up to Week 26, at the maximum tolerated dose |
| 2 | PLACEBO_COMPARATOR | Matching placebo is administered orally with a dosing interval of approximately12 h. A (mock) up-titration scheme is followed |
| open label selexipag | EXPERIMENTAL | The first dose of selexipag (Uptravi) will be administered in the evening of Day 1 and will be based on the body weight. Thereafter selexipag will be administered twice daily (morning and evening). Selexipag will be up-titrated during the first 12 weeks, with weekly increments equal to the starting dose until the participants reach their individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline weight category is achieved (which will be 8-fold of the corresponding starting dose). Up-titration is followed by a stable maintenance treatment period from Week 12 to Week 16, at the maximum tolerated dose. Thereafter, participants will be treated with selexipag as long as the treatment is beneficial to the participants, as per investigator's decision. |
| Name | Type | Description |
|---|---|---|
| Selexipag | DRUG | Tablets for oral administration containing 200 micrograms (mcg) of selexipag to be administered twice a day. The individual dose is to be established during the first 12 weeks of the study. Doses are in the range from 200 micrograms (1 tablet) to 1,600 micrograms (8 tablets). |
| Placebo | DRUG | Placebo tablets matching selexipag |
| selexipag (Uptravi) | DRUG | Film-coated tablets for oral administration |
Inclusion Criteria: * Male and female patients aged from 18 to 75 years (inclusive) with pulmonary arterial hypertension (PAH). * Etiology of PAH belonging to one of the following subgroups: idiopathic PAH, Heritable PAH, drug or toxin induced, associated with connective tissue disease, associated ...