Pulmonary Arterial Hypertension
Conditions
Keywords
switch, intravenous, selexipag
Brief summary
The development of selexipag for intravenous administration will be useful to avoid treatment interruptions in patients with pulmonary arterial hypertension (PAH) already treated with selexipag administered orally as tablets (Uptravi®). The target population for intravenous selexipag includes those PAH patients who are hospitalized and are unable to swallow tablets of Uptravi. The primary objective of this study is to assess whether it is safe for patients with PAH to temporarily change from selexipag tablets (Uptravi®) to selexipag given directly into a vein (intravenous selexipag), and then switching back to the initial oral dose of selexipag.
Detailed description
After screening (Visit 1), each subject will participate in the following consecutive treatment periods: Period 1(treatment with oral selexipag at Visit 2/Day 1), Period 2 (treatment with intravenous selexipag at Visit 2/ Day 2 and Day 3), Period 3 (treatment with oral selexipag starting in the evening of Visit 2/Day 3 and ending 7 to 11 days later at Visit 3). Then a safety follow-up period is planned up to end of study visit (EOS), which occurs between Day 33 and Day 40.
Interventions
DRUGi.v. selexipag
Selexipag for intravenous administration, twice daily as an infusion over 87 min. The dose is individualized for each subject to correspond to his/her current oral dose of Uptravi®.
DRUGoral selexipag (Uptravi)
Uptravi is used as an auxiliary medicinal product, as part of the PAH standard treatment and administered according to the local prescribing information
Sponsors
Actelion
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form prior to any study-mandated procedure. * Male and female subjects aged from 18 to 75 years (inclusive), * Subjects with stable pulmonary arterial hypertension (PAH) defined as WHO Functional Class I-III at Visit 1 and Visit 2, and no change (i.e., introduction or dose change) in PAH-specific medication (i.e., ERA, PDE-5 inhibitor or sGC stimulator) and diuretics in the last 28 days prior to Visit 2. * Subjects currently treated with Uptravi® at a stable dose (i.e. unchanged dose) for at least 28 days before Visit 2. * Women of childbearing potential must have a negative pregnancy test at Visit 1 (screening) and Visit 2.
Exclusion criteria
* Pregnant, planning to become pregnant or lactating. * Known and documented moderate or severe hepatic impairment. * Subjects having received gemfibrozil at any time since initiation of Uptravi®. * Treatment with any prostacyclin and prostacyclin analogs within 28 days prior to Visit 1. * SBP \< 90 mmHg at Visit 1 or at Visit 2. * Known or suspected uncontrolled hyperthyroidism. * Severe renal failure and ongoing or planned dialysis. * Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results. * Known concomitant life-threatening disease with a life expectancy \< 12 months. * Treatment with another investigational treatment within 3 months of Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Adverse Event (AE) | From Day 1 to Day 37 | AE is any untoward medical event that occurs in a participant during the course of the study whether or not considered by the investigator as related to the study treatment. |
| Number of Participants With Prostacyclin-associated Adverse Events | From Day 1 to Day 37 | Prostacyclin-associated AE include headache, diarrhea, nausea, vomiting, jaw pain, myalgia, pain in the extremity, flushing and arthralgia. |
| Number of Participants With Adverse Event Related to Injection Site Reactions | From Day 2 to Day 3 | This is the number of participants with at least one clinically significant reaction at the injection site (e.g., erythema/redness, tenderness, swelling, induration, hemorrhage at the injection site) occurring on the days of intravenous (iv) selexipag injection. |
| Number of Participants With Prostacyclin-associated AEs Leading to Study Treatment Discontinuation | From Day 2 to Day 3 | This is the number of subjects who discontinued the i.v. selexipag treatment due to prostacyclin-associated adverse events (headache, diarrhea, nausea, vomiting, jaw pain, myalgia, pain in the extremity, flushing and arthralgia). |
| Number of Participants With PAH-related Adverse Events | From Day 1 to Day 37 | This is the number of participants with at least one AE considered to be related to pulmonary arterial hypertension during the course of the study. |
Countries
Germany, United States
Participant flow
Recruitment details
Twenty-two patients treated with Uptravi for pulmonary arterial hypertension (PAH) were screened; 20 of them were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Selexipag Subjects treated with a stable dose of oral selexipag (Uptravi) between 200 and 1600 ug twice daily continued to take Uptravi at their prescribed dose during Period 1 (Day 1), then they were switched to intravenous (iv) selexipag during period 2 (3 doses, Day 2 & Day 3) and back to Uptravi during Period 3 | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Selexipag |
|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 9.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| PAH etiology at baseline Associated with CHD | 1 Participants |
| PAH etiology at baseline Associated with CTD | 4 Participants |
| PAH etiology at baseline Associated with HIV | 0 Participants |
| PAH etiology at baseline Associated with portal hypertension | 1 Participants |
| PAH etiology at baseline Associated with schistosomiasis | 0 Participants |
| PAH etiology at baseline Drug or toxin induced PAH | 0 Participants |
| PAH etiology at baseline Heritable PAH | 1 Participants |
| PAH etiology at baseline Idiopathic PAH | 13 Participants |
| PAH-specific therapies at baseline ERA + PDE5-inhibitors | 13 Participants |
| PAH-specific therapies at baseline ERA + sGC stimulator | 5 Participants |
| PAH-specific therapies at baseline PDE-5 inhibitors | 1 Participants |
| PAH-specific therapies at baseline sGC stimulator | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White | 19 Participants |
| Region of Enrollment Germany | 13 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 4 Participants |
| Uptravi dose at screening 1000 ug twice daily | 3 Participants |
| Uptravi dose at screening 1200 ug twice daily | 2 Participants |
| Uptravi dose at screening 1400 ug twice daily | 1 Participants |
| Uptravi dose at screening 1600 ug twice daily | 9 Participants |
| Uptravi dose at screening 200 ug twice daily | 0 Participants |
| Uptravi dose at screening 400 ug twice daily | 1 Participants |
| Uptravi dose at screening 600 ug twice daily | 2 Participants |
| Uptravi dose at screening 800 ug twice daily | 2 Participants |
| World Health Organization Functional classes (WHO FC) FC I | 1 Participants |
| World Health Organization Functional classes (WHO FC) FC II | 13 Participants |
| World Health Organization Functional classes (WHO FC) FC III | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 13 / 20 |
| serious Total, serious adverse events | 2 / 20 |
Outcome results
Primary
Number of Participants With Adverse Event Related to Injection Site Reactions
This is the number of participants with at least one clinically significant reaction at the injection site (e.g., erythema/redness, tenderness, swelling, induration, hemorrhage at the injection site) occurring on the days of intravenous (iv) selexipag injection.
Time frame: From Day 2 to Day 3
Population: iv safety analysis set including all enrolled subjects who received at least one dose of intravenous selexipag during Period 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Adverse Event Related to Injection Site Reactions | 2 Participants |
Primary
Number of Participants With at Least One Adverse Event (AE)
AE is any untoward medical event that occurs in a participant during the course of the study whether or not considered by the investigator as related to the study treatment.
Time frame: From Day 1 to Day 37
Population: Safety analysis set including all enrolled subjects who received at least one dose of Uptravi or intravenous selexipag during any of the study periods
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With at Least One Adverse Event (AE) | 15 Participants |
Primary
Number of Participants With PAH-related Adverse Events
This is the number of participants with at least one AE considered to be related to pulmonary arterial hypertension during the course of the study.
Time frame: From Day 1 to Day 37
Population: Safety analysis set including all enrolled subjects who received at least one dose of Uptravi or intravenous selexipag during any of the study periods
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With PAH-related Adverse Events | 3 Participants |
Primary
Number of Participants With Prostacyclin-associated Adverse Events
Prostacyclin-associated AE include headache, diarrhea, nausea, vomiting, jaw pain, myalgia, pain in the extremity, flushing and arthralgia.
Time frame: From Day 1 to Day 37
Population: Safety analysis set including all enrolled subjects who received at least one dose of Uptravi or intravenous selexipag during any of the study periods
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Prostacyclin-associated Adverse Events | 7 Participants |
Primary
Number of Participants With Prostacyclin-associated AEs Leading to Study Treatment Discontinuation
This is the number of subjects who discontinued the i.v. selexipag treatment due to prostacyclin-associated adverse events (headache, diarrhea, nausea, vomiting, jaw pain, myalgia, pain in the extremity, flushing and arthralgia).
Time frame: From Day 2 to Day 3
Population: iv safety analysis set including all enrolled subjects who received at least one dose of intravenous selexipag during period 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Prostacyclin-associated AEs Leading to Study Treatment Discontinuation | 0 Participants |