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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-004035-21 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Selexipag | Experimental | Subjects with stable pulmonary arterial hypertension (PAH) and currently treated with a stable oral dose of Uptravi will be switched to i.v. selexipag from Day 2 to Day 3 (2 infusions on Day 2 and 1 infusion on Day 3). Otherwise, they will continue with their current oral selexipag treatment throughout the study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| i.v. selexipag | Drug | 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®. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From Day 1 to Day 37 |
| 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. | From Day 1 to Day 37 |
| 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. | From Day 2 to Day 3 |
| 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). | From Day 2 to Day 3 |
| 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. | From Day 1 to Day 37 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ralph Preiss | Actelion | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Diego Medical center - PULM VASCULAR DIV | La Jolla | California | 92037 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33536021 | Derived | Klose H, Chin KM, Ewert R, Gall H, Parambil J, Poch D, Seyfarth HJ, Axelsen LN, Hsu Schmitz SF, Stein C, Preston IR. Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension: safety, tolerability, and pharmacokinetic results from an open-label, phase III study. Respir Res. 2021 Feb 3;22(1):34. doi: 10.1186/s12931-020-01594-8. |
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Twenty-two patients treated with Uptravi for pulmonary arterial hypertension (PAH) were screened; 20 of them were enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 (Oral Selexipag) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 27, 2017 | Apr 19, 2019 |
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| oral selexipag (Uptravi) | Drug | Uptravi is used as an auxiliary medicinal product, as part of the PAH standard treatment and administered according to the local prescribing information |
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| TUFTS New England Medical Center - PULM / CRITICAL CARE & SLEEP |
| Boston |
| Massachusetts |
| 02111-1552 |
| United States |
| Cleveland Clin Foundation - Dept of Pulm & Critical Care Med | Cleveland | Ohio | 44195 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390-8550 | United States |
| Universitätsklinikum Giessen und Marburg GmbH, Medizinische Klinik und Poliklinik II, Pneumologie | Giessen | 35392 | Germany |
| Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin B | Greifswald | 17475 | Germany |
| Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik, Pneumologie | Hamburg | 20246 | Germany |
| Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Pneumologie | Leipzig | 04103 | Germany |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 (Intravenous Selexipag) |
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| Period 3 (Oral Selexipag) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| World Health Organization Functional classes (WHO FC) | The WHO FC describes the severity of PAH symptoms. It ranges from FC I (no symptoms due to ordinary physical activity) to FC IV (severe symptoms with any activity or at rest). Only PAH patients with WHO FC I, II or III at screening and baseline visits could be enrolled. | Count of Participants | Participants |
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| Uptravi dose at screening | Count of Participants | Participants |
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| PAH-specific therapies at baseline | The following PAH-specific therapies were allowed on top of Uptravi at baseline: endothelin receptor antagonists (ERA), phosphodiesterase type-5 (PDE5) inhibitors and soluble guanylate cyclase (sGC) stimulators | Count of Participants | Participants |
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| PAH etiology at baseline | Patients with the following types of pulmonary arterial hypertension (PAH) could be enrolled: idiopathic PAH, heritable PAH, PAH associated with another disease or condition, including connective tissue disease (CTD), congenital heart disease (CHD), HIV infection, portal hypertension, schistosomiasis) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety analysis set including all enrolled subjects who received at least one dose of Uptravi or intravenous selexipag during any of the study periods | Posted | Count of Participants | Participants | From Day 1 to Day 37 |
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|
| ||||||||||||||||||||||||||
| 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. | Safety analysis set including all enrolled subjects who received at least one dose of Uptravi or intravenous selexipag during any of the study periods | Posted | Count of Participants | Participants | From Day 1 to Day 37 |
|
| |||||||||||||||||||||||||||
| 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. | iv safety analysis set including all enrolled subjects who received at least one dose of intravenous selexipag during Period 2 | Posted | Count of Participants | Participants | From Day 2 to Day 3 |
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| |||||||||||||||||||||||||||
| 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). | iv safety analysis set including all enrolled subjects who received at least one dose of intravenous selexipag during period 2 | Posted | Count of Participants | Participants | From Day 2 to Day 3 |
|
| |||||||||||||||||||||||||||
| 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. | Safety analysis set including all enrolled subjects who received at least one dose of Uptravi or intravenous selexipag during any of the study periods | Posted | Count of Participants | Participants | From Day 1 to Day 37 |
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From Day 2 to Day 37
Treatment-emergent AEs are reported, i.e. serious and non-serious AEs starting on or after the intravenous injection of selexipag, which is the investigational treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 0 | 20 | 2 | 20 | 13 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right Ventricular Failure | Cardiac disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Blindness Unilateral | Eye disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Rhegmatogenous Retinal Detachment | Eye disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Infusion Site Erythema | General disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Infusion Site Swelling | General disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Oedema Peripheral | General disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA Version 21.0 | Non-systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 21.0 | Non-systematic Assessment |
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| Incorrect Drug Administration Rate | Injury, poisoning and procedural complications | MedDRA Version 21.0 | Non-systematic Assessment |
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| Vascular Access Complication | Injury, poisoning and procedural complications | MedDRA Version 21.0 | Non-systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Pain in Jaw | Musculoskeletal and connective tissue disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Tension Headache | Nervous system disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Chromaturia | Renal and urinary disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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| Flushing | Vascular disorders | MedDRA Version 21.0 | Non-systematic Assessment |
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Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation at a congress. Upon review, Actelion may provide comments and may also request alterations and/or deletions for the sole purpose of protecting its confidential information or patent rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| clinical trial disclosure desk | Actelion Pharmaceuticals Ltd | 0041615656565 | clinical-trials-disclosure@its.jnj.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 2, 2018 | Apr 19, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C523468 | selexipag |
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| Unknown or Not Reported |
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| American Indian or Alaska Native |
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| Native Hawaiian or other Pacific Islander |
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| White |
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| Other |
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| FC III |
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| 600 ug twice daily |
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| 800 ug twice daily |
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| 1000 ug twice daily |
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| 1200 ug twice daily |
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| 1400 ug twice daily |
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| 1600 ug twice daily |
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| ERA + PDE5-inhibitors |
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| ERA + sGC stimulator |
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| Drug or toxin induced PAH |
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| Associated with CTD |
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| Associated with CHD |
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| Associated with HIV |
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| Associated with portal hypertension |
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| Associated with schistosomiasis |
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