TY - JOUR
T1 - Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension
T2 - safety, tolerability, and pharmacokinetic results from an open-label, phase III study
AU - Klose, Hans
AU - Chin, Kelly M.
AU - Ewert, Ralf
AU - Gall, Henning
AU - Parambil, Joseph
AU - Poch, David
AU - Seyfarth, Hans Jürgen
AU - Axelsen, Lene N.
AU - Hsu Schmitz, Shu Fang
AU - Stein, Claudia
AU - Preston, Ioana R.
N1 - Funding Information:
Open Access funding enabled and organized by Projekt DEAL. This study was sponsored by Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson (Allschwil, Switzerland). The sponsor was involved in the conception and design of the study, analysis and interpretation of the data, critical revision of the manuscript, and approval for submission to the journal.
Funding Information:
Medical writing assistance and editorial support were provided by Zoe Schafer PhD, of Watermeadow Medical (an Ashfield company, part of UDG Healthcare plc), and was funded by Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to the progressive nature of the disease. An intravenous (IV) formulation of selexipag was developed to provide a treatment option for short-term interruptions to oral selexipag. In this prospective, multicenter, open-label study, the safety, tolerability, and pharmacokinetics of temporarily switching between oral and IV selexipag were investigated (NCT03187678, ClinicalTrials.gov). Methods: PAH patients receiving stable oral selexipag doses were enrolled. Following three consecutive IV selexipag infusions patients resumed oral selexipag. Corresponding IV and oral doses were selected to achieve comparable exposure to the active metabolite of selexipag. Safety outcomes were monitored throughout, and pharmacokinetic samples were obtained after oral and IV administration. Results: All 20 patients completed the study. Fifteen patients had adverse events (AEs), most were mild, and none resulted in discontinuation. Headache was the most common AE throughout the study (four patients). Three serious AEs occurred in two patients with underlying comorbidities when oral dosing had resumed. There were no changes in WHO functional class for any patient and no clinically symptomatic changes in blood pressure were observed. Comparable exposure to the active metabolite of selexipag was demonstrated following corresponding oral and IV selexipag doses. Conclusions: Temporarily switching between corresponding doses of oral and IV selexipag was well-tolerated with no unexpected safety findings and comparable exposure to the active metabolite. Treatment with IV selexipag is a feasible option to bridge temporary oral selexipag treatment interruptions.
AB - Background: The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to the progressive nature of the disease. An intravenous (IV) formulation of selexipag was developed to provide a treatment option for short-term interruptions to oral selexipag. In this prospective, multicenter, open-label study, the safety, tolerability, and pharmacokinetics of temporarily switching between oral and IV selexipag were investigated (NCT03187678, ClinicalTrials.gov). Methods: PAH patients receiving stable oral selexipag doses were enrolled. Following three consecutive IV selexipag infusions patients resumed oral selexipag. Corresponding IV and oral doses were selected to achieve comparable exposure to the active metabolite of selexipag. Safety outcomes were monitored throughout, and pharmacokinetic samples were obtained after oral and IV administration. Results: All 20 patients completed the study. Fifteen patients had adverse events (AEs), most were mild, and none resulted in discontinuation. Headache was the most common AE throughout the study (four patients). Three serious AEs occurred in two patients with underlying comorbidities when oral dosing had resumed. There were no changes in WHO functional class for any patient and no clinically symptomatic changes in blood pressure were observed. Comparable exposure to the active metabolite of selexipag was demonstrated following corresponding oral and IV selexipag doses. Conclusions: Temporarily switching between corresponding doses of oral and IV selexipag was well-tolerated with no unexpected safety findings and comparable exposure to the active metabolite. Treatment with IV selexipag is a feasible option to bridge temporary oral selexipag treatment interruptions.
KW - Intravenous
KW - Pharmacokinetics
KW - Pulmonary arterial hypertension
KW - Selexipag
KW - Treatment interruptions
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U2 - 10.1186/s12931-020-01594-8
DO - 10.1186/s12931-020-01594-8
M3 - Article
C2 - 33536021
AN - SCOPUS:85100406845
SN - 1465-9921
VL - 22
JO - Respiratory Research
JF - Respiratory Research
IS - 1
M1 - 34
ER -