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

• Published in: Respiratory research Vol. 22; no. 1; pp. 34 - 9
• Main Authors: Klose, Hans, Chin, Kelly M., Ewert, Ralf, Gall, Henning, Parambil, Joseph, Poch, David, Seyfarth, Hans-Jürgen, Axelsen, Lene N., Hsu Schmitz, Shu-Fang, Stein, Claudia, Preston, Ioana R.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.02.2021; BioMed Central; BMC
• Subjects: Adverse events; Blood pressure; Dosage; Drug therapy; Exposure; Hypertension; Intravenous; Intravenous administration; Metabolites; Oral administration; Patient outcomes; Patients; Pharmacokinetics; Pharmacology; Plasma; Pulmonary arterial hypertension; Pulmonary hypertension; Safety; Selexipag; Switching; Treatment interruptions; Germany; United States > US; Pulmonary arterial hypertension; Pharmacokinetics; Intravenous; Treatment interruptions; Selexipag
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-020-01594-8

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). 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. 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. 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.