Absolute Bioavailability of a Single Oral Dose of Selexipag in Healthy Subjects

Study Overview
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Brief Summary
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The primary purpose of this phase 1 study is to investigate the absolute bio-availability of a single oral dose of selexipag, i.e., to assess the amount of selexipag which reaches the blood when administered as an oral tablet (ACT-293987) compared to an intravenous administration in healthy subjects.

Detailed Description
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A pilot phase was conducted in 3 male subjects before the main phase for assessment of absolute bio-availability conducted in 16 other male subjects. The pilot phase aimed to determine the intravenous dose to be used in the main phase based on safety data and pharmacokinetics data.

Official Title
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Single-center, Open-label, Phase 1 Study Consisting of a Single-dose Pilot Phase and a Randomized, Two-way Crossover, Single-dose Main Phase to Investigate the Absolute Bioavailability of a Single Oral Dose of Selexipag in Healthy Male Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Selexipag for intravenous use
* Drug: Selexipag for oral use


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to any study-mandated procedure Aged from 18 to 45 (inclusive) at screening Body mass index (BMI) from 18.0 to 28.0 kg/m2 (inclusive) at screening Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests Exclusion Criteria: Any contraindication to the study drug formulations History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous selexipag (Pilot phase)<br>Subjects received a 20-minute intravenous (i.v.) infusion of 50 µg selexipag | Drug: Selexipag for intravenous use<br>* Selexipag was reconstituted in sterile 0.9% w/v NaCl before infusion via an infusion pump at a rate of 2.5 µg/min.<br>* Other names: ACT-293987;|
| Experimental: Sequence A-B (Main phase)<br>Subjects received a 80-minute i.v. infusion of 200 µg selexipag during Period 1, and 2 tablets of oral selexipag (total dose of 400 µg) as a single administration during Period 2. A washout period of 7 to 10 days separated the i.v. infusion from the oral administration. | Drug: Selexipag for intravenous use<br>* Selexipag was reconstituted in sterile 0.9% w/v NaCl before infusion via an infusion pump at a rate of 2.5 µg/min.<br>* Other names: ACT-293987;Drug: Selexipag for oral use<br>* Tablet containing 200 µg of selexipag<br>* Other names: ACT-293987;|
| Experimental: Sequence B-A (Main phase)<br>Subjects received 2 tablets of oral selexipag (total dose of 400 µg) as a single administration during Period 1, and a 80-minute i.v. infusion of 200 µg selexipag during Period 2. A washout period of 7 to 10 days separated the oral administration from the i.v. infusion. | Drug: Selexipag for intravenous use<br>* Selexipag was reconstituted in sterile 0.9% w/v NaCl before infusion via an infusion pump at a rate of 2.5 µg/min.<br>* Other names: ACT-293987;Drug: Selexipag for oral use<br>* Tablet containing 200 µg of selexipag<br>* Other names: ACT-293987;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute bioavailability (F) of selexipag | F was calculated using the areas under the plasma concentrations curves extrapolated to infinity [AUC(0-inf)] after oral (po) and intravenous (iv) doses, obtained during the main phase, and using the following formula: AUC(0-inf)po * iv dose / AUC(0-inf)iv * oral dose | From pre-dose to 72 hours post-dose | 
| Area under the plasma concentration-time curve from time 0 to infinity [AUC(0-inf)] of selexipag | AUC(0-inf) was calculated from the concentration-time profile of selexipag after both oral and intravenous administration during the main phase | From pre-dose to 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Areas under the plasma concentration-time curve from time 0 to time t [AUC(0-t)] of selexipag and its active metabolite | AUC from time 0 to time t of the last measured concentration above the limit of quantification [AUC(0-t)] were calculated for selexipag and its active metabolite, from their respective concentration-time profiles, after both intravenous (pilot phase and main phase) and oral administration (main phase) of selexipag | From pre-dose to 72 hours post-dose | 
| Maximum plasma concentration (Cmax) of selexipag and its active metabolite | Cmax of selexipag and its active metabolite were directly obtained from the plasma concentration-time curves after both intravenous (pilot phase and main phase) and oral administration (main phase) of selexipag | From pre-dose to 72 hours post-dose | 
| time to reach maximum plasma concentration (tmax) of selexipag and its active metabolite | tmax of selexipag and its active metabolite were directly obtained from the plasma concentration-time curves after both intravenous (pilot phase and main phase) and oral administration (main phase) of selexipag | From pre-dose to 72 hours post-dose | 
| Terminal half-life [t(1/2)] of selexipag and its active metabolite | t(1/2) of selexipag and its active metabolite were calculated after both intravenous (pilot phase and main phase) and oral administration (main phase) of selexipag from the concentration-time profiles | From pre-dose to 72 hours post-dose | 
| Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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selexipag, bioavailability