Healthy Subjects
Conditions
Keywords
selexipag, bioavailability
Brief summary
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
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.
Interventions
DRUGSelexipag for intravenous use
Selexipag was reconstituted in sterile 0.9% w/v NaCl before infusion via an infusion pump at a rate of 2.5 µg/min.
DRUGSelexipag for oral use
Tablet containing 200 µg of selexipag
Sponsors
Actelion
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute bioavailability (F) of selexipag | From pre-dose to 72 hours post-dose | 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 |
| Area under the plasma concentration-time curve from time 0 to infinity [AUC(0-inf)] of selexipag | From pre-dose to 72 hours post-dose | AUC(0-inf) was calculated from the concentration-time profile of selexipag after both oral and intravenous administration during the main phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| time to reach maximum plasma concentration (tmax) of selexipag and its active metabolite | From pre-dose to 72 hours post-dose | 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 |
| Areas under the plasma concentration-time curve from time 0 to time t [AUC(0-t)] of selexipag and its active metabolite | From pre-dose to 72 hours post-dose | 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 |
| Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | 4 days | — |
| Terminal half-life [t(1/2)] of selexipag and its active metabolite | From pre-dose to 72 hours post-dose | 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 |
| Maximum plasma concentration (Cmax) of selexipag and its active metabolite | From pre-dose to 72 hours post-dose | 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 |
Outcome results
None listed