Absolute Bioavailability of a Single Oral Dose of Selexipag in Healthy Subjects
- Conditions
- Healthy Subjects
- Interventions
- Registration Number
- NCT02882425
- Lead Sponsor
- Actelion
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 19
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Intravenous selexipag (Pilot phase) Selexipag for intravenous use Subjects received a 20-minute intravenous (i.v.) infusion of 50 µg selexipag Sequence A-B (Main phase) Selexipag for intravenous use 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. Sequence A-B (Main phase) Selexipag for oral use 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. Sequence B-A (Main phase) Selexipag for intravenous use 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. Sequence B-A (Main phase) Selexipag for oral use 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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
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
Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) 4 days
Trial Locations
- Locations (1)
Investigator Site
🇫🇷Rennes, France