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

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02882425
• Other study ID #: AC-065-110
• Status: Completed
• Phase: Phase 1
• First received: August 18, 2016
• Last updated: February 14, 2017
• Start date: January 2015
• Est. completion date: April 2015

Study information

• Verified date: February 2017
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Selexipag 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.
• Selexipag for oral use
Tablet containing 200 µg of selexipag

Locations

Country	Name	City	State
France	Investigator Site	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

France, 

References & Publications (1)

Kaufmann P, Hurst N, Astruc B, Dingemanse J. Absolute oral bioavailability of selexipag, a novel oral prostacyclin IP receptor agonist. Eur J Clin Pharmacol. 2017 Feb;73(2):151-156. doi: 10.1007/s00228-016-2164-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)		4 days