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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Selexipag for intravenous use; Drug: Selexipag for oral use

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35042
    • Investigator site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous selexipag (Pilot phase); Subjects received a 20-minute intravenous (i.v.) infusion of 50 µg selexipag	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.; Other Names: ACT-293987
Experimental: Sequence A-B (Main phase); 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; Selexipag was reconstituted in sterile 0.9% w/v NaCl before infusion via an infusion pump at a rate of 2.5 µg/min.; Other Names: ACT-293987; Drug: Selexipag for oral use; Tablet containing 200 µg of selexipag; Other Names: ACT-293987
Experimental: Sequence B-A (Main phase); 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; Selexipag was reconstituted in sterile 0.9% w/v NaCl before infusion via an infusion pump at a rate of 2.5 µg/min.; Other Names: ACT-293987; Drug: Selexipag for oral use; Tablet containing 200 µg of selexipag; Other Names: ACT-293987

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Priska Kaufmann, PhD, Actelion

Publications and helpful links

General Publications

• 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. Epub 2016 Nov 24.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 18, 2016
• First Submitted That Met QC Criteria: August 24, 2016
• First Posted (Estimate): August 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: bioavailability; selexipag
• Additional Relevant MeSH Terms: Antihypertensive Agents; Selexipag
• Other Study ID Numbers: AC-065-110