Clinical trial NCT02206295: Study in Healthy Male Subjects to Demonstrate Bioequivalence of 1600 μg Selexipag Administered as Eight Tablets of 200 μg or as Single Tablet of 1600 μg
Official title: A Single-center, Open-label, Randomized, Two-period, Two-treatment, Crossover Study in Healthy Male Subjects to Demonstrate Bioequivalence of 1600 μg Selexipag Administered as Eight Tablets of 200 μg (Reference Drug) or as Single Tablet of 1600 μg (Test Drug)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioequivalence
Keywords: selexipag
ACT-333679
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2014-08-01
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The primary aim of this study is to demonstrate bioequivalence in the rate and extent of absorption between 1600 μg selexipag test drug (administered orally as film-coated tablets of 1600 μg, twice a day (b.i.d.) and 1600 μg selexipag reference drug (administered orally as 8 film-coated tablets of 200 μg b.i.d.) at steady-state in healthy male subjects following a multiple-dose up-titration scheme.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent in the local language prior to any study-mandated procedure.
* Healthy male subjects aged between 18 and 55 years (inclusive) at Screening.
* No clinically significant findings on the physical examination at Screening.
* Body mass index of 18.0 to 30.0 kg/m\^2 (inclusive) at Screening.
* Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (all inclusive), measured at Screening.
* 12-lead electrocardiogram without clinically relevant abnormalities, measured at Screening.
* Hematology, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at Screening.
* Negative results from urine drug screen and alcohol breath test at Screening.
* Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria:

* Known allergic reactions or hypersensitivity to selexipag or any excipient of the drug formulation used in this study.
* History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of selexipag.
* Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
* Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
* Treatment with selexipag or another investigational drug within 1 month prior to Screening or 5 half-lives, whichever is longer.
* History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to Screening.
* Excessive caffeine consumption at Screening.
* Smoking within 3 months prior to Screening and inability to refrain from smoking during the course of the study.
* Previous treatment with any prescribed medications (including vaccines) or over-the-counter medications within 2 weeks prior to first study drug administration.
* Loss of 500 mL or more of blood within 3 months prior to Screening.
* Positive results from the hepatitis serology (hepatitis B antigen and hepatitis C antibodies), except for vaccinated subjects or subjects with past but resolved hepatitis, at Screening.
* Positive results from the human immunodeficiency virus serology at Screening.
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
* Legal incapacity or limited legal capacity at Screening.

Primary outcomes:
measure: Area under the plasma concentration-time curve (AUCt) for selexipag
timeFrame: 23 days
measure: Maximum plasma concentration at steady state (Cmax,ss) for selexipag
timeFrame: 23 days
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUCt) for ACT-333679
timeFrame: 23 days
measure: Maximum plasma concentration at steady state (Cmax,ss) for ACT-333679
timeFrame: 23 days
measure: Time to reach maximum plasma concentration at steady state (tmax,ss) for selexipag
timeFrame: 23 days
measure: Trough plasma concentration at the end of one dose interval (Ctrough) for selexipag
timeFrame: 23 days
measure: Trough plasma concentration at the end of one dose interval (Ctrough) for ACT-333679
timeFrame: 23 days
measure: Trough plasma concentration at steady state (Ctrough,ss) for selexipag
timeFrame: 23 days
measure: Trough plasma concentration (Ctrough,ss) for ACT-333679
timeFrame: 23 days
measure: Change in systolic blood pressure from baseline up to end of study
timeFrame: up to 28 days
measure: Change in diastolic blood pressure from baseline up to end of study
timeFrame: up to 28 days
measure: Change in pulse rate from baseline up to end of study
timeFrame: up to 28 days
measure: Change in body weight from baseline up to end of study
timeFrame: up to 28 days
measure: Change in heart rate from baseline up to end of study
timeFrame: up to 28 days
measure: Change in PQ/PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) from baseline up to end of study
timeFrame: up to 28 days
measure: Change in QRS interval (time interval from the beginning of the Q wave to the end of the S wave) from baseline up to end of study
timeFrame: up to 28 days
measure: Change in QT interval (time interval from beginning of the Q wave until end of the T wave) from baseline up to end of study
timeFrame: up to 28 days
measure: Change in QTcB interval (time interval from beginning of the Q wave until end of the T wave, according to Bazett's correction) from baseline up to end of study
timeFrame: up to 28 days
measure: Change in QTcF interval (time interval from beginning of the Q wave until end of the T wave, according to Fridericia's correction) from baseline up to end of study
timeFrame: up to 28 days
measure: Number of treatment-emergent electrocardiogram abnormalities from baseline up to end of study
timeFrame: up to 28 days
measure: Number of participants with adverse events leading to discontinuation of study treatment
timeFrame: up to 28 days
Other outcomes:
Locations:
Study officials:
affiliation: Actelion
name: Daniela Baldoni, PhD, PharmD
role: STUDY_DIRECTOR
References: