A Study to Evaluate ACT-132577 in Healthy Male Subjects

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to investigate the rate and routes (urine and feces) of elimination of ACT-132577, and the mass balance in urine and feces

Official Title
-----------------
Single-center, Open-label Study With 14C-radiolabeled ACT-132577 to Investigate the Mass Balance, Pharmacokinetics, and Metabolism Following Single Oral Administration to Healthy Male Subjects

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: 14C-radiolabeled ACT-132577


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent in a language understandable to the subject prior to any study-mandated procedure; Healthy male subjects aged between 45 and 65 years (inclusive) at screening; Body mass index of 18.0 to 28.0 kg/m2 (inclusive) at screening; Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests. Exclusion Criteria: Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) > 3 × upper limit of normal range at screening; Hemoglobin < 100 g/L at screening; Known hypersensitivity to ACT-132577 or drugs of the same class, or any excipient of the ACT-132577 drug formulation; Known hypersensitivity or allergy to natural rubber latex; Previous exposure to ACT-132577; Treatment with another investigational drug within 3 months prior to screening or participation in more than 4 investigational drug studies within 1 year prior to screening; Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol; A radiation burden of > 0.1 milliSievert (mSv) and ≤ 1.0 mSv in the period of 1 year prior to screening; a radiation burden of ≥ 1.1 mSv and ≤ 2.0 mSv in the period of 2 years prior to screening, etc. (add 1 year per 1 mSv).

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 14C-radiolabelled ACT-132577<br>On Day 1, subjects will receive a single oral dose of 25 mg 14C-radiolabeled ACT-132577, administered as an oral formulation in the fasted state | Drug: 14C-radiolabeled ACT-132577<br>* Single oral dose of 3.7 megabecquerel (MBq) (100 microcurie [μCi]) 14C-radiolabeled ACT-132577 administered as 1 capsule of 25 mg<br>* Other names: Aprocitentan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative excretion of radioactivity in urine and feces | 14C-radioactivity will be measured daily in urine and feces samples for determination of total radioactivity recovery | From study treatment administration up to day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with treatment-emergent adverse events and serious adverse events | Collection of any adverse event at each dose level | From study treatment administration up to day 32 | 
| Maximum plasma concentration (Cmax) of 14C-radiolabeled ACT-132577 | Cmax is directly derived from the observed plasma concentrations of ACT-132577 and its metabolites | From study treatment administration up to day 15 | 
| Time to reach Cmax (tmax) of 14C-radiolabeled ACT-132577 | tmax is directly derived from the observed plasma concentrations of ACT-132577 and its metabolites | From study treatment administration up to day 15 | 
| Terminal half-life (t1/2) of 14C-radiolabeled ACT-132577 | t1/2 is calculated from the terminal rate constant obtained from the plasma concentrations-time curves of ACT-132577 and its metabolites | From study treatment administration up to day 15 | 
| Area under the plasma concentration-time curve (AUC) of 14C-radiolabeled ACT-132577 | AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification and from zero to infinity | From study treatment administration up to day 15 | 
| Maximum plasma concentration (Cmax) of ACT-132577 and its metabolites | Cmax is directly derived from the observed plasma concentrations of ACT-132577 and its metabolites | From study treatment administration up to day 15 | 
| Time to reach Cmax (tmax) of ACT-132577 and its metabolites | tmax is directly derived from the observed plasma concentrations of ACT-132577 and its metabolites | From study treatment administration up to day 15 | 
| Terminal half-life (t1/2) of ACT-132577 and its metabolites | t1/2 is calculated from the terminal rate constant obtained from the plasma concentrations-time curves of ACT-132577 and its metabolites | From study treatment administration up to day 15 | 
| Area under the plasma concentration-time curve (AUC) ACT-132577 and its metabolites | AUC is defined for the time intervals from zero to time t of the last measured concentration above the limit of quantification and from zero to infinity | From study treatment administration up to day 15 |