<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03245229</url>
  </required_header>
  <id_info>
    <org_study_id>AC-080-106</org_study_id>
    <nct_id>NCT03245229</nct_id>
  </id_info>
  <brief_title>A Study in Healthy Male Subjects to Investigate Whether Administration of ACT-132577 Can Affect Rosuvastatin's Fate in the Body (Amount and Time of Presence in the Blood)</brief_title>
  <official_title>A Single-center, Open-label, One-sequence, Two-treatment Study to Investigate the Effect of ACT-132577 at Steady State on the Pharmacokinetics of Rosuvastatin in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Idorsia Pharmaceuticals Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Idorsia Pharmaceuticals Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of this study is to investigate the effect of Aprocitentan (ACT-132577)&#xD;
      at steady state on the pharmacokinetics of single-dose rosuvastatin in healthy male subjects&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 10, 2017</start_date>
  <completion_date type="Actual">September 18, 2017</completion_date>
  <primary_completion_date type="Actual">September 18, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax) of rosuvastatin</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>Cmax of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach Cmax (tmax) of rosuvastatin</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>tmax of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal half-life (t1/2) of rosuvastatin</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>t1/2 of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of rosuvastatin</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>AUC(0-t) of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)] of rosuvastatin</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>AUC(0-inf) of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profile</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trough (pre-dose) plasma concentrations (Ctrough) of ACT-132577</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>Ctrough of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profile</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events (AEs)</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>Treatment emergent adverse events and treatment emergent serious adverse events will be evaluated throughout the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in electrocardiogram (ECG) variables</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>ECG variables are to be recorded at rest using a standard 12-lead ECG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in blood pressure</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>Blood pressure (mmHg) measured using an automatic oscillometric device</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in pulse rate</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>Pulse rate (bpm) measured using an automatic oscillometric device</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the morning of Day 1, a single dose of 10 mg rosuvastatin will be administered in the fasted state followed by an observation period of 96 h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25 mg ACT-132577 will be administered o.d. from Day 5 to Day 12</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the morning of Day 13, a single dose of 10 mg rosuvastatin will be administered in the fasted state, concomitantly with 25 mg ACT-132577, followed by an observation period of 120 h.&#xD;
Doses of 25 mg ACT-132577 will be administered o.d. from Day 14 to Day 17.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aprocitentan</intervention_name>
    <description>Capsule for oral administration</description>
    <arm_group_label>Treatment B1</arm_group_label>
    <arm_group_label>Treatment B2</arm_group_label>
    <other_name>ACT-132577</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>Tablet for oral administration</description>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent in the local language prior to any study mandated procedure;&#xD;
&#xD;
          -  Healthy male subjects aged 18 to 45 years (inclusive) at screening;&#xD;
&#xD;
          -  Body mass index of 18.0 to 28.0 kg/m2 (inclusive) at screening;&#xD;
&#xD;
          -  Healthy on the basis of physical examination, cardiovascular assessments and&#xD;
             laboratory tests;&#xD;
&#xD;
          -  Hemoglobin ≥ 135 g/L at screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergic reactions or hypersensitivity to ACT-132577, rosuvastatin, any drug of&#xD;
             the same classes, or any of their excipients;&#xD;
&#xD;
          -  Any contraindication for rosuvastatin treatment;&#xD;
&#xD;
          -  History or clinical evidence of myopathy;&#xD;
&#xD;
          -  Asian or Indian-Asian ethnicity;&#xD;
&#xD;
          -  Known hypersensitivity or allergy to natural rubber latex;&#xD;
&#xD;
          -  Previous exposure to ACT-132577;&#xD;
&#xD;
          -  Treatment with rosuvastatin within 3 months prior to screening;&#xD;
&#xD;
          -  Any circumstances or conditions, which, in the opinion of the investigator, may affect&#xD;
             full participation in the study or compliance with the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Idorsia Pharmaceuticals Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cepha s.r.o</name>
      <address>
        <city>Plzen</city>
        <zip>32300</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03245229
org study id: AC-080-106
nct id: NCT03245229
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary purpose of this study is to investigate the effect of Aprocitentan (ACT-132577)
      at steady state on the pharmacokinetics of single-dose rosuvastatin in healthy male subjects
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Maximum plasma concentration (Cmax) of rosuvastatin
time frame: Up to Day 29
description: Cmax of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: Time to reach Cmax (tmax) of rosuvastatin
time frame: Up to Day 29
description: tmax of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: Terminal half-life (t1/2) of rosuvastatin
time frame: Up to Day 29
description: t1/2 of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of rosuvastatin
time frame: Up to Day 29
description: AUC(0-t) of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)] of rosuvastatin
time frame: Up to Day 29
description: AUC(0-inf) of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profile
measure: Trough (pre-dose) plasma concentrations (Ctrough) of ACT-132577
time frame: Up to Day 29
description: Ctrough of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profile
measure: Number of participants with adverse events (AEs)
time frame: Up to Day 29
description: Treatment emergent adverse events and treatment emergent serious adverse events will be evaluated throughout the study
measure: Changes from baseline in electrocardiogram (ECG) variables
time frame: Up to Day 29
description: ECG variables are to be recorded at rest using a standard 12-lead ECG
measure: Changes from baseline in blood pressure
time frame: Up to Day 29
description: Blood pressure (mmHg) measured using an automatic oscillometric device
measure: Changes from baseline in pulse rate
time frame: Up to Day 29
description: Pulse rate (bpm) measured using an automatic oscillometric device
arm group label: Treatment A
arm group type: Experimental
description: In the morning of Day 1, a single dose of 10 mg rosuvastatin will be administered in the fasted state followed by an observation period of 96 h
arm group label: Treatment B1
arm group type: Experimental
description: 25 mg ACT-132577 will be administered o.d. from Day 5 to Day 12
arm group label: Treatment B2
arm group type: Experimental
description: In the morning of Day 13, a single dose of 10 mg rosuvastatin will be administered in the fasted state, concomitantly with 25 mg ACT-132577, followed by an observation period of 120 h.
Doses of 25 mg ACT-132577 will be administered o.d. from Day 14 to Day 17.
intervention type: Drug
intervention name: Aprocitentan
description: Capsule for oral administration
arm group label: Treatment B1
arm group label: Treatment B2
other name: ACT-132577
intervention type: Drug
intervention name: Rosuvastatin
description: Tablet for oral administration
arm group label: Treatment A
arm group label: Treatment B2
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trial
role: Study Director
affiliation: Idorsia Pharmaceuticals Ltd.
facility: 
country: Czechia
responsible party type: Sponsor
mesh term: Rosuvastatin Calcium