<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/NCT04406896</url>
  </required_header>
  <id_info>
    <org_study_id>ID-076-108</org_study_id>
    <secondary_id>2020-001315-25</secondary_id>
    <nct_id>NCT04406896</nct_id>
  </id_info>
  <brief_title>The Effect of Reduced Liver Function on Selatogrel Pharmacokinetics</brief_title>
  <official_title>An Open-label, Single-dose, Phase 1 Study to Evaluate the Pharmacokinetics of Selatogrel in Subjects With Mild and Moderate Hepatic Impairment Compared to Matched Healthy 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>
      This is a prospective, single-center, open-label, single-dose, Phase 1 study, to assess the&#xD;
      effect of mild and moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics&#xD;
      of selatogrel (ACT-246475).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 22, 2020</start_date>
  <completion_date type="Actual">October 23, 2020</completion_date>
  <primary_completion_date type="Actual">October 23, 2020</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Moderate hepatic impaired participants will be dosed after an interim analysis of at least 6 participants with mild hepatic impairment. Healthy participants will be matched to hepatic impaired participants.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The maximum plasma concentration (Cmax) of selatogrel</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach Cmax (tmax)</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curves (AUC0-t) of selatogrel</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The area under the plasma concentration-time curve from zero to infinity (AUC0-inf) of selatogrel</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal half-life (t½) of selatogrel</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The apparent clearance (CL/F) of selatogrel</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The apparent volume of distribution (Vz/F) of selatogrel</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma protein binding of selatogrel</measure>
    <time_frame>Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose and post-dose).</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in supine blood pressure</measure>
    <time_frame>Multiple predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in temperature</measure>
    <time_frame>Multiple predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in pulse rate</measure>
    <time_frame>Multiple predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in body weight</measure>
    <time_frame>Multiple predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in clinical laboratory tests</measure>
    <time_frame>Multiple predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline at each time point of measurement in ECG variables.</measure>
    <time_frame>Multiple predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhibition of platelet aggregation</measure>
    <time_frame>Multiple predefined times on Day 1 (pre-dose) up to Day 3.</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Subjects</condition>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Participants with mild hepatic impairment (Group 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant with Child-Pugh Grade A Score of 5-6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Participants with moderate hepatic impairment (Group 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant with moderate hepatic impairment with a Child-Pugh Grade B Score of 7-9.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy participants (Group 3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selatogrel</intervention_name>
    <description>A single subcutaneous injection of 16 mg.</description>
    <arm_group_label>Healthy participants (Group 3)</arm_group_label>
    <arm_group_label>Participants with mild hepatic impairment (Group 1)</arm_group_label>
    <arm_group_label>Participants with moderate hepatic impairment (Group 2)</arm_group_label>
    <other_name>ACT-246475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All participants (Groups 1,2 and 3)&#xD;
&#xD;
          -  Signed informed consent in a language understandable to the participant prior to any&#xD;
             study-mandated procedure.&#xD;
&#xD;
          -  Male or female participant aged between 18 and 79 years (inclusive) at screening.&#xD;
&#xD;
          -  Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test at screening&#xD;
             and a negative urine pregnancy test on Day 1 (pre-dose). They must consistently and&#xD;
             correctly use (from screening, during the entire study, and for at least 30 days after&#xD;
             last study treatment administration) an acceptable effective method of contraception&#xD;
             method, be sexually inactive, or have a vasectomized partner. If a hormonal&#xD;
             contraceptive is used, it must have been initiated at least 1 month before treatment&#xD;
             administration.&#xD;
&#xD;
          -  Women of non-childbearing potential.&#xD;
&#xD;
        Additional principal inclusion criteria for participants with hepatic impairment (Groups 1&#xD;
        and 2)&#xD;
&#xD;
          -  Hepatic impairment due to liver cirrhosis according to the Child-Pugh classification:&#xD;
&#xD;
               -  Group 1: Mild hepatic impairment, Child-Pugh A = score 5-6.&#xD;
&#xD;
               -  Group 2: Moderate hepatic impairment, Child-Pugh B = score 7-9.&#xD;
&#xD;
          -  Systolic blood pressure (SBP) 95-160 mmHg, diastolic blood pressure (DBP) 60-95 mmHg,&#xD;
             and pulse rate 50-100 bpm (inclusive), measured on the same arm, after 5 minutes in&#xD;
             the supine position at screening and on Day 1 (pre-dose).&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) at screening using the Modification of&#xD;
             Diet in Renal Disease (MDRD) formula of:&#xD;
&#xD;
               -  greater than or equal to 60 mL/min/1.73 m2 for participants with mild hepatic&#xD;
                  impairment (Group 1)&#xD;
&#xD;
               -  greater than or equal to 45 mL/min/1.73 m2 for participants with moderate hepatic&#xD;
                  impairment (Group 2).&#xD;
&#xD;
          -  Stable concomitant medications for at least 3 weeks prior to screening and up to Day 1&#xD;
             and expected to be stable during the conduct of the study.&#xD;
&#xD;
        Additional principal inclusion criteria for healthy participants (Group 3)&#xD;
&#xD;
          -  Normal blood pressure measured on the same arm, after 5 minutes in the supine position&#xD;
             at screening and on Day 1 pre-dose defined as:&#xD;
&#xD;
               -  SBP 90 to 140 mmHg, DBP 60 to 90 mmHg, and pulse rate 50 to 100 bpm (inclusive)&#xD;
                  for participants less than 60 years of age.&#xD;
&#xD;
               -  SBP 95 to 160 mmHg, DBP 65 to 95 mmHg, and pulse rate 50 to 100 bpm (inclusive)&#xD;
                  for participants 60 years and older.&#xD;
&#xD;
          -  eGFR greater than or equal to 80 mL/min/1.73 m2 at screening using the MDRD formula.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All participants (Groups 1, 2 and 3)&#xD;
&#xD;
          -  Pregnant or lactating woman.&#xD;
&#xD;
          -  Previous exposure to selatogrel.&#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;
&#xD;
          -  Known hypersensitivity to P2Y12 receptor antagonists or any excipients of the drug&#xD;
             formulation.&#xD;
&#xD;
          -  Known platelet disorders.&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity at screening.&#xD;
&#xD;
        Additional exclusion criteria for participants with hepatic impairment (Groups 1 and 2)&#xD;
&#xD;
          -  History or clinical evidence of any disease and/or existence of any surgical or&#xD;
             medical condition (e.g., cholecystectomy), which might interfere with the absorption,&#xD;
             distribution, metabolism, and excretion (ADME) of the study treatment (except for&#xD;
             hepatic impairment, appendectomy, and herniotomy).&#xD;
&#xD;
          -  Acute hepatitis, hepatic cancer, primary biliary cirrhosis, or any form of cholestatic&#xD;
             disease.&#xD;
&#xD;
          -  Clinical evidence or suspected acute liver failure as judged by the investigator.&#xD;
&#xD;
          -  Severe ascites and/or pleural effusion.&#xD;
&#xD;
          -  Encephalopathy greater than grade 2.&#xD;
&#xD;
          -  Clinical evidence of current alcohol or drug abuse.&#xD;
&#xD;
          -  Clinically relevant abnormalities on a 12-lead ECG, except for abnormalities related&#xD;
             to hepatic impairment, after 5 minutes in the supine position at screening and on Day&#xD;
             1 pre-dose.&#xD;
&#xD;
        Additional exclusion criteria for healthy participants (Group 3)&#xD;
&#xD;
          -  History or clinical evidence of any disease and/or existence of any surgical or&#xD;
             medical condition (e.g., cholecystectomy), which might interfere with the ADME of the&#xD;
             study treatment (except for appendectomy and herniotomy).&#xD;
&#xD;
          -  History or clinical evidence of alcohol or drug abuse within the 3 years prior to&#xD;
             screening.&#xD;
&#xD;
          -  Family or personal history of prolonged bleeding or bleeding disorders, intracranial&#xD;
             vascular diseases, stroke, reasonable suspicion of vascular malformations, or peptic&#xD;
             ulcers.&#xD;
&#xD;
          -  Previous treatment with any prescribed medications or over-the-counter medications&#xD;
             within 2 weeks or 5 times the terminal half-life (t½), whichever is longer prior to&#xD;
             study treatment administration (excludes contraceptives and hormone replacement&#xD;
             therapy).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Idorsia Pharmaceuticals Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CRS Clinical Research Services</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>November 15, 2022</last_update_submitted>
  <last_update_submitted_qc>November 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04406896
org study id: ID-076-108
secondary id: 2020-001315-25
nct id: NCT04406896
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a prospective, single-center, open-label, single-dose, Phase 1 study, to assess the
      effect of mild and moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics
      of selatogrel (ACT-246475).
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Moderate hepatic impaired participants will be dosed after an interim analysis of at least 6 participants with mild hepatic impairment. Healthy participants will be matched to hepatic impaired participants.
primary purpose: Other
masking: None (Open Label)
measure: The maximum plasma concentration (Cmax) of selatogrel
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
measure: Time to reach Cmax (tmax)
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
measure: Area under the plasma concentration-time curves (AUC0-t) of selatogrel
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
measure: The area under the plasma concentration-time curve from zero to infinity (AUC0-inf) of selatogrel
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
measure: Terminal half-life (t½) of selatogrel
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
measure: The apparent clearance (CL/F) of selatogrel
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
measure: The apparent volume of distribution (Vz/F) of selatogrel
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
measure: Plasma protein binding of selatogrel
time frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose and post-dose).
measure: Change from baseline in supine blood pressure
time frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3.
measure: Change from baseline in temperature
time frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3.
measure: Change from baseline in pulse rate
time frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3.
measure: Change from baseline in body weight
time frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3.
measure: Change from baseline in clinical laboratory tests
time frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3.
measure: Change from baseline at each time point of measurement in ECG variables.
time frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3.
measure: Inhibition of platelet aggregation
time frame: Multiple predefined times on Day 1 (pre-dose) up to Day 3.
arm group label: Participants with mild hepatic impairment (Group 1)
arm group type: Experimental
description: Participant with Child-Pugh Grade A Score of 5-6.
arm group label: Participants with moderate hepatic impairment (Group 2)
arm group type: Experimental
description: Participant with moderate hepatic impairment with a Child-Pugh Grade B Score of 7-9.
arm group label: Healthy participants (Group 3)
arm group type: Experimental
intervention type: Drug
intervention name: Selatogrel
description: A single subcutaneous injection of 16 mg.
arm group label: Healthy participants (Group 3)
arm group label: Participants with mild hepatic impairment (Group 1)
arm group label: Participants with moderate hepatic impairment (Group 2)
other name: ACT-246475
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Idorsia Pharmaceuticals Ltd.
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Liver Diseases
sharing ipd: No