<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/NCT03814200</url>
  </required_header>
  <id_info>
    <org_study_id>ID-076-106</org_study_id>
    <secondary_id>2018-004226-28</secondary_id>
    <nct_id>NCT03814200</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Effect of Rifampicin on the Uptake and Breakdown of ACT-246475 in Healthy Subjects</brief_title>
  <official_title>A Single-center, Randomized, Double-blind, Two-period Cross-over Study to Investigate the Effect of a Single Intravenous Dose of Rifampicin on the Pharmacokinetics of ACT-246475 in 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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will investigate the effect of rifampicin on the uptake and breakdown of ACT-246475&#xD;
      in healthy subjects&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2019</start_date>
  <completion_date type="Actual">February 19, 2019</completion_date>
  <primary_completion_date type="Actual">February 12, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve (AUC) from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t)</measure>
    <time_frame>Up to 36 hours after treatment administration</time_frame>
    <description>The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC from zero to infinity (AUC0-inf)</measure>
    <time_frame>Up to 36 hours after treatment administration</time_frame>
    <description>The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The maximum plasma concentration (Cmax)</measure>
    <time_frame>Up to 36 hours after treatment administration</time_frame>
    <description>The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The time to reach Cmax (tmax)</measure>
    <time_frame>Up to 36 hours after treatment administration</time_frame>
    <description>The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal half-life (t½)</measure>
    <time_frame>Up to 36 hours after treatment administration</time_frame>
    <description>The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Healthy Subject</condition>
  <arm_group>
    <arm_group_label>Treatment period A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A1: saline 0.9%&#xD;
followed by&#xD;
Treatment A2: ACT-246475</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment period B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment B1: rifampicin&#xD;
followed by&#xD;
Treatment B2: ACT-246475</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Single i.v. infusion of 100 mL saline 0.9% for 30 min</description>
    <arm_group_label>Treatment period A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACT-246475</intervention_name>
    <description>Single s.c. dose of 4 mg ACT-246475 in the thigh under fasting conditions</description>
    <arm_group_label>Treatment period A</arm_group_label>
    <arm_group_label>Treatment period B</arm_group_label>
    <other_name>Selatogrel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifampicin</intervention_name>
    <description>Single i.v. infusion of 600 mg rifampicin (100 mL) for 30 min</description>
    <arm_group_label>Treatment period B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent in a language understandable to the subject prior to any&#xD;
             study-mandated procedure&#xD;
&#xD;
          -  Healthy male and female subjects aged between 18 and 65 years (inclusive) at Screening&#xD;
&#xD;
          -  Body mass index of 18.0 to 30.0 kg/m2 (inclusive) at Screening&#xD;
&#xD;
          -  Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse&#xD;
             rate 45-90 bpm (inclusive), measured on the same arm, after 5 min in the supine&#xD;
             position at screening and on Day -1 of the first period&#xD;
&#xD;
          -  Hematology and coagulation test results not deviating from the normal range to a&#xD;
             clinically relevant extent at Screening and on Day -1 of the first period&#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 of the first treatment period and must&#xD;
             agree to consistently and correctly use a highly effective method of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous exposure to ACT-246475.&#xD;
&#xD;
          -  Previous exposure to rifampicin within 3 months prior to Screening.&#xD;
&#xD;
          -  Known hypersensitivity to P2Y12 receptor antagonists or rifampicin, or to any of the&#xD;
             rifamycins, or any of their excipients&#xD;
&#xD;
          -  Loss of 250 mL or more of blood 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;
&#xD;
          -  Family or personal history of prolonged bleeding (e.g., after surgical intervention)&#xD;
             or bleeding disorders (e.g., thrombocytopenia, clotting disturbances), intracranial&#xD;
             vascular diseases, stroke, reasonable suspicion of vascular malformations, or peptic&#xD;
             ulcers&#xD;
&#xD;
          -  Known platelet disorders (e.g., Glanzmann thromboasthenia, von Willebrand disease,&#xD;
             platelet release defect)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>QPS Netherlands B.V.</name>
      <address>
        <city>Groningen</city>
        <zip>9700</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <results_reference>
    <citation>Schilling U, Dingemanse J, Voors-Pette C, Romeijn C, Dogterom P, Ufer M. Effect of Rifampin-Mediated OATP1B1 and OATP1B3 Transporter Inhibition on the Pharmacokinetics of the P2Y12 Receptor Antagonist Selatogrel. Clin Transl Sci. 2020 Sep;13(5):886-890. doi: 10.1111/cts.12774. Epub 2020 Mar 31.</citation>
    <PMID>32166864</PMID>
  </results_reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rifampin</mesh_term>
  </intervention_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/NCT03814200
org study id: ID-076-106
secondary id: 2018-004226-28
nct id: NCT03814200
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study will investigate the effect of rifampicin on the uptake and breakdown of ACT-246475
      in healthy subjects
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Area under the plasma concentration-time curve (AUC) from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t)
time frame: Up to 36 hours after treatment administration
description: The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: AUC from zero to infinity (AUC0-inf)
time frame: Up to 36 hours after treatment administration
description: The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: The maximum plasma concentration (Cmax)
time frame: Up to 36 hours after treatment administration
description: The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: The time to reach Cmax (tmax)
time frame: Up to 36 hours after treatment administration
description: The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
measure: Terminal half-life (t½)
time frame: Up to 36 hours after treatment administration
description: The plasma PK parameters of ACT-246475 will be derived by non-compartmental analysis of the plasma concentration-time profiles
arm group label: Treatment period A
arm group type: Experimental
description: Treatment A1: saline 0.9%
followed by
Treatment A2: ACT-246475
arm group label: Treatment period B
arm group type: Experimental
description: Treatment B1: rifampicin
followed by
Treatment B2: ACT-246475
intervention type: Drug
intervention name: Saline
description: Single i.v. infusion of 100 mL saline 0.9% for 30 min
arm group label: Treatment period A
intervention type: Drug
intervention name: ACT-246475
description: Single s.c. dose of 4 mg ACT-246475 in the thigh under fasting conditions
arm group label: Treatment period A
arm group label: Treatment period B
other name: Selatogrel
intervention type: Drug
intervention name: Rifampicin
description: Single i.v. infusion of 600 mg rifampicin (100 mL) for 30 min
arm group label: Treatment period B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Netherlands
citation: Schilling U, Dingemanse J, Voors-Pette C, Romeijn C, Dogterom P, Ufer M. Effect of Rifampin-Mediated OATP1B1 and OATP1B3 Transporter Inhibition on the Pharmacokinetics of the P2Y12 Receptor Antagonist Selatogrel. Clin Transl Sci. 2020 Sep;13(5):886-890. doi: 10.1111/cts.12774. Epub 2020 Mar 31.
PMID: 32166864
responsible party type: Sponsor
mesh term: Rifampin
sharing ipd: No