<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/NCT02229877</url>
  </required_header>
  <id_info>
    <org_study_id>7264-011</org_study_id>
    <secondary_id>AF219-011</secondary_id>
    <nct_id>NCT02229877</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Effect of Intragastric pH and Fasting on the Pharmacokinetics of Gefapixant (AF-219/MK-7264)</brief_title>
  <official_title>A Study in Healthy Subjects to Assess the Effect of Intragastric pH and Fasting on the Multiple-Dose Pharmacokinetics of AF-219</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Afferent Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celerion</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Afferent Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to: determine the effect of stomach pH on the multiple dose&#xD;
      pharmacokinetics (PK) of gefapixant (AF-219); assess the effect of multiple doses of&#xD;
      gefapixant on various sensory assessments; and, assess the safety and tolerability of&#xD;
      gefapixant.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 6, 2014</start_date>
  <completion_date type="Actual">May 22, 2015</completion_date>
  <primary_completion_date type="Actual">May 14, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of Intragastric pH on gefapixant PK</measure>
    <time_frame>At pre-dose (time 0) and at 1, 2, 3, 5, 8, and 12 hours post dose</time_frame>
    <description>Analysis of variance (ANOVA) will be performed on log normal-transformed Cmax and AUC0-t values to determine the extent of a drug interaction, if any, of omeprazole on the plasma gefapixant PK parameters. These analyses will be conducted for both fed and fasted conditions and the 50 mg and 150 mg treatments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of Fasting on gefapixant PK</measure>
    <time_frame>At pre-dose (time 0) and at 1, 2, 3, 5, 8, and 12 hours post dose</time_frame>
    <description>ANOVA will be performed on log normal-transformed Cmax and AUC0-t values to determine if fasting affects plasma gefapixant PK parameters.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Gefapixant + Omeprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gefapixant oral tablets (25mg, 50 mg, 150 mg) administered twice daily for 18 days&#xD;
+ Omeprazole oral capsules (40 mg) administered twice daily for 8.5 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole</intervention_name>
    <description>40 mg oral capsules administered twice daily for 8.5 days</description>
    <arm_group_label>Gefapixant + Omeprazole</arm_group_label>
    <other_name>Prilosec</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gefapixant</intervention_name>
    <description>Gefapixant oral tablet (25 mg administered as a divided 50 mg tablet) administered twice daily for 2 days</description>
    <arm_group_label>Gefapixant + Omeprazole</arm_group_label>
    <other_name>AF-219</other_name>
    <other_name>MK-7264</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gefapixant</intervention_name>
    <description>Gefapixant oral tablet (50 mg tablet) administered twice daily for 8 days</description>
    <arm_group_label>Gefapixant + Omeprazole</arm_group_label>
    <other_name>AF-219</other_name>
    <other_name>MK-7264</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gefapixant</intervention_name>
    <description>Gefapixant oral tablet (150 mg administered as three 50 mg tablets) administered twice daily for 8 days</description>
    <arm_group_label>Gefapixant + Omeprazole</arm_group_label>
    <other_name>AF-219</other_name>
    <other_name>MK-7264</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Must be informed of the nature of the study and have provided written informed voluntary&#xD;
        consent;&#xD;
&#xD;
        Able to speak, read, and understand English;&#xD;
&#xD;
        Healthy males or females, of any race, between 18 and 55 years of age, inclusive;&#xD;
&#xD;
        Body mass index (BMI) &gt;18.5 and &lt;32.0 kg/m2 and weigh 50 - 100 kg;&#xD;
&#xD;
        In good general health ;&#xD;
&#xD;
        Non-smokers for at least 5 years;&#xD;
&#xD;
        If a female of child-bearing potential (i.e., have not undergone a hysterectomy or&#xD;
        bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12&#xD;
        months), agree to use 2 forms of acceptable birth control; or if a male, they and/or their&#xD;
        partner of child-bearing potential agree to use 2 forms of acceptable birth control;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Any disease or condition that might affect drug absorption, metabolism, or excretion or&#xD;
        clinically significant cardiovascular, hematological, renal, hepatic, pulmonary, endocrine,&#xD;
        gastrointestinal, immunological, dermatological, neurological, or psychiatric disease;&#xD;
&#xD;
        Clinically significant illness or clinically significant surgery within 4 weeks before the&#xD;
        administration of study medication;&#xD;
&#xD;
        Any past sinus surgery, upper respiratory tract infection within 2 weeks before dosing, or&#xD;
        history of hay fever during the time of the year that dosing will be taking place;&#xD;
&#xD;
        History of GERD, heartburn, or nausea more than once a month, or any similar symptoms&#xD;
        requiring the regular use of antacids, or any use of H2 histamine blockers or proton pump&#xD;
        inhibitors within 12 months of Screening;&#xD;
&#xD;
        Have a positive screening test for Helicobacter pylori;&#xD;
&#xD;
        QTcB &gt;450 msec in males or &gt;460 msec in females;&#xD;
&#xD;
        Known or suspected hypersensitivity or allergic reaction to any of the components of&#xD;
        gefapixant or omeprazole capsules;&#xD;
&#xD;
        If female, is pregnant or breast feeding, or has a positive pregnancy test pre dose;&#xD;
&#xD;
        Blood loss or blood donation of &gt;550 mL within 90 days or plasma donation &gt;500 mL within 14&#xD;
        days before administration of the first dose of study drug;&#xD;
&#xD;
        Chronic use of any systemic medications; use of a drug therapy known to induce or inhibit&#xD;
        hepatic drug metabolism within 30 days before the first dose of study medication; or use of&#xD;
        any medications including antacids, high dose multivitamins, nutritional supplements, and&#xD;
        herbal preparations, within 14 days before the first dose of study drug;&#xD;
&#xD;
        Past or current history or evidence of drug or alcohol abuse, use of any recreational soft&#xD;
        drugs (e.g., marijuana) within 3 months of screening, use of any hard drugs (such as&#xD;
        cocaine, phencyclidine (PCP), and crack) within 1 year of screening, and/or a positive&#xD;
        screen for substances of abuse or alcohol at screening or pre dose;&#xD;
&#xD;
        Ingestion of grapefruit or grapefruit juice within 48 hours before dose administration;&#xD;
&#xD;
        Positive urine cotinine test at Screening or Day 1 pre dose;&#xD;
&#xD;
        Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human&#xD;
        immunodeficiency virus (HIV) antibody;&#xD;
&#xD;
        Receipt of an investigational product or device, or participation in a drug research study&#xD;
        within a period of 30 days (or 5 half lives of the drug, whichever is longer) before the&#xD;
        first dose of study medication;&#xD;
&#xD;
        Receipt of an investigational immunomodulator or monoclonal antibody within 180 days (or 5&#xD;
        half lives, whichever is longer) before the first dose of study medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Terry O'Reilly, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Celerion</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <results_reference>
    <citation>Gupta P, Hussain A, Ford AP, Smith S, Nussbaum JC, Stoch A, Iwamoto M. Clinical Formulation Bridging of Gefapixant, a P2X3-Receptor Antagonist, for the Treatment of Chronic Cough. Clin Pharmacol Drug Dev. 2022 Sep;11(9):1054-1067. doi: 10.1002/cpdd.1105. Epub 2022 May 5.</citation>
    <PMID>35510785</PMID>
  </results_reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>July 20, 2022</last_update_submitted>
  <last_update_submitted_qc>July 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 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>Omeprazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </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/NCT02229877
org study id: 7264-011
secondary id: AF219-011
nct id: NCT02229877
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to: determine the effect of stomach pH on the multiple dose
      pharmacokinetics (PK) of gefapixant (AF-219); assess the effect of multiple doses of
      gefapixant on various sensory assessments; and, assess the safety and tolerability of
      gefapixant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Effect of Intragastric pH on gefapixant PK
time frame: At pre-dose (time 0) and at 1, 2, 3, 5, 8, and 12 hours post dose
description: Analysis of variance (ANOVA) will be performed on log normal-transformed Cmax and AUC0-t values to determine the extent of a drug interaction, if any, of omeprazole on the plasma gefapixant PK parameters. These analyses will be conducted for both fed and fasted conditions and the 50 mg and 150 mg treatments.
measure: Effect of Fasting on gefapixant PK
time frame: At pre-dose (time 0) and at 1, 2, 3, 5, 8, and 12 hours post dose
description: ANOVA will be performed on log normal-transformed Cmax and AUC0-t values to determine if fasting affects plasma gefapixant PK parameters.
arm group label: Gefapixant + Omeprazole
arm group type: Experimental
description: Gefapixant oral tablets (25mg, 50 mg, 150 mg) administered twice daily for 18 days
+ Omeprazole oral capsules (40 mg) administered twice daily for 8.5 days
intervention type: Drug
intervention name: Omeprazole
description: 40 mg oral capsules administered twice daily for 8.5 days
arm group label: Gefapixant + Omeprazole
other name: Prilosec
intervention type: Drug
intervention name: Gefapixant
description: Gefapixant oral tablet (25 mg administered as a divided 50 mg tablet) administered twice daily for 2 days
arm group label: Gefapixant + Omeprazole
other name: AF-219
other name: MK-7264
intervention type: Drug
intervention name: Gefapixant
description: Gefapixant oral tablet (50 mg tablet) administered twice daily for 8 days
arm group label: Gefapixant + Omeprazole
other name: AF-219
other name: MK-7264
intervention type: Drug
intervention name: Gefapixant
description: Gefapixant oral tablet (150 mg administered as three 50 mg tablets) administered twice daily for 8 days
arm group label: Gefapixant + Omeprazole
other name: AF-219
other name: MK-7264
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Terry O'Reilly, M.D.
role: Principal Investigator
affiliation: Celerion
country: United States
citation: Gupta P, Hussain A, Ford AP, Smith S, Nussbaum JC, Stoch A, Iwamoto M. Clinical Formulation Bridging of Gefapixant, a P2X3-Receptor Antagonist, for the Treatment of Chronic Cough. Clin Pharmacol Drug Dev. 2022 Sep;11(9):1054-1067. doi: 10.1002/cpdd.1105. Epub 2022 May 5.
PMID: 35510785
responsible party type: Sponsor
mesh term: Omeprazole
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php