<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/NCT02998437</url>
  </required_header>
  <id_info>
    <org_study_id>IY81149-DI03</org_study_id>
    <nct_id>NCT02998437</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Pharmacokinetic Drug Interactions and Safety of Clarithromycin, Amoxicillin and Ilaprazole</brief_title>
  <acronym>DDI</acronym>
  <official_title>A Randomized, Open-label, Parallel-design Study to Evaluate Pharmacokinetic Drug Interactions and Safety After Coadministration of Clarithromycin, Amoxicillin and Ilaprazole</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Il-Yang Pharm. Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Il-Yang Pharm. Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluate the pharmacokinetic drug interaction in Ilaprazole, Clarithromycin,&#xD;
      Amoxicillin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study evaluate the pharmacokinetic drug interaction and safety in Ilaprazole,&#xD;
      Clarithromycin, Amoxicillin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ilaprazole AUClast(Area Under the plasma concentration-time Curve at the last observed time point)</measure>
    <time_frame>Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ilaprazole Cmax(the maximum serum concentration)</measure>
    <time_frame>Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Clarithromycin, Amoxicillin AUClast</measure>
    <time_frame>Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Clarithromycin, Amoxicillin Cmax</measure>
    <time_frame>Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ilaprazole AUCinf(Area Under the plasma concentration-time Curve from time zero to infinity)</measure>
    <time_frame>Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ilaprazole Tmax(the time to reach Cmax)</measure>
    <time_frame>Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ilaprazole t1/2(the elimination half-life)</measure>
    <time_frame>Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ilaprazole CL/F(the oral clearance)</measure>
    <time_frame>Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ilaprazole Vd/F(apparent volume of distribution after non-intravenous administration)</measure>
    <time_frame>Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clarithromycin, Amoxicillin AUCinf</measure>
    <time_frame>Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clarithromycin, Amoxicillin Tmax</measure>
    <time_frame>Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clarithromycin, Amoxicillin t1/2</measure>
    <time_frame>Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clarithromycin, Amoxicillin CL/F</measure>
    <time_frame>Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clarithromycin, Amoxicillin Vd/F</measure>
    <time_frame>Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Drug Interaction Potentiation</condition>
  <arm_group>
    <arm_group_label>Ilaprazole 10mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Period 1: Ilaprazole 10mg 1 tab.m one a day&#xD;
Period 2: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap. twice a day, 6 days Ilaprazole 10mg, one a day at the 5 day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clarithromycin 500mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Period 1: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day&#xD;
Period 2: Ilaprazole 10mg 1 tab., twice a day, 6 days Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day at the 5 day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amoxicillin 500mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Period 1: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day&#xD;
Period 2: Ilaprazole 10mg 1 tab., twice a day, 6 days Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day at 5 day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ilaprazole 10mg</intervention_name>
    <description>Period 1: Ilaprazole 10mg, one a day, one day Period 2: Ilaprazole 10mg, twice a day, 6 days</description>
    <arm_group_label>Ilaprazole 10mg</arm_group_label>
    <other_name>Noltec(the brand name)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clarithromycin 500mg</intervention_name>
    <description>Period 1: Clarithromycin 500mg 1 tab., twice a day, one day Period 2: Clarithromycin 500mg 1 tab., one a day at 5 day</description>
    <arm_group_label>Clarithromycin 500mg</arm_group_label>
    <other_name>Klaricid 500mg(the brand name)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin 500 Mg</intervention_name>
    <description>Period 1: Amoxicillin 500mg 2 cap., one a day, one day Period 2: Amoxicillin 500mg 2 cap., one a day at 5 day</description>
    <arm_group_label>Amoxicillin 500mg</arm_group_label>
    <other_name>Amoxicillin Cap. 500mg Chongkundang(the brand name)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male adults aged ≥19 years and &lt;50 years at screening&#xD;
&#xD;
          2. Body mass index ≥18.5 and &lt;25&#xD;
&#xD;
               -  Body mass index (kg/m2) = body weight (kg)/[height (m)]2&#xD;
&#xD;
          3. Men who have sexual relationship with women of child bearing potential must give&#xD;
             consent to using contraceptive measures (condoms, spermicide, and menstrual cycle&#xD;
             control) and avoiding sperm donation during the study and up to 28 days following the&#xD;
             last dose of IMP (these contraceptive measures are not required if the male subject or&#xD;
             female partner is infertile).&#xD;
&#xD;
          4. Those who voluntarily decided to participate in this study and gave written consent to&#xD;
             comply with the requirements after receiving sufficient explanation and fully&#xD;
             understanding this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity or history of clinically significant hypersensitivity to active&#xD;
             ingredients or excipients (in particular, Yellow No. 4 (Tartrazine); Yellow No. 5&#xD;
             (Sunset Yellow FCF); macrolide antibiotics such as Clarithromycin and erythromycin; or&#xD;
             Penicillins)&#xD;
&#xD;
          2. History of QT prolongation or ventricular arrhythmia (including Torsadedes de pointes)&#xD;
&#xD;
          3. Clinically significant, current or past disorder of hepatobiliary (severe hepatic&#xD;
             impairment, etc.), renal (severe renal impairment, etc.), nervous, immune,&#xD;
             respiratory, endocrine, blood•tumor, cardiovascular (heart failure, etc.), or&#xD;
             psychiatric system&#xD;
&#xD;
          4. History of gastrointestinal disorder (Crohn's disease, ulcer, etc.) or operation&#xD;
             (excluding simple appendectomy or herniotomy) that may affect drug absorption&#xD;
&#xD;
          5. Administration of other IMP from other study (including biological comparability test)&#xD;
             within 3 months of the first dose of IMP.&#xD;
&#xD;
          6. Whole blood donation within 60 days, or apheresis donation within 30 days before the&#xD;
             first dose of IMP.&#xD;
&#xD;
          7. Constant caffeine intake (&gt; 5 cups of coffee/day, &gt; 1250 cc of tea/day, &gt; 1250 cc of&#xD;
             cola/day), constant smoking (more than 10 cigarettes/day) or constant alcohol drinking&#xD;
             (more than 210 g/week) or inability to refrain from alcohol consumption from 2 days&#xD;
             before the first dose of IMP until the end of PK assessment.&#xD;
&#xD;
          8. Consumption of grapefruit-containing food within 7 days before the first dose of IMP&#xD;
&#xD;
          9. History of drug abuse within 1 year before screening, or positive response in urine&#xD;
             drug misuse/abuse screening test&#xD;
&#xD;
         10. Use of medicinal products that are expected to or may affect the metabolism of IMP;&#xD;
             St. John's wort; or relevant preparations within 30 days of IMP administration&#xD;
&#xD;
         11. Use of following medicinal products within given time period excluding local&#xD;
             preparations, which do not have significant systemic absorption, and hormonal&#xD;
             contraceptives&#xD;
&#xD;
               -  Prescription drug within 14 days of the first dose of IMP&#xD;
&#xD;
               -  OTC including health supplements and vitamins within 7 days of the first dose of&#xD;
                  IMP&#xD;
&#xD;
               -  Medicinal products via depot injection or other implantations within 30 days of&#xD;
                  the first dose of IMP (excluding contraceptives)&#xD;
&#xD;
               -  Drug metabolizing enzyme inducer or inhibitor such as barbiturate within 30 days&#xD;
                  before the first dose of IMP&#xD;
&#xD;
         12. Stable vital sign measured in sitting position at screening: systolic blood pressure &gt;&#xD;
             150 mmHg or &lt; 90 mmHg, diastolic blood pressure &gt; 100 mmHg or &lt; 50 mmHg, pulse rate &gt;&#xD;
             110 bpm or &lt;40 bpm&#xD;
&#xD;
         13. Following findings at screening&#xD;
&#xD;
               -  Blood total bilirubin &gt; 1.5 x upper limit of normal&#xD;
&#xD;
               -  Blood AST (SGOT), ALT (SGPT) &gt; 1.25 x upper limit of normal&#xD;
&#xD;
               -  MDRD-estimated eGFR &lt; 60 mL/min/1.73m2 eGFR (estimated glomerular filtration&#xD;
                  rate)(mL/min/1.73m2) = 175 x [serum creatinine (mg/dL)]-1.154 x [age&#xD;
                  (years)]-0.203&#xD;
&#xD;
               -  Positive serum test (hepatitis B, hepatitis C, HIV, syphilis)&#xD;
&#xD;
         14. Those considered ineligible by the investigator due to other screening results or&#xD;
             reasons.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Min MS Park, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Severance Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2017</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>Amoxicillin</mesh_term>
    <mesh_term>Clarithromycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</ipd_description>
  </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/NCT02998437
org study id: IY81149-DI03
nct id: NCT02998437
lead sponsor: 
collaborator: 
has dmc: Yes
This study evaluate the pharmacokinetic drug interaction in Ilaprazole, Clarithromycin,
      Amoxicillin.
This study evaluate the pharmacokinetic drug interaction and safety in Ilaprazole,
      Clarithromycin, Amoxicillin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ilaprazole AUClast(Area Under the plasma concentration-time Curve at the last observed time point)
time frame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole Cmax(the maximum serum concentration)
time frame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin AUClast
time frame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin Cmax
time frame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Ilaprazole AUCinf(Area Under the plasma concentration-time Curve from time zero to infinity)
time frame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole Tmax(the time to reach Cmax)
time frame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole t1/2(the elimination half-life)
time frame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole CL/F(the oral clearance)
time frame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole Vd/F(apparent volume of distribution after non-intravenous administration)
time frame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin AUCinf
time frame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin Tmax
time frame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin t1/2
time frame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin CL/F
time frame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin Vd/F
time frame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
arm group label: Ilaprazole 10mg
arm group type: Experimental
description: Period 1: Ilaprazole 10mg 1 tab.m one a day
Period 2: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap. twice a day, 6 days Ilaprazole 10mg, one a day at the 5 day
arm group label: Clarithromycin 500mg
arm group type: Active Comparator
description: Period 1: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day
Period 2: Ilaprazole 10mg 1 tab., twice a day, 6 days Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day at the 5 day
arm group label: Amoxicillin 500mg
arm group type: Active Comparator
description: Period 1: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day
Period 2: Ilaprazole 10mg 1 tab., twice a day, 6 days Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day at 5 day
intervention type: Drug
intervention name: Ilaprazole 10mg
description: Period 1: Ilaprazole 10mg, one a day, one day Period 2: Ilaprazole 10mg, twice a day, 6 days
arm group label: Ilaprazole 10mg
other name: Noltec(the brand name)
intervention type: Drug
intervention name: Clarithromycin 500mg
description: Period 1: Clarithromycin 500mg 1 tab., twice a day, one day Period 2: Clarithromycin 500mg 1 tab., one a day at 5 day
arm group label: Clarithromycin 500mg
other name: Klaricid 500mg(the brand name)
intervention type: Drug
intervention name: Amoxicillin 500 Mg
description: Period 1: Amoxicillin 500mg 2 cap., one a day, one day Period 2: Amoxicillin 500mg 2 cap., one a day at 5 day
arm group label: Amoxicillin 500mg
other name: Amoxicillin Cap. 500mg Chongkundang(the brand name)
criteria: 
gender: Male
minimum age: 19 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Min MS Park, PhD
role: Principal Investigator
affiliation: Severance Hospital
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Amoxicillin
mesh term: Clarithromycin
sharing ipd: Undecided
ipd description: Undecided