<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/NCT04444011</url>
  </required_header>
  <id_info>
    <org_study_id>3571-DDI-1006</org_study_id>
    <nct_id>NCT04444011</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Interactions of Quadruple Therapy With Anaprazole/Amoxicilin/Clarithromycin/Bismuth</brief_title>
  <official_title>A Single-center, Randomized, Open-label, Crossover Study to Evaluate the Pharmacokinetic Drug-drug Interaction of the Quadruple Therapy With Anaprazole/Amoxicilin/Clarithromycin/Bismuth in Healthy Chinese Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sihuan Pharmaceutical Holdings Group Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sihuan Pharmaceutical Holdings Group Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A single-center, randomized, open-label, crossover study to evaluate the pharmacokinetic&#xD;
      drug-drug interaction and safety of the quadruple therapy with Anaprazole 20mg/Amoxicilin&#xD;
      1000mg/Clarithromycin 500mg/Bismuth Potassium Citrate 0.6g in healthy Chinese male subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study composed of 2 cohorts, using a 4*4 or 2*2 crossover design in cohort 1 and 2,&#xD;
      respectively. 4 rotating treatment sequences in cohort 1, each treatment sequence comprised 4&#xD;
      treatment periods, separated by a washout period of 9 days; 2 rotating treatment sequences in&#xD;
      cohort 2, each treatment sequence comprised 2 treatment periods, separated by a washout&#xD;
      period of 9 days&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">October 15, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2020</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cohort 1: Css,max of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)</measure>
    <time_frame>Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 5，Day 19，Day 33，Day 47</time_frame>
    <description>Css,max is the peak plasma concentration at steady state</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 1: AUC of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)</measure>
    <time_frame>Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 5，Day 19，Day 33，Day 47</time_frame>
    <description>AUC is area under the plasma concentration-time curve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2: Cmax of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)</measure>
    <time_frame>Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 1，Day 11</time_frame>
    <description>Cmax is the peak plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 2: AUC of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)</measure>
    <time_frame>Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 1，Day 11</time_frame>
    <description>AUC is area under the plasma concentration-time curve</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events and serious adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>From signing informed consent to study completion. 56 days minimum, 68 days maximum(Cohort 1); 30 days minimum, 32 days maximum(Cohort 2)</time_frame>
    <description>All adverse events will be monitored in each subject</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">32</enrollment>
  <condition>Healthy Male Volunteers</condition>
  <arm_group>
    <arm_group_label>Anaprazole Sodium enteric-coated tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods of cohort 1 ( only once on the morning of D5 of treatment periods), one tablet each time.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amoxicillin capsules</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>&quot;Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods of cohort 1 ( only once on the morning of D5 of treatment periods), 2 capsules each time.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clarithromycin tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>&quot;Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods of cohort 1 ( only once on the morning of D5 of treatment periods), 2 tablets each time.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>&quot;Cohort 1: Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods ( only once on the morning of D5 of treatment periods).&#xD;
Cohort 2: Administered orally on an empty stomach once on the morning of D1 of treatment periods</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin+Bismuth</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administered orally on an empty stomach once on the morning of D1 of treatment periods in cohort 2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anaprazole Sodium</intervention_name>
    <description>Anaprazole Sodium isthePPI inhibitor</description>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin</arm_group_label>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin+Bismuth</arm_group_label>
    <arm_group_label>Anaprazole Sodium enteric-coated tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin</intervention_name>
    <description>antibiotic</description>
    <arm_group_label>Amoxicillin capsules</arm_group_label>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin</arm_group_label>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin+Bismuth</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clarithromycin</intervention_name>
    <description>antibiotic</description>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin</arm_group_label>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin+Bismuth</arm_group_label>
    <arm_group_label>Clarithromycin tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bismuth</intervention_name>
    <description>Bismuth is to protect the gastric mucosa</description>
    <arm_group_label>Anaprazole + Amoxicillin +Clarithromycin+Bismuth</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1.The subject is capable of understanding and complying with protocol requirements,&#xD;
             and signed and dated a written informed consent form voluntarily&#xD;
&#xD;
          -  2.The subject is a Chinese adult male, aged 18 to 35 years, inclusive.&#xD;
&#xD;
          -  3.The subject is a H. pylori-negative via UBT.&#xD;
&#xD;
          -  4.The subject weighed at least 50.0 kg and had a body mass index (BMI) between 19.0&#xD;
             kg/m^2 and 26.0 kg/m^2, inclusive.&#xD;
&#xD;
          -  5.Has clinical laboratory evaluations, vital signs and ECG testing within the&#xD;
             reference range, and medical history and physicial examination results are normal.&#xD;
             Participants with evaluations outside the reference range that are deemed not&#xD;
             clinically significant by the investigator may be included at investigator discretion&#xD;
&#xD;
          -  6.The subject with a female partner of childbearing potential agrees to use adequate&#xD;
             contraception from signing of informed consent throughout the duration of the study&#xD;
             and for 3 months after last dose.&#xD;
&#xD;
          -  7.The subjects have a good lifestyle and can keep good communication with the&#xD;
             investigators and comply with the requirements of clinical trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1.Has clinical significant drug allergy or allergic disease history(Such as asthma,&#xD;
             urticaria, eczema dermatitis, etc), or has hypersensitivity or allergy to&#xD;
             investigatory drugs or related supplements；&#xD;
&#xD;
          -  2.Has clinical significant ECG abnormal history or family history of long QT&#xD;
             syndrome(Grandparents, parents and siblings)&#xD;
&#xD;
          -  3.Any disease or medical history that may significantly affect the absorption,&#xD;
             distribution, metabolism, and excretion of drugs, or any condition that may pose a&#xD;
             hazard to the subject. Such as:&#xD;
&#xD;
               -  Inflammatory bowel disease, gastric ulcer, duodenal ulcer, gastrointestinal /&#xD;
                  rectal bleeding, persistent nausea, or other clinically significant&#xD;
                  gastrointestinal abnormalities;&#xD;
&#xD;
               -  Has suffered from gastrointestinal diseases or complications that may affect the&#xD;
                  absorption of drugs (ie: malabsorption, gastroesophageal reflux, peptic ulcer,&#xD;
                  erosive esophagitis, frequent heartburn) within 6 months before screening or had&#xD;
                  history of gastrointestinal surgery (for example: gastrectomy, gastrointestinal&#xD;
                  anastomosis, intestinal resection, gastric bypass, gastric segmentation or&#xD;
                  gastric banding, cholecystectomy, except for appendicitis surgery and&#xD;
                  proctectomy);&#xD;
&#xD;
               -  Evidence of liver disease or clinically impaired liver function at the time of&#xD;
                  screening (eg AST, ALT or total bilirubin&gt; 1.5 times ULN);&#xD;
&#xD;
               -  A history or evidence of nephropathy or renal insufficiency at the time of&#xD;
                  screening, showing clinically significant abnormality of creatinine or abnormal&#xD;
                  urine composition (such as proteinuria, creatinine&gt; 176.8 umol / L, etc.)&#xD;
&#xD;
               -  Has difficulty swallowing oral preparations.&#xD;
&#xD;
          -  4.Thyroid stimulating hormone (TSH)&gt; ULN; or serum free triiodothyronine (FT3)&gt; ULN;&#xD;
             or serum free thyroxine (FT4)&gt; ULN at the time of screening;&#xD;
&#xD;
          -  5. Frequent smokers and alcoholics within 3 months before screening (smoke more than 5&#xD;
             cigarettes / day, drink more than 21 units of alcohol per week, 1 unit = 360 mL beer&#xD;
             or 45 mL liquor or 150 mL wine), or can't stop using any tobacco products, and alcohol&#xD;
             intake during the study period ; or those who have a positive alcohol breath test&#xD;
             before enrollment;&#xD;
&#xD;
          -  6. Has received any investigational compound (including post-marketing investigational&#xD;
             drugs) or participated in clinical trials of any drugs /devices within 3 months before&#xD;
             screening;&#xD;
&#xD;
          -  7. A history of drug abuse within 12 months before screening or a positive urine test&#xD;
             result at screening;&#xD;
&#xD;
          -  8. Has used any prescription drugs, non-prescription drugs (including chemical drugs,&#xD;
             vitamin drugs, Chinese herbal medicines, etc.) within 4 weeks before administration of&#xD;
             investigational drugs;&#xD;
&#xD;
          -  9. Has taken foods that affect CYP3A4 (such as grapefruit or beverages containing&#xD;
             grapefruit) within 2 weeks before administration of investigational drugs;&#xD;
&#xD;
          -  10. Human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C&#xD;
             antibody, and Treponema pallidum specific antibody test results were positive at&#xD;
             screening;&#xD;
&#xD;
          -  11. Has difficulty in venous blood collection or halo acupuncture;&#xD;
&#xD;
          -  12.Blood donation / blood loss ≥200 mL within 1 month, or ≥400 mL within 3 months&#xD;
             before screening; or has blood donation plan during the period of medication of&#xD;
             investigational drugs and within 3 months after drug withdrawal;&#xD;
&#xD;
          -  13. Has special dietary requirements and cannot follow the unified dietary&#xD;
             arrangements;&#xD;
&#xD;
          -  14. Any conditions in which considered by investigator not be appropriate to&#xD;
             participate in this trial.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 21, 2020</last_update_submitted>
  <last_update_submitted_qc>June 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</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>
    <mesh_term>Bismuth</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/NCT04444011
org study id: 3571-DDI-1006
nct id: NCT04444011
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
A single-center, randomized, open-label, crossover study to evaluate the pharmacokinetic
      drug-drug interaction and safety of the quadruple therapy with Anaprazole 20mg/Amoxicilin
      1000mg/Clarithromycin 500mg/Bismuth Potassium Citrate 0.6g in healthy Chinese male subjects.
The study composed of 2 cohorts, using a 4*4 or 2*2 crossover design in cohort 1 and 2,
      respectively. 4 rotating treatment sequences in cohort 1, each treatment sequence comprised 4
      treatment periods, separated by a washout period of 9 days; 2 rotating treatment sequences in
      cohort 2, each treatment sequence comprised 2 treatment periods, separated by a washout
      period of 9 days
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cohort 1: Css,max of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)
time frame: Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 5，Day 19，Day 33，Day 47
description: Css,max is the peak plasma concentration at steady state
measure: Cohort 1: AUC of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)
time frame: Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 5，Day 19，Day 33，Day 47
description: AUC is area under the plasma concentration-time curve
measure: Cohort 2: Cmax of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)
time frame: Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 1，Day 11
description: Cmax is the peak plasma concentration
measure: Cohort 2: AUC of anaprazole (parent drug, KBP-3571) and its enantiomer（KBP-3570）and its major metabolites (KBP-1123 and KBP-1144), Unchanged amoxicillin, Unchanged clarithromycin and its metabolite (14-hydroxyclarithromycin)
time frame: Hour 0.5 pre-dose and 0.5，1，1.5，2，2.5，3，3.5，4，4.5，5，6，7，8，10，12，24 hours post-dose of Day 1，Day 11
description: AUC is area under the plasma concentration-time curve
measure: Number of subjects with adverse events and serious adverse events as assessed by CTCAE v5.0
time frame: From signing informed consent to study completion. 56 days minimum, 68 days maximum(Cohort 1); 30 days minimum, 32 days maximum(Cohort 2)
description: All adverse events will be monitored in each subject
arm group label: Anaprazole Sodium enteric-coated tablet
arm group type: Experimental
description: Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods of cohort 1 ( only once on the morning of D5 of treatment periods), one tablet each time.
arm group label: Amoxicillin capsules
arm group type: Experimental
description: "Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods of cohort 1 ( only once on the morning of D5 of treatment periods), 2 capsules each time.
arm group label: Clarithromycin tablet
arm group type: Experimental
description: "Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods of cohort 1 ( only once on the morning of D5 of treatment periods), 2 tablets each time.
arm group label: Anaprazole + Amoxicillin +Clarithromycin
arm group type: Experimental
description: "Cohort 1: Administered orally twice daily (e.g., 8am,8pm) for 5 consecutive days in 1 of 4 treatment periods ( only once on the morning of D5 of treatment periods).
Cohort 2: Administered orally on an empty stomach once on the morning of D1 of treatment periods
arm group label: Anaprazole + Amoxicillin +Clarithromycin+Bismuth
arm group type: Experimental
description: Administered orally on an empty stomach once on the morning of D1 of treatment periods in cohort 2
intervention type: Drug
intervention name: Anaprazole Sodium
description: Anaprazole Sodium isthePPI inhibitor
arm group label: Anaprazole + Amoxicillin +Clarithromycin
arm group label: Anaprazole + Amoxicillin +Clarithromycin+Bismuth
arm group label: Anaprazole Sodium enteric-coated tablet
intervention type: Drug
intervention name: Amoxicillin
description: antibiotic
arm group label: Amoxicillin capsules
arm group label: Anaprazole + Amoxicillin +Clarithromycin
arm group label: Anaprazole + Amoxicillin +Clarithromycin+Bismuth
intervention type: Drug
intervention name: Clarithromycin
description: antibiotic
arm group label: Anaprazole + Amoxicillin +Clarithromycin
arm group label: Anaprazole + Amoxicillin +Clarithromycin+Bismuth
arm group label: Clarithromycin tablet
intervention type: Drug
intervention name: Bismuth
description: Bismuth is to protect the gastric mucosa
arm group label: Anaprazole + Amoxicillin +Clarithromycin+Bismuth
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
mesh term: Amoxicillin
mesh term: Clarithromycin
mesh term: Bismuth