<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/NCT01711320</url>
  </required_header>
  <id_info>
    <org_study_id>20120925XJYYYJK</org_study_id>
    <nct_id>NCT01711320</nct_id>
  </id_info>
  <brief_title>Effect of Omeprazole on Metformin</brief_title>
  <official_title>Effect of Omeprazole, an OCT Inhibitor, on the Pharmacodynamics and Pharmacokinetics of Metformin, Involved the Mechanism of Attenuating AMPK Phosphorylation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xijing Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xijing Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, investigators hypothesized that the plasma concentration of metformin and its&#xD;
      glucose-lowering action would be affected by omeprazole, probably by altering the expression&#xD;
      or function of OCTs in the liver, its primary target organ, as well as in the kidney.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Metformin is the most widely used drug for the treatment of type 2 diabetes. This&#xD;
      insulin-sensitizing agent has well known beneficial effects not only on glycemic control, but&#xD;
      also on the cardiovascular system. The antihyperglycemic effect of metformin is mainly based&#xD;
      on suppression of hepatic gluconeogenesis by activation of AMP-activated protein kinase&#xD;
      (AMPK), which suppresses glucagon-stimulated glucose production and causes an increase in&#xD;
      glucose uptake in muscle and in hepatic cells. Metformin is actively transported across&#xD;
      membranes. The organic cation transporter 1 (OCT1) is responsible for uptake of metformin in&#xD;
      hepatocytes, which is an essential step in reducing hepatic glucose production. , which is&#xD;
      closely associated with its pharmacological action/adverse reactions.&#xD;
&#xD;
      However, metformin alone is thought to be insufficient for achieving good metabolic control.&#xD;
      Thus, treatment in addition to metformin is often required. Sitagliptin attenuates&#xD;
      metformin-mediated AMPK phosphorylation through inhibition of organic cation transporters&#xD;
      PPIs are frequently used in metformin-treated patients with metabolic syndrome and&#xD;
      cardiovascular diseases. Moreover, gastroesophageal reflux disease (GERD) is commonly seen in&#xD;
      patients with type 2 diabetes and proton-pump inhibitors (PPIs) are the drugs of best choice&#xD;
      in treatment of GERD. These data support the hypothesis that proton pump inhibitors can be&#xD;
      used to treat type II diabetes. Moreover, PPIs itself appears to has significant&#xD;
      glucose-lowering effects in an animal model of type 2 diabetes regardless of whether&#xD;
      metformin is administered concurrently.&#xD;
&#xD;
      A recent in-vitro study found that PPI inhibit metformin uptake by organic cation&#xD;
      transporters (OCTs). This drug-drug interaction the clinical has the potential relevance of&#xD;
      consequences on metformin disposition and/or efficacy. Since there is a possibility for the&#xD;
      combined use of metformin and omeprazole in chronic diabetics, the study is planned to&#xD;
      investigate the effect of nicorandil on the activity of gliclazide in normal and diabetic&#xD;
      rats to evaluate effectiveness of the combination.&#xD;
&#xD;
      The study is planned to find the pharmacodynamics and pharmacokinetics of metformin in the&#xD;
      presence of omeprazole in healthy subjects and to evaluate the mechanisms of the interaction&#xD;
      if occurs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">December 2012</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Whether the pharmacokinetics of metformin would be effected by omeprazole</measure>
    <time_frame>24 weeks</time_frame>
    <description>Pharmacokinetic parameters such as the area under the concentration-time curve (AUC), the elimination half-life(t½) and maximum metformin concentration (Cmax)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Whether the pharmacodynamics of metformin would be effected by omeprazole</measure>
    <time_frame>24 weeks</time_frame>
    <description>oral glucose tolerance tests (OGTTs) before and after receiving two doses of metformin</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>oral dose of Placebo combined with two dose of Metformin (OGTTs)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Omeprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral dose of Omeprazole (80 mg) combined with two dose of Metformin (OGTTs)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole</intervention_name>
    <arm_group_label>Omeprazole</arm_group_label>
    <other_name>PPI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age: 18 - 45 years&#xD;
&#xD;
          -  sex: male&#xD;
&#xD;
          -  body weight: 18 kg/m² to 26 kg/m²&#xD;
&#xD;
          -  good health as evidenced by the results of the clinical examination, ECG, and the&#xD;
             laboratory check-up, which are judged by the clinical investigator not to differ in a&#xD;
             clinical relevant way from the normal state&#xD;
&#xD;
          -  body weight: 18 kg/m² to 26 kg/m²&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  existing cardiac or hematological diseases and/or pathological findings which might&#xD;
             interfere with safety, pharmacodynamic effect and/or pharmacokinetics of metformin&#xD;
&#xD;
          -  existing hepatic and renal diseases and/or pathological findings which might interfere&#xD;
             with safety, pharmacodynamic effect and/or pharmacokinetics of metformin&#xD;
&#xD;
          -  existing gastrointestinal diseases and/or pathological findings which might interfere&#xD;
             with safety, pharmacodynamic effect and/or pharmacokinetics of metformin&#xD;
&#xD;
          -  acute or chronic diseases which could affect drug absorption or metabolism&#xD;
&#xD;
          -  history of any serious psychological disorder&#xD;
&#xD;
          -  drug or alcohol dependence&#xD;
&#xD;
          -  smokers of 10 or more cigarettes per day&#xD;
&#xD;
          -  positive screening results for HIV, HBV and HCV&#xD;
&#xD;
          -  volunteers who are on a diet which could affect the pharmacokinetics of the drug&#xD;
&#xD;
          -  heavy tea or coffee drinkers (more than 1L per day)&#xD;
&#xD;
          -  lactation and pregnancy test positive or not performed&#xD;
&#xD;
          -  volunteers suspected or known not to follow instructions&#xD;
&#xD;
          -  blood donation or other blood loss of more than 400 ml within the last 12 weeks prior&#xD;
             to the start of the study&#xD;
&#xD;
          -  participation in a clinical trial during the last 3 months prior to the start of the&#xD;
             study&#xD;
&#xD;
          -  less than 14 days after last acute disease&#xD;
&#xD;
          -  intake of grapefruit containing food or beverages within 7 days prior to&#xD;
             administration&#xD;
&#xD;
          -  any systemically available medication within 4 weeks prior to the intended first&#xD;
             administration unless, because of the terminal elimination half-life, complete&#xD;
             elimination from the body can be assumed for the drug and/or its primary metabolites&#xD;
             (except oral contraceptives)&#xD;
&#xD;
          -  repeated use of drugs during the last 4 weeks prior to the intended first&#xD;
             administration, which can influence hepatic biotransformation (e.g. barbiturates,&#xD;
             cimetidine, phenytoin, rifampicin)&#xD;
&#xD;
          -  repeated use of drugs during the last 2 weeks prior to the intended first&#xD;
             administration which affect absorption (e.g. laxatives, metoclopramide, loperamide,&#xD;
             antacids, H2-receptor antagonists)&#xD;
&#xD;
          -  known allergic reactions to the active ingredients used or to constituents of the&#xD;
             pharmaceutical preparation&#xD;
&#xD;
          -  subjects with severe allergies or multiple drug allergies&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>AiDong Wen, Pro</last_name>
    <role>Study Chair</role>
    <affiliation>Department of pharmacy, Xijing Hospital, Fourth Military Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of pharmacy, Xijing Hospital, Fourth Military Medical University</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2013</verification_date>
  <study_first_submitted>October 5, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>March 16, 2013</last_update_submitted>
  <last_update_submitted_qc>March 16, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 19, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Omeprazole</keyword>
  <keyword>Metformin</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Omeprazole</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/NCT01711320
org study id: 20120925XJYYYJK
nct id: NCT01711320
lead sponsor: 
has dmc: Yes
In this study, investigators hypothesized that the plasma concentration of metformin and its
      glucose-lowering action would be affected by omeprazole, probably by altering the expression
      or function of OCTs in the liver, its primary target organ, as well as in the kidney.
Metformin is the most widely used drug for the treatment of type 2 diabetes. This
      insulin-sensitizing agent has well known beneficial effects not only on glycemic control, but
      also on the cardiovascular system. The antihyperglycemic effect of metformin is mainly based
      on suppression of hepatic gluconeogenesis by activation of AMP-activated protein kinase
      (AMPK), which suppresses glucagon-stimulated glucose production and causes an increase in
      glucose uptake in muscle and in hepatic cells. Metformin is actively transported across
      membranes. The organic cation transporter 1 (OCT1) is responsible for uptake of metformin in
      hepatocytes, which is an essential step in reducing hepatic glucose production. , which is
      closely associated with its pharmacological action/adverse reactions.

      However, metformin alone is thought to be insufficient for achieving good metabolic control.
      Thus, treatment in addition to metformin is often required. Sitagliptin attenuates
      metformin-mediated AMPK phosphorylation through inhibition of organic cation transporters
      PPIs are frequently used in metformin-treated patients with metabolic syndrome and
      cardiovascular diseases. Moreover, gastroesophageal reflux disease (GERD) is commonly seen in
      patients with type 2 diabetes and proton-pump inhibitors (PPIs) are the drugs of best choice
      in treatment of GERD. These data support the hypothesis that proton pump inhibitors can be
      used to treat type II diabetes. Moreover, PPIs itself appears to has significant
      glucose-lowering effects in an animal model of type 2 diabetes regardless of whether
      metformin is administered concurrently.

      A recent in-vitro study found that PPI inhibit metformin uptake by organic cation
      transporters (OCTs). This drug-drug interaction the clinical has the potential relevance of
      consequences on metformin disposition and/or efficacy. Since there is a possibility for the
      combined use of metformin and omeprazole in chronic diabetics, the study is planned to
      investigate the effect of nicorandil on the activity of gliclazide in normal and diabetic
      rats to evaluate effectiveness of the combination.

      The study is planned to find the pharmacodynamics and pharmacokinetics of metformin in the
      presence of omeprazole in healthy subjects and to evaluate the mechanisms of the interaction
      if occurs.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Whether the pharmacokinetics of metformin would be effected by omeprazole
time frame: 24 weeks
description: Pharmacokinetic parameters such as the area under the concentration-time curve (AUC), the elimination half-life(t½) and maximum metformin concentration (Cmax)
measure: Whether the pharmacodynamics of metformin would be effected by omeprazole
time frame: 24 weeks
description: oral glucose tolerance tests (OGTTs) before and after receiving two doses of metformin
arm group label: Placebo
arm group type: Placebo Comparator
description: oral dose of Placebo combined with two dose of Metformin (OGTTs)
arm group label: Omeprazole
arm group type: Experimental
description: oral dose of Omeprazole (80 mg) combined with two dose of Metformin (OGTTs)
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Omeprazole
arm group label: Omeprazole
other name: PPI
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: AiDong Wen, Pro
role: Study Chair
affiliation: Department of pharmacy, Xijing Hospital, Fourth Military Medical University
facility: 
country: China
responsible party type: Sponsor
mesh term: Omeprazole