<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/NCT03234699</url>
  </required_header>
  <id_info>
    <org_study_id>YKP3089C026</org_study_id>
    <nct_id>NCT03234699</nct_id>
  </id_info>
  <brief_title>Assess the Influence of Cenobamate on the PK of Cytochrome P450 (CYP) Probe Drugs as a Means of Predicting Drug-drug Interactions</brief_title>
  <official_title>The Effect of Multiple Doses of Cenobamate (YKP3089) on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Midazolam, Warfarin, Omeprazole and Bupropion) Administered Orally in an Open-label, One-sequence Study in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SK Life Science, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SK Life Science, Inc.</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>
      This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5,&#xD;
      CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo&#xD;
      probes. In order to avoid a potential pharmacokinetic interaction between the probes,&#xD;
      midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together&#xD;
      as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time&#xD;
      period between the 2 assessments.&#xD;
&#xD;
      The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2&#xD;
      weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg,&#xD;
      150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady&#xD;
      state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day&#xD;
      of cenobamate for all CYP probes.&#xD;
&#xD;
      The results of this DDI study will provide a basis to make appropriate dose recommendation&#xD;
      for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic&#xD;
      pathway.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 22, 2017</start_date>
  <completion_date type="Actual">July 31, 2017</completion_date>
  <primary_completion_date type="Actual">July 3, 2017</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>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic parameters AUC</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters Cmax</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters AUC</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters Cmax</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters AUC (to infinity)</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter RAUC (ratio of metabolite to parent)</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for 5-OH omeprazole/omeprazole, 1-OH midazolam/midazolam, S,S-OH-bupropion/S-bupropion, R,R-OH-bupropion/R-bupropion, total OH-bupropion/total bupropion, threohydrobupropion/R-bupropion</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacokinetic parameters tmax</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic parameters Ctz</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic parameters tz</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic parameters t1/2</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic parameters CL/F</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic parameters Vz/F</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetic parameters Cmin</measure>
    <time_frame>bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)</time_frame>
    <description>Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Single Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cenobamate</intervention_name>
    <description>12.5 mg q.d.(Days 13-26), 25 mg q.d. (Days 27-40), 50 mg q.d. (Days 41-54), 100 mg q.d. (Days 55-70), 150 mg q.d. (Days 71-84), 200 mg q.d. (Days 85-110)</description>
    <arm_group_label>Single Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>midazolam</intervention_name>
    <description>2 mg midazolam syrup (Days 7, 69, 105)</description>
    <arm_group_label>Single Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin Pill</intervention_name>
    <description>5 mg (Days 7 and 105)</description>
    <arm_group_label>Single Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole Pill</intervention_name>
    <description>20 mg (Days 7 and 105)</description>
    <arm_group_label>Single Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupropion Pill</intervention_name>
    <description>150 mg (Days 1 and 99)</description>
    <arm_group_label>Single Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects between 18 to 50 years of age inclusive&#xD;
&#xD;
          2. Subject is willing and able to provide informed consent&#xD;
&#xD;
          3. Body mass index (BMI) within 19.0 kg/m2 and 29.9 kg/m2, inclusive, at screening&#xD;
&#xD;
          4. Subject is a non- or ex-smoker and has not used any nicotine containing products&#xD;
             within 6 months prior to screening&#xD;
&#xD;
          5. Subjects who are considered generally healthy upon completion of medical history,&#xD;
             physical examination, vital signs, screening laboratory results and screening ECG in&#xD;
             the opinion of the Investigator&#xD;
&#xD;
          6. Subjects who are willing and able to comply with the dosing/visit schedule, laboratory&#xD;
             tests, pharmacokinetic sampling schedule, and other study procedures&#xD;
&#xD;
          7. A female study subject must meet one of the following criteria:&#xD;
&#xD;
             If of childbearing potential - agrees to use one of the accepted contraceptive&#xD;
             regimens from screening, during the study and for at least 30 days after the last dose&#xD;
             of the study medication. Hormonal contraceptives alone will not be considered an&#xD;
             adequate method of contraception. An acceptable method of contraception includes one&#xD;
             of the following:&#xD;
&#xD;
               1. Diaphragm and spermicide&#xD;
&#xD;
               2. Condom with spermicide&#xD;
&#xD;
               3. Sponge and spermicide&#xD;
&#xD;
               4. Intrauterine device (with or without hormones; placement at least 3 months prior&#xD;
                  to Screening) in combination with a barrier method&#xD;
&#xD;
               5. Oral contraceptives, Depo-Provera, Norplant, Patch or intrauterine progesterone&#xD;
                  contraceptive for at least 90 days prior to screening in combination with a&#xD;
                  barrier method.&#xD;
&#xD;
               6. Vasectomized partner (6 months minimum since vasectomy)&#xD;
&#xD;
               7. Complete abstinence from heterosexual intercourse. However, if the subject&#xD;
                  becomes sexually active, 1 of the above methods must be utilized.&#xD;
&#xD;
             If a female of non-childbearing potential - should be surgically sterile (i.e. has&#xD;
             undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation at least 6&#xD;
             months prior to Screening) or in a menopausal state (at least 1 year without menses),&#xD;
             as confirmed by FSH levels (post menopausal must be confirmed by the subject having a&#xD;
             serum follicle stimulating hormone greater than 40mIU/ml at screening)&#xD;
&#xD;
          8. A female study subject must agree not to donate eggs during the study and for at least&#xD;
             30 days after the last dose of the study medication&#xD;
&#xD;
          9. A male study subject must agree to use one of the accepted contraceptive regimens&#xD;
             during the study and for at least 90 days after the last dose of the study&#xD;
             medications;&#xD;
&#xD;
               1. Abstinence from heterosexual intercourse. However, if the subject becomes&#xD;
                  sexually active, 1 of the below methods must be utilized&#xD;
&#xD;
               2. Female partner with hormonal contraceptives (birth control pills,&#xD;
                  injectable/implant/insertable hormonal birth control products, transdermal patch)&#xD;
                  in combination with a barrier method&#xD;
&#xD;
               3. Female partner with intrauterine device (with or without hormones) in combination&#xD;
                  with a barrier method&#xD;
&#xD;
               4. Female partner with condom with spermicide used by male study subject&#xD;
&#xD;
               5. Female partner of non-childbearing potential&#xD;
&#xD;
               6. Female partner with diaphragm with spermicide&#xD;
&#xD;
               7. Female partner with sponge and spermicide&#xD;
&#xD;
               8. Male sterilization with absence of sperm in the post vasectomy ejaculate for ≥ 6&#xD;
                  months&#xD;
&#xD;
         10. A male study subject must agree not to donate sperm during the study and for at least&#xD;
             90 days after the last dose of the study medication&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Females who are breastfeeding&#xD;
&#xD;
          2. Inadequate venous access&#xD;
&#xD;
          3. History of any drug related hypersensitivity reactions as well as severe&#xD;
             hypersensitivity reactions (like angioedema), or DRESS syndrome to any drugs in the&#xD;
             opinion of the Investigator&#xD;
&#xD;
          4. History of 1st degree relative having a serious cutaneous adverse reaction&#xD;
&#xD;
          5. Current clinically significant rash&#xD;
&#xD;
          6. Clinically significant history or evidence of gastrointestinal, hepatic, renal,&#xD;
             endocrine, pulmonary, neurological, psychiatric, cardiovascular, hematologic,&#xD;
             dermatologic, immunologic disease or any other condition known to interfere with the&#xD;
             absorption, distribution, metabolism or elimination of drugs that in the opinion of&#xD;
             the Investigator would jeopardize the safety of the subject or impact validity of&#xD;
             study results&#xD;
&#xD;
          7. History of hepatic impairment, cholecystectomy, renal impairment or any other&#xD;
             condition known to interfere with the absorption, distribution, metabolism or&#xD;
             elimination of orally administered drug&#xD;
&#xD;
          8. Presence of observed abnormality (evidenced from physical examination, ECG, vital&#xD;
             signs, or laboratory evaluation) that would be clinically significant in the opinion&#xD;
             of the Investigator&#xD;
&#xD;
          9. Current evidence or history of suicidal tendency, seizures, state of confusion or any&#xD;
             other clinically relevant psychiatric disease.&#xD;
&#xD;
         10. Subject is at imminent risk of suicide (positive response to question 4 or 5 on the&#xD;
             C-SSRS) or had a suicide attempt within 6 months prior to the screening visit&#xD;
&#xD;
         11. History of regular alcohol consumption exceeding 7 drinks per week for females and 14&#xD;
             drinks per week for males within 6 months prior to screening&#xD;
&#xD;
         12. Has current or recent history (within the past year) of alcohol or drug abuse or&#xD;
             dependence&#xD;
&#xD;
         13. Any clinically significant illness in the previous 30 days prior to screening&#xD;
&#xD;
         14. Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as&#xD;
             cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole,&#xD;
             ketoconazole, diltiazem, and HIV antivirals) and strong inducers of CYP enzymes (such&#xD;
             as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's&#xD;
             Wort) in the previous 30 days prior to Day 1 of this study&#xD;
&#xD;
         15. Use of all drugs associated with DRESS syndrome such as phenobarbital, carbamazepine,&#xD;
             phenytoin, lamotrigine, minocycline, sulfonamides, allopurinol, modafinil, dapsone,&#xD;
             ziprasidone, vancomycin and olanzapine in the previous 6 months prior to Day 1 of this&#xD;
             study&#xD;
&#xD;
         16. Clinically-relevant, unusual dietary habits (e.g., vegan, Atkins), dietary&#xD;
             restrictions, and/or food allergies&#xD;
&#xD;
         17. Positive urine screen for alcohol and/or drugs of abuse at screening and at each&#xD;
             admission&#xD;
&#xD;
         18. Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg)&#xD;
             or Hepatitis C Antibody (HCVAb) at screening&#xD;
&#xD;
         19. Has been administered any investigational drug 30 days (or 6 times its terminal&#xD;
             half-live) prior to Day 1 of this study&#xD;
&#xD;
         20. Females with a positive pregnancy test at screening, regardless of child-bearing&#xD;
             potential prior to Day 1 of this study&#xD;
&#xD;
         21. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days&#xD;
             prior to screening&#xD;
&#xD;
         22. Subject is unlikely to comply with the study protocol or, in the opinion of the&#xD;
             Investigator, would not be a suitable candidate for participation in the trial&#xD;
&#xD;
         23. Anyone who has previously been exposed to cenobamate (prior to participation in this&#xD;
             study)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Vince and Associates Clinical Research, Inc.</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>April 17, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>August 7, 2017</last_update_submitted>
  <last_update_submitted_qc>August 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 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>Midazolam</mesh_term>
    <mesh_term>Cenobamate</mesh_term>
    <mesh_term>Bupropion</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
    <mesh_term>Warfarin</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/NCT03234699
org study id: YKP3089C026
nct id: NCT03234699
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is aimed to investigate the influence of cenobamate on the activity of CYP3A4/5,
      CYP2B6, CYP2C19, and CYP2C9 by using drugs recommended by both the FDA and EMA as in vivo
      probes. In order to avoid a potential pharmacokinetic interaction between the probes,
      midazolam (CYP3A), warfarin (CYP2C9), and omeprazole (CYP2C19) will be administered together
      as a validated cocktail and separately from bupropion (CYP2B6) using an adequate washout time
      period between the 2 assessments.

      The starting daily dose of cenobamate will be 12.5 mg, which will be administered for 2
      weeks. Then, daily cenobamate doses will be increased every 2 weeks to 25 mg, 50 mg, 100 mg,
      150 mg, and 200 mg. The CYP probes will be tested before cenobamate administration, at steady
      state at 100mg/day of cenobamate for midazolam only and finally at steady state at 200mg/day
      of cenobamate for all CYP probes.

      The results of this DDI study will provide a basis to make appropriate dose recommendation
      for a safe use of concomitant drugs with cenobamate using these isoenzymes in their metabolic
      pathway.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: Pharmacokinetic parameters AUC
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state
measure: Pharmacokinetic parameters Cmax
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for S- and R-bupropion, total bupropion, midazolam, S-warfarin and R-warfarin, and omeprazole when administered with and without cenobamate at steady state
measure: Pharmacokinetic parameters AUC
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)
measure: Pharmacokinetic parameters Cmax
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)
measure: Pharmacokinetic parameters AUC (to infinity)
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for probe drug metabolites (S,S-hydroxybupropion and R,R-hydroxybupropion, threohydrobupropion, 1-hydroxymidazolam, and 5-OH omeprazole)
measure: Pharmacokinetic parameter RAUC (ratio of metabolite to parent)
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for 5-OH omeprazole/omeprazole, 1-OH midazolam/midazolam, S,S-OH-bupropion/S-bupropion, R,R-OH-bupropion/R-bupropion, total OH-bupropion/total bupropion, threohydrobupropion/R-bupropion
measure: Pharmacokinetic parameters tmax
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state
measure: Pharmacokinetic parameters Ctz
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state
measure: Pharmacokinetic parameters tz
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state
measure: Pharmacokinetic parameters t1/2
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state
measure: Pharmacokinetic parameters CL/F
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state
measure: Pharmacokinetic parameters Vz/F
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state
measure: Pharmacokinetic parameters Cmin
time frame: bupropion (6 days), midazolam (24 hrs), omeprazole (24 hrs), warfarin (7 days)
description: Will be determined for the probe drugs (and metabolites) when administered with or without cenobamate at steady state
arm group label: Single Group
arm group type: Experimental
intervention type: Drug
intervention name: Cenobamate
description: 12.5 mg q.d.(Days 13-26), 25 mg q.d. (Days 27-40), 50 mg q.d. (Days 41-54), 100 mg q.d. (Days 55-70), 150 mg q.d. (Days 71-84), 200 mg q.d. (Days 85-110)
arm group label: Single Group
intervention type: Drug
intervention name: midazolam
description: 2 mg midazolam syrup (Days 7, 69, 105)
arm group label: Single Group
intervention type: Drug
intervention name: Warfarin Pill
description: 5 mg (Days 7 and 105)
arm group label: Single Group
intervention type: Drug
intervention name: Omeprazole Pill
description: 20 mg (Days 7 and 105)
arm group label: Single Group
intervention type: Drug
intervention name: Bupropion Pill
description: 150 mg (Days 1 and 99)
arm group label: Single Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Midazolam
mesh term: Cenobamate
mesh term: Bupropion
mesh term: Omeprazole
mesh term: Warfarin
sharing ipd: No