A Study of the Effects of Multiple Doses of Dexlansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Participants.
Condition: Healthy
Intervention: Clopidogrel; Clopidogrel and Lansoprazole; Clopidogrel and Dexlansoprazole; Clopidogrel and Omeprazole; Clopidogrel and Esomeprazole
Intervention description: Clopidogrel 75 mg, tablets, orally, once daily days 1-9.; Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily days 1-9.; Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily days 1-9.; Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily days 1-9.; Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily days 1-9.
Intervention MeSH terms: Esomeprazole; Omeprazole; Lansoprazole; Dexlansoprazole; Clopidogrel
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacology; Stomach Ulcer; Esophagitis, Peptic; Zollinger-Ellison Syndrome; Platelet function; PPI; clopidogrel; Pharmacokinetics and Pharmacodynamics

Summary:

      The purpose of this study is to assess the potential effect and safety of multiple oral doses
      of dexlansoprazole, lansoprazole, omeprazole or esomeprazole, once daily (QD), on the
      steady-state pharmacokinetics and pharmacodynamics of clopidogrel, and to assess the safety
      of multiple doses of clopidogrel in healthy participants.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The participant or the participant's legally acceptable representative signs a
             written, informed consent form prior to the initiation of any study procedures.

          2. Weighs at least 50 kg and has a body mass index (BMI) between 18 and 30 kg/m2,
             inclusive, at Screening and Check-in (Day -1 of Period 1) Visits.

          3. Must be a CYP2C19 extensive metabolizer (wt/wt).

          4. Females cannot be nursing and must have a negative urine pregnancy test at Day -1 or
             be of non-childbearing potential. If females are of child bearing potential, must have
             a negative serum human chorionic gonadotropin (hCG) pregnancy test during Screening
             and on an acceptable form of contraception, or have had bilateral tubal ligation if
             performed a minimum of 90 days prior to Day 1.

          5. At the Screening and Check-in (Day -1 of Period 1) Visits, must have an estimated
             creatinine clearance (CLcr) greater than or equal 90 mL/minute as determined from the
             Cockcroft-Gault formula.

          6. Is in good health as determined by a physician based upon medical history,
             electrocardiogram, and physical examination findings at the Screening and Check-in
             (Day -1 of Period 1) Visits.

          7. Participant's clinical laboratory evaluations (including hematology, clinical
             chemistry [fasted for a least 8 hours], and urinalysis) at the Screening and Check-in
             (Day -1 of Period 1) Visits are within the reference range for the testing laboratory
             or are deemed not clinically significant by the investigator and TGRD Medical Monitor.

          8. Participant's urine drug screen for selected substances of abuse is negative at the
             Screening and Check-in (Day -1 of Period 1) Visits.

        Exclusion Criteria:

          1. Has consumed products containing Seville oranges (sour), grapefruit or grapefruit
             juice within 14 days prior to the first dose of study drug or is unwilling to agree to
             abstain from products containing Seville oranges (sour), grapefruit or grapefruit
             juice while participating in the study.

          2. Has current or recent (within 6 months) gastrointestinal disease, a history of
             malabsorption, esophageal reflux, gastric bleeding or peptic ulcer disease, frequent
             (more than once per week) occurrence of heartburn, or any surgical intervention (eg,
             cholecystectomy), which would be expected to influence the absorption of drugs.

          3. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse (defined as the consumption of more than 4 alcoholic beverages per day) within 1
             year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and
             drugs throughout the study.

          4. Is currently participating in another investigational study or has received any
             investigational compound within 30 days prior to the Check-in (Day -1 of Period 1)
             Visit.

          5. Has received any known hepatic or renal clearance altering agents (eg, erythromycin,
             cimetidine, barbiturates, phenothiazines, fluvoxamine, etc.) within 28 days prior to
             first dose of study drug.

          6. Has a history or clinical manifestations of significant metabolic, hematologic,
             pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urologic,
             immunologic, or psychiatric disorder as determined by the investigator which may
             impact the ability of the participant to take part in or potentially confound the
             trial results.

          7. Has a history of hypersensitivity or allergies to any drug or food or any excipients
             of clopidogrel, lansoprazole, dexlansoprazole, omeprazole, esomeprazole or other drug
             with the same mechanism of action or related compounds.

          8. Has had an acute, clinically significant illness within 30 days prior to the first
             dose of study drug.

          9. Has a systolic blood pressure greater than 140 mm Hg or has a diastolic blood pressure
             greater than 90 mm Hg at Screening or Check-in (Day -1 of Period 1).

         10. Has a positive test result for hepatitis B surface antigen (HBsAg) or antibody to
             hepatitis C virus (anti-HCV) at Screening, or a known history of infection with the
             human immunodeficiency virus (HIV).

         11. Has a Day -1 laboratory value assessed by the principal investigator and sponsor
             medical monitor as clinically significant underlying disease or condition that may
             prevent the participant from entering the study.

         12. Has an alanine aminotransferase, aspartate aminotransferase or Total Bilirubin level
             that exceeds the upper limit of normal at the Screening or Check-in (Day -1 of Period
             1) Visits.

         13. Has used nicotine-containing products (including but not limited to cigarettes, pipes,
             cigars, chewing tobacco, nicotine patch or nicotine gum) within 6 weeks prior to
             Check-in (Day -1 of Period 1) Visit, or has a positive cotinine screen at the
             Screening or Check-in (Day - 1 of Period 1) Visits or anticipates an inability to
             abstain from these products for the duration of the study.

         14. With the exception of acetaminophen, has taken any excluded medication, supplements or
             food products listed in the Excluded Dietary Items and Medications table located in
             the study protocol.

         15. Has donated blood products (such as plasma) within 30 days, or has donated whole blood
             or had a significant blood loss (500 mL) within 56 days of the first dose of study
             drug

         16. Has a positive test result for caffeine at the Check-in (Day -1 of Period 1) Visit.

         17. Has a history of cancer, except basal cell carcinoma, which has not been in remission
             for at least 5 years prior to the first dose of study drug.

         18. Has received clopidogrel or any PPIs or histamine2-receptor antagonists within 28 days
             of screening.

         19. Participant, in the opinion of the investigator, is unlikely to comply with the
             protocol or is unsuitable for any other reason.