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A Study of the Effects of Multiple Doses of Dexlansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Subjects.
This study is currently recruiting participants.
Verified by Takeda Global Research & Development Center, Inc., January 2010
First Received: July 16, 2009   Last Updated: January 5, 2010   History of Changes
Sponsor: Takeda Global Research & Development Center, Inc.
Information provided by: Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier: NCT00942175
  Purpose

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


Condition Intervention Phase
Healthy
Drug: Clopidogrel
Drug: Clopidogrel and Lansoprazole
Drug: Clopidogrel and Dexlansoprazole
Drug: Clopidogrel and Omeprazole
Drug: Clopidogrel and Esomeprazole
Phase I

Study Type: Interventional
Study Design: Randomized, Open Label, Crossover Assignment, Pharmacokinetics/Dynamics Study
Official Title: A Phase 1, Randomized, Open-Label, 2-Period, Crossover Design Study to Assess the Effects of Multiple Oral Doses of Dexlansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Steady-State Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:
  • Pharmacokinetic parameter peak plasma concentration (Cmax) of clopidogrel's active metabolite. [ Time Frame: Day 9 of each period ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter area under the plasma concentration versus time curve (AUC) from time 0 to time of the last quantifiable concentration (AUC[0-tlqc]) of clopidogrel's active metabolite. [ Time Frame: Day 9 of each period ] [ Designated as safety issue: No ]
  • Pharmacodynamic parameter Platelet Reactivity Index (PRI) from vasodilator-stimulated phosphoprotein (VASP) phosphorylation state (flow cytometry). [ Time Frame: 24-hour post Day 9 dose in each period. ] [ Designated as safety issue: No ]
  • Pharmacodynamic parameter Maximum Platelet Aggregation (MPA) from aggregometry (turbidimetric) with 5 and 20 µM ADP. [ Time Frame: 24-hour post Day 9 dose in each period. ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: January 2010
Estimated Study Completion Date: July 2010
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Regimen A
Clopidogrel 75 mg QD
Drug: Clopidogrel
Clopidogrel 75 mg, tablets, orally, once daily days 1-9.
Regimen B
Clopidogrel 75 mg QD and Lansoprazole 30 mg QD
Drug: Clopidogrel and Lansoprazole
Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily days 1-9.
Regimen C
Clopidogrel 75 mg QD and Dexlansoprazole 60 mg QD
Drug: Clopidogrel and Dexlansoprazole
Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily days 1-9.
Regimen D
Clopidogrel 75 mg QD and Omeprazole 80 mg QD
Drug: Clopidogrel and Omeprazole
Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily days 1-9.
Regimen E
Clopidogrel 75 mg QD and Esomeprazole 40 mg QD
Drug: Clopidogrel and Esomeprazole
Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily days 1-9.

Detailed Description:

This is a Phase 1, randomized, open-label, single-center, multiple-dose, 2-period, crossover study to assess the effects of multiple oral doses of once daily (QD) dexlansoprazole, lansoprazole, omeprazole or esomeprazole on the steady-state pharmacokinetics (PK) and pharmacodynamics of clopidogrel in healthy subjects.

Subjects will be randomized equally into eight regimen sequence groups, 20 subjects each. Subjects who are randomized to Sequence Groups 1 and 2, 3 and 4, 5 and 6 and 7 and 8 are called PPI Groups 1, 2, 3, and 4, respectively. Each sequence group will consist of 2 regimens. Sequence Groups 1, 3, 5 and 7 will dose Regimen A (75 mg clopidogrel) for Days 1-9 of Period 1 and then will cross over to one of the following 4 regimens for Days 1-9 of Period 2: Regimen B (75 mg clopidogrel + 30 mg lansoprazole), Regimen C (75 mg clopidogrel + 60 mg dexlansoprazole), Regimen D (75 mg clopidogrel + 80 mg omeprazole), or Regimen E (75 mg clopidogrel + 40 mg esomeprazole). Sequence Groups 2, 4, 6 and 8 will begin with either Regimen B, C, D or E for Period 1 and will then cross over to Regimen A for Period 2.

On Day 9 of each period, blood samples will be collected at predose and for 24 hours postdose to measure plasma concentrations of the active metabolite of clopidogrel. Platelet function will be assessed daily prior to the dose of clopidogrel on Days 7-9 and 24-hours post Day 9 dose in each period. There will be a washout interval of 10 to 14 days between the last dose of study drug in Period 1 and the first dose of study drug in Period 2.

Study subjects will be confined to the study center for 10 consecutive nights in Period 1, followed by a 10- to 14-day washout interval and confined for an additional 10 consecutive nights in Period 2.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.
  • Must be a CYP2C19 extensive metabolizer (wt/wt).
  • Female participants of childbearing potential cannot be nursing, must have a negative serum pregnancy test at Check-in (Day 1 of Period 1), and use barrier contraception, or continuously practice abstinence throughout the duration of the study and for 30 days after the last dose of study drug.
  • 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.
  • 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.
  • 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.
  • 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:

  • 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.
  • 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.
  • Has a history of drug abuse or a history of alcohol abuse within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
  • 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.
  • 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.
  • 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 subject to participate or potentially confound the trial results.
  • 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.
  • Has had an acute, clinically significant illness within 30 days prior to the first dose of study drug.
  • 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).
  • 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).
  • 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 subject from entering the study.
  • 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.
  • Has used nicotine-containing products 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.
  • With the exception of acetaminophen, has taken any excluded medication, supplements or food products listed in the Excluded Dietary Items and Medications table.
  • 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
  • Has a positive test result for caffeine at the Check-in (Day -1 of Period 1) Visit.
  • 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.
  • Has received clopidogrel or any PPIs or histamine2-receptor antagonists within 28 days of screening.
  • Subject, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00942175

Contacts
Contact: Takeda Study Registration Call Center 800-778-2860 medicalinformation@tpna.com

Locations
United States, Arizona
Recruiting
Phoenix, Arizona, United States
Sponsors and Collaborators
Takeda Global Research & Development Center, Inc.
Investigators
Study Director: Medical Director Clinical Science Takeda Global Research & Development Center, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers: TAK-390MR_101, U1111-1112-6792
Study First Received: July 16, 2009
Last Updated: January 5, 2010
ClinicalTrials.gov Identifier: NCT00942175     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:
Pharmacology
Stomach Ulcer
Esophagitis, Peptic
Zollinger-Ellison Syndrome
Platelet function
PPI
clopidogrel
Pharmacokinetics and Pharmacodynamics

Additional relevant MeSH terms:
Anti-Infective Agents
Ticlopidine
Molecular Mechanisms of Pharmacological Action
Hematologic Agents
Gastrointestinal Agents
Omeprazole
Fibrinolytic Agents
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents
Clopidogrel
Therapeutic Uses
Anti-Ulcer Agents
Platelet Aggregation Inhibitors
Lansoprazole

ClinicalTrials.gov processed this record on February 08, 2010