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.
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 dexlansoprazole, lansoprazole, omeprazole or esomeprazole on the steady-state pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel in healthy participants. Participants were randomized equally into eight regimen sequence groups, 20 participants each. Participants randomized to Sequence Groups 1 and 2, 3 and 4, 5 and 6 and 7 and 8 were called proton pump inhibitor (PPI) Groups 1, 2, 3, and 4, respectively. Each sequence group consists of 2 regimens. Sequence Groups 1, 3, 5 and 7 dosed Regimen A (75 mg clopidogrel) for Days 1-9 of Period 1 and then crossed 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 \[2x40 mg\] omeprazole), or Regimen E (75 mg clopidogrel + 40 mg esomeprazole). Sequence Groups 2, 4, 6 and 8 began with either Regimen B, C, D or E for Period 1 and then crossed over to Regimen A for Period 2. On Day 9 of each period, blood samples were collected at predose and for 24 hours postdose to measure plasma concentrations of the active metabolite of clopidogrel. Platelet function was assessed daily prior to the dose of clopidogrel on Days 7-9 and 24-hours post Day 9 dose in each period. There was 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 participants were 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
160
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.
Unnamed facility
Tempe, Arizona, United States
Pharmacokinetic Parameter Peak Plasma Concentration (Cmax) of Clopidogrel's Active Metabolite.
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Day 9 of each period
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.
Area under the plasma concentration versus time curve (AUC(0-tlqc)) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
Time frame: Day 9 of each period
Pharmacodynamic Parameter Platelet Reactivity Index (PRI) From Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation State (Flow Cytometry).
PRI is the platelet reactivity index from VASP phosphorylation state (flow cytometry).
Time frame: 24-hour post Day 9 dose in each period.
Pharmacodynamic Parameter Maximum Platelet Aggregation (MPA) From Aggregometry (Turbidimetric) With 5 µM Adenosine Diphosphate.
Maximum platelet aggregation (MPA) from aggregometry (turbidimetric) with 5 µM adenosine diphosphate.
Time frame: 24-hour post Day 9 dose in each period.
Pharmacodynamic Parameter MPA From Aggregometry (Turbidimetric) With 20 µM Adenosine Diphosphate.
MPA from aggregometry (turbidimetric) with 20 µM adenosine diphosphate.
Time frame: 24-hour post Day 9 dose in each period.
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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.