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
Study type: Interventional
Phase: Phase 1

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.
    

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 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.
    

Intervention name(s): Clopidogrel; Clopidogrel and Lansoprazole; Clopidogrel and Dexlansoprazole; Clopidogrel and Omeprazole; Clopidogrel and Esomeprazole
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Plavix; Plavix; Prevacid; AG-1749; Plavix; Kapidex; TAK-390MR; Plavix; Plavix; Nexium
Intervention MeSH terms: Esomeprazole; Omeprazole; Lansoprazole; Dexlansoprazole; Clopidogrel
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Keywords: Pharmacology; Stomach Ulcer; Esophagitis, Peptic; Zollinger-Ellison Syndrome; Platelet function; PPI; clopidogrel; Pharmacokinetics and Pharmacodynamics