A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary purpose of the study is to evaluate the pharmacokinetics (what the body does to
      the medication) of intranasally (through the nose) administered esketamine in healthy
      participants.
    

Detailed description: 
      This is a single-center study with 3 cohorts (groups). Approximately 58 participants will be
      enrolled in this study. In Cohort 1, approximately 16 participants will be enrolled for up to
      78 days and they will receive 4 different single-dose regimens (Treatment A, B, C and D) of
      intranasal spray of esketamine solution in a crossover manner (participants will be switched
      from one single-dose regimen to another) and in an open label manner (both the investigator
      and the participant know the intervention received by the participant). In Cohort 2,
      approximately 14 participants will be enrolled for up to 35 days and they will receive 1
      regimen of intranasal esketamine (Treatment D) in an open label manner. In Cohort 3,
      approximately 28 participants will be enrolled and they will be randomly assigned to receive
      either Treatment E (intranasal esketamine spray) or Treatment F (intranasal placebo spray) in
      a double blind manner (both the investigator and the participant do not know the intervention
      received by the participant). Safety evaluations will include assessment of adverse events,
      targeted nasal examinations, laboratory tests, electrocardiogram, physical examination, pulse
      oximetery, and vital signs.
    

Intervention name(s): Esketamine; Placebo; Triazolam
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 1 spray of 14 percent of esketamine solution (14 mg of esketamine per 100 microlitre) will be administered intranasally by nasal spray pump in each nostril once (Treatment A-total dose: 28 mg), twice with 5 minutes interval (Treatment B-total dose: 56 mg), thrice with 5 minutes interval between each repeated sprays (Treatment C-total dose: 84 mg), thrice with 10 minutes interval between each repeated sprays (Treatment D-total dose: 84 mg) and 4 times with 10 minutes interval between each repeated sprays (Treatment E-total dose: 112 mg). Treatment A, B, C, D will be administered in Cohort 1; Treatment D will be administered in Cohort 2; and Treatment E will be administered in Cohort 3.; Single dose of oral placebo will be administered 5 minutes before the first intranasal spray of esketamine solution in the Treatment E of Cohort 3. Placebo solution (solution of water for injection with denatonium benzoate) will be administered intranasally solution by nasal spray pump in the Treatment F of Cohort 3.; Single 0.25-mg oral dose of triazolam will be administered 5 minutes before the first intranasal spray of placebo solution in the Treatment F of Cohort 3.
Intervention MeSH terms: Triazolam; Esketamine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Healthy; Esketamine; Pharmacokinetics; Intranasal