A Study to Assess the Pharmacokinetics of Intranasally Administered Esketamine in Healthy Japanese and Caucasian Volunteers

This is an open-label single-center study with 2 cohorts (groups). The study will consist of
a screening phase, a treatment phase, and a follow-up visit (9 to 13 days after the last
dose of the study drug). During the screening phase, participants will be evaluated to
determine if they meet the study eligibility criteria. A target of 14 healthy Japanese and
14 healthy Caucasian adult participants (20 to 55 years of age inclusive) will be enrolled
in Cohort 1 and Cohort 2, respectively.

The participants in each cohort will self-administer each of the 3 different single-dose
regimens of intranasal esketamine (Treatments A, B, and C) over the 3 treatment periods (ie,
1 treatment per period) in an open-label manner (both the investigator and the participant
knows which intervention the participant receives). The participants will be randomly (like
the toss of a coin) assigned to receive Treatment A and Treatment B in the first two periods
(ie, Treatment A in Period 1 and Treatment B in Period 2, or the reverse order). All
participants will receive Treatment C in Period 3. The regimens differ in the number of
sprays to achieve the total dose and the total esketamine dose administered.

Safety and tolerability will be evaluated throughout the study and will include assessment
of adverse events, targeted nasal examinations, laboratory tests, electrocardiogram,
physical examination, pulse oximetery, and vital signs.

Inclusion Criteria:

- Healthy Japanese (Cohort 1) or Caucasian (Cohort 2) man or woman, between 20 to 55
years of age

- Resided outside of Japan for no more than 5 years and have parents and maternal and
paternal grandparents who are of Japanese ethnicity

- Blood pressure (after the participant is in the supine position for 5 minutes)
between 90 and 145 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic

- A 12-lead electrocardiogram consistent with normal cardiac conduction and function

- Smokes no more than 10 cigarettes, or 2 cigars, or 2 pipes of tobacco per day for at
least 6 months before first study drug administration

- Comfortable with self-administration of intranasal medication and able to follow
instructions provided

Exclusion criteria:

- History of or current clinically significant medical illness including (but not
limited to) cardiac arrhythmias or other cardiac disease; hematologic disease;
coagulation disorders (including any abnormal bleeding or blood dyscrasias);
hypertension or vascular disorders; significant pulmonary disease, including any
bronchospastic respiratory disease; diabetes mellitus; renal or hepatic
insufficiency; thyroid disease; neurologic or psychiatric disease, infection;
kidney/urinary tract disturbances; sleep apnea, or myasthenia gravis, or any other
illness that the investigator considers should exclude the participant or that could
interfere with the interpretation of the study results

- Clinically significant abnormal values for hematology, clinical chemistry, or
urinalysis at screening or at admission to the study center

- Anatomical or medical conditions that may impede delivery or absorption of study
medication

- Has an abnormal or deviated nasal septum with any 1 or more of the following
symptoms: blockage of 1 or both nostrils, nasal congestion (especially 1-sided),
frequent nosebleeds, frequent sinus infections, noisy breathing during sleep, and at
times has facial pain, headaches, and postnasal drip

- Has a current diagnosis of a psychotic disorder, bipolar disorder, mental
retardation, or borderline personality disorders; mood disorder with postpartum
onset, somatoform disorders, fibromyalgia, or chronic fatigue syndrome; generalized
anxiety disorder, panic disorder, obsessive compulsive disorder, posttraumatic stress
disorder, anorexia nervosa, or bulimia nervosa