The purpose of this study is to assess the cognitive effects associated with administration of intranasal esketamine 84 mg.
This is a randomized (participants assigned to 1 of 2 treatment sequences by chance), double-blind (identity of study drugs will not be known to participant or members of study staff), placebo-controlled (a substance without active drug identical in appearance to esketamine), 2-period crossover study (participants assigned to each treatment sequence will receive 1 dose of esketamine and 1 dose of placebo administered intranasally \[through the nose\]) conducted in healthy adult participants at a single center. Participants will complete 3 study phases: A screening phase of up to 3 weeks; a 2-week double-blind treatment phase, which includes 2 treatment periods (Periods 1 and 2) separated by a washout interval of at least 7 days; and, a 1-week posttreatment (follow up) phase, if applicable. The duration of the study for each participant will be approximately 6 weeks. Blood and urine samples will be collected during the study for laboratory assessments. Participants will be monitored for safety from the time of signing the informed consent form up until 1 week after the last dose of study drug (or end of treatment).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
24
84 mg esketamine administered intranasally
Placebo administered intranasally
Unnamed facility
Leiden, Netherlands
Change from baseline in cognitive functioning measured by the The Cogstate® Computerized Battery
The Cogstate® Computerized Battery of tests will include 5 tests: Detection (simple reaction time task measuring processing speed \[lower score = better performance\]); Identification (choice reaction time paradigm measuring attention \[lower score = better performance\]); One Card Learning (visual episodic memory measure \[higher score = better performance\]); One Back ( "n-back" working memory measure \[higher score = better performance\]); and, Groton Maze Learning Test (executive function measure; total number of errors made in attempting to learn the same hidden pathway on five consecutive trials at a single session \[lower score = better performance\]) (Maruff 2004, Snyder 2005).
Time frame: On Day 1 at -1 hour, 40 minutes, and at 2, 4, and 6 hours after dosing (or at the end of treatment)
Change from baseline in cognitive functioning measured by the Karolinska Sleepiness Scale (KSS)
The KSS is a subject-reported assessment used to rate sleepiness on a scale of 1 to 9, ranging from 'extremely alert' (1) to 'very sleepy, great effort to keep awake, fighting sleep' (9) (Akerstedt 1990).
Time frame: On day 1 at -1 hour, 40 minutes, and at 2, 4, and 6 hours after dosing (or at the end of treatment)
Change from baseline in cognitive functioning measured by the mental effort scale
The mental effort scale is a subject-reported assessment of the level of effort needed to complete the test battery on a 15-cm equal interval scale (Zijlstra1993).
Time frame: On Day 1 at -1 hour, 40 minutes, and at 2, 4, and 6 hours after dosing (or at the end of treatment)
The concentration of esketamine and noresketamine from time zero to the last observable concentration (AUClast)
Time frame: Day 1 at 0, 10, and 40 minutes and 1, 2, and 4 hours after dosing
The maximum plasma concentration (Cmax) of esketamine and noresketamine
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Time frame: Day 1 at 0,10, and 40 minutes and at 1, 2, 4, and 6 hours after dosing
Time to Maximum Plasma Concentration (Tmax) of esketamine and noresketamine
Time frame: Day 1 at 0, 10, and 40 minutes and 1, 2, 4, and 6 hours after dosing