Clinical trial NCT02094378: A Study to Evaluate the Effect of Intranasal Esketamine on Cognitive Functioning in Healthy Subjects
Official title: A Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study to Evaluate the Effect of Intranasal Esketamine on Cognitive Functioning in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Esketamine
Cognitive functioning
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-03-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the cognitive effects associated with administration of intranasal esketamine 84 mg.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) (weight \[kg\]/height\[m2\]) between 18 and 30 kg/m2 (inclusive), and body weight not less than 45 kg
* Blood pressure (after the subject is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic at Screening and predose on Day 1 of Period 1
* A 12-lead ECG consistent with normal cardiac conduction and function at Screening and predose on Day 1 of Period 1
* Comfortable with self-administration of intranasal medication and able to follow instructions provided
* Non-smoker for at least 6 months before first study drug administration

Exclusion Criteria:

* Subject has clinically significant liver or renal insufficiency; cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances. A significant primary sleep disorder is exclusionary
* Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or on Day 1 of Period 1, as deemed appropriate by the investigator
* Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at screening or on Day 1 of Period 1, as deemed appropriate by the investigator
* Anatomical or medical conditions that may impede delivery or absorption of study medication (e.g., undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; or signs and symptoms of rhinitis predose on Day 1 of Period 1)
* 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, and at times has facial pain, headaches, and postnasal drip

Primary outcomes:
measure: Change from baseline in cognitive functioning measured by the The Cogstate® Computerized Battery
timeFrame: On Day 1 at -1 hour, 40 minutes, and at 2, 4, and 6 hours after dosing (or at the end of treatment)
measure: Change from baseline in cognitive functioning measured by the Karolinska Sleepiness Scale (KSS)
timeFrame: On day 1 at -1 hour, 40 minutes, and at 2, 4, and 6 hours after dosing (or at the end of treatment)
measure: Change from baseline in cognitive functioning measured by the mental effort scale
timeFrame: On Day 1 at -1 hour, 40 minutes, and at 2, 4, and 6 hours after dosing (or at the end of treatment)
Secondary outcomes:
measure: The concentration of esketamine and noresketamine from time zero to the last observable concentration (AUClast)
timeFrame: Day 1 at 0, 10, and 40 minutes and 1, 2, and 4 hours after dosing
measure: The maximum plasma concentration (Cmax) of esketamine and noresketamine
timeFrame: Day 1 at 0,10, and 40 minutes and at 1, 2, 4, and 6 hours after dosing
measure: Time to Maximum Plasma Concentration (Tmax) of esketamine and noresketamine
timeFrame: Day 1 at 0, 10, and 40 minutes and 1, 2, 4, and 6 hours after dosing
Other outcomes:
Locations:
city: Leiden
country: Netherlands
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Morrison RL, Fedgchin M, Singh J, Van Gerven J, Zuiker R, Lim KS, van der Ark P, Wajs E, Xi L, Zannikos P, Drevets WC. Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study. Psychopharmacology (Berl). 2018 Apr;235(4):1107-1119. doi: 10.1007/s00213-018-4828-5. Epub 2018 Feb 1.