A Study to Evaluate the Effect of Intranasal Esketamine on Cognitive Functioning in Healthy Subjects

NCT02094378 | Completed Phase 1 DMC

• 3 other identifiers: CR103823ESKETINTRD10052014-000468-16
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Healthy; Esketamine; Cognitive functioning

Outcome Measures

Primary Outcomes (3)

• 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).

  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).

  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).

  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 (3)

• The concentration of esketamine and noresketamine from time zero to the last observable concentration (AUClast)

  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

  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

  Day 1 at 0, 10, and 40 minutes and 1, 2, 4, and 6 hours after dosing

Study Arms (2)

Esketamine-Placebo

EXPERIMENTAL

Participants assigned to treatment sequence 1 will receive 84 mg esketamine intranasally on Day 1 of Period 1 and then receive placebo intranasally on Day 1 in Period 2. Periods 1 and 2 will be separated by 7 days.

Drug: Esketamine; Drug: Placebo

Placebo-Esketamine

PLACEBO COMPARATOR

Participants assigned to treatment sequence 2 will receive placebo intranasally on Day 1 of Period 1 and then receive 84 mg esketamine intranasally on Day 1 in Period 2. Periods 1 and 2 will be separated by 7 days.

Drug: Esketamine; Drug: Placebo

Interventions

Esketamine DRUG

84 mg esketamine administered intranasally

Esketamine-Placebo; Placebo-Esketamine

Placebo DRUG

Placebo administered intranasally

Esketamine-Placebo; Placebo-Esketamine

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Leiden, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 29392371 DERIVED

MeSH Terms

Interventions

Esketamine

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 21, 2014
• Study Start: June 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 16, 2014

Record last verified: 2014-10

Locations

NL (1)