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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02094378
• Other study ID #: CR103823
• Secondary ID: ESKETINTRD100520
• Status: Completed
• Phase: Phase 1
• First received: March 20, 2014
• Last updated: October 15, 2014
• Start date: June 2014
• Est. completion date: August 2014

Study information

• Verified date: October 2014
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 49 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Esketamine
84 mg esketamine administered intranasally
• Placebo
Placebo administered intranasally

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Primary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No