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

NCT01980303 | Completed Phase 1

• 2 other identifiers: CR101101ESKETINTRD1002
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this Phase 1 study is to characterize the pharmacokinetic profile (what the body does to the medication) of esketamine when given by the intranasal route (through the nose) to healthy adult Japanese and Caucasian participants.

Conditions

Healthy Volunteers

Keywords

Healthy; Japanese; Caucasian; Anesthetics; Intranasal; Esketamine; Pharmacokinetics

Outcome Measures

Primary Outcomes (5)

• Maximum plasma concentration during a dosing interval (Cmax) of esketamine and noresketamine

  Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours

• Time to reach the maximum plasma concentration (tmax) of esketamine and noresketamine

  Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours

• Area under the plasma concentration-time curve from Time 0 to time of the last quantifiable concentration of esketamine and noresketamine

  Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours

• Elimination half-life of esketamine and noreskatamine

  Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours

• Area under the plasma concentration-time curve from time 0 to infinite time in which Clast is the last observed quantifiable concentration of esketamine and noresketamine

  Predose, 7 minutes, 12 minutes, 22 minutes, 32 minutes, 40 minutes, 50 minutes, 1 hour, 1.25 hours, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours

Secondary Outcomes (1)

• The number of volunteers who experience adverse events as a measure of safety and tolerability.

  Up to 71 days

Study Arms (6)

Cohort 1: Treatment A

EXPERIMENTAL

Japanese participants will receive 1 spray of esketamine solution in each nostril (total dose: 28 mg).

Drug: Esketamine

Cohort 1: Treatment B

EXPERIMENTAL

Japanese participants will receive 1 spray of esketamine solution in each nostril at time 0 and 5 minutes (total dose: 56 mg).

Drug: Esketamine

Cohort 1: Treatment C

EXPERIMENTAL

Japanese participants will receive 1 spray of esketamine solution in each nostril at time 0, 5, and 10 minutes (total dose: 84 mg).

Drug: Esketamine

Cohort 2: Treatment A

EXPERIMENTAL

Caucasian participants will receive 1 spray of esketamine solution in each nostril (total dose: 28 mg).

Drug: Esketamine

Cohort 2: Treatment B

EXPERIMENTAL

Caucasian participants will receive 1 spray of esketamine solution in each nostril at time 0 and 5 minutes (total dose: 56 mg).

Drug: Esketamine

Cohort 2: Treatment C

EXPERIMENTAL

Caucasian participants will receive 1 spray of esketamine solution in each nostril at time 0, 5 and 10 minutes (total dose: 84 mg).

Drug: Esketamine

Interventions

Esketamine DRUG

Fourteen percent esketamine solution (14 mg of esketamine per 100 microliter) will be administered intranasally by nasal spray pump.

Cohort 1: Treatment A; Cohort 1: Treatment B; Cohort 1: Treatment C; Cohort 2: Treatment A; Cohort 2: Treatment B; Cohort 2: Treatment C

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Cypress, California, United States

Location

Related Publications (1)

• Perez-Ruixo C, Rossenu S, Zannikos P, Nandy P, Singh J, Drevets WC, Perez-Ruixo JJ. Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. Clin Pharmacokinet. 2021 Apr;60(4):501-516. doi: 10.1007/s40262-020-00953-4. Epub 2020 Oct 31.

  PMID: 33128208 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: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2013
• First Posted: November 8, 2013
• Study Start: November 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 28, 2014

Record last verified: 2014-01

Locations

US (1)