A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01780259
First received: January 28, 2013
Last updated: August 6, 2013
Last verified: August 2013
  Purpose

The primary purpose of the study is to evaluate the pharmacokinetics (what the body does to the medication) of intranasally (through the nose) administered esketamine in healthy participants.


Condition Intervention Phase
Healthy
Drug: Esketamine
Drug: Placebo
Drug: Triazolam
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Maximum plasma concentration during a dosing interval (Cmax) of esketamine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Time to reach the maximum plasma concentration (tmax) of esketamine [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of esketamine [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: Up to 78 days ] [ Designated as safety issue: Yes ]

Enrollment: 58
Study Start Date: December 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Treatment A
Participants will receive 1 spray of esketamine solution in each nostril once (total dose: 28 mg).
Drug: Esketamine
1 spray of 14 percent of esketamine solution (14 mg of esketamine per 100 microlitre) will be administered intranasally by nasal spray pump in each nostril once (Treatment A-total dose: 28 mg), twice with 5 minutes interval (Treatment B-total dose: 56 mg), thrice with 5 minutes interval between each repeated sprays (Treatment C-total dose: 84 mg), thrice with 10 minutes interval between each repeated sprays (Treatment D-total dose: 84 mg) and 4 times with 10 minutes interval between each repeated sprays (Treatment E-total dose: 112 mg). Treatment A, B, C, D will be administered in Cohort 1; Treatment D will be administered in Cohort 2; and Treatment E will be administered in Cohort 3.
Experimental: Cohort 1: Treatment B
Participants will receive 1 spray of esketamine solution in each nostril twice, with 5 minutes interval (total dose: 56 mg).
Drug: Esketamine
1 spray of 14 percent of esketamine solution (14 mg of esketamine per 100 microlitre) will be administered intranasally by nasal spray pump in each nostril once (Treatment A-total dose: 28 mg), twice with 5 minutes interval (Treatment B-total dose: 56 mg), thrice with 5 minutes interval between each repeated sprays (Treatment C-total dose: 84 mg), thrice with 10 minutes interval between each repeated sprays (Treatment D-total dose: 84 mg) and 4 times with 10 minutes interval between each repeated sprays (Treatment E-total dose: 112 mg). Treatment A, B, C, D will be administered in Cohort 1; Treatment D will be administered in Cohort 2; and Treatment E will be administered in Cohort 3.
Experimental: Cohort 1: Treatment C
Participants will receive 1 spray of esketamine solution in each nostril thrice, with 5 minutes interval between each repeated sprays (total dose 84 mg).
Drug: Esketamine
1 spray of 14 percent of esketamine solution (14 mg of esketamine per 100 microlitre) will be administered intranasally by nasal spray pump in each nostril once (Treatment A-total dose: 28 mg), twice with 5 minutes interval (Treatment B-total dose: 56 mg), thrice with 5 minutes interval between each repeated sprays (Treatment C-total dose: 84 mg), thrice with 10 minutes interval between each repeated sprays (Treatment D-total dose: 84 mg) and 4 times with 10 minutes interval between each repeated sprays (Treatment E-total dose: 112 mg). Treatment A, B, C, D will be administered in Cohort 1; Treatment D will be administered in Cohort 2; and Treatment E will be administered in Cohort 3.
Experimental: Cohort 1: Treatment D
Participants will receive 1 spray of esketamine solution in each nostril thrice, with 10 minutes interval between each repeated sprays (total dose 84 mg).
Drug: Esketamine
1 spray of 14 percent of esketamine solution (14 mg of esketamine per 100 microlitre) will be administered intranasally by nasal spray pump in each nostril once (Treatment A-total dose: 28 mg), twice with 5 minutes interval (Treatment B-total dose: 56 mg), thrice with 5 minutes interval between each repeated sprays (Treatment C-total dose: 84 mg), thrice with 10 minutes interval between each repeated sprays (Treatment D-total dose: 84 mg) and 4 times with 10 minutes interval between each repeated sprays (Treatment E-total dose: 112 mg). Treatment A, B, C, D will be administered in Cohort 1; Treatment D will be administered in Cohort 2; and Treatment E will be administered in Cohort 3.
Experimental: Cohort 2: Treatment D
Participants will receive 1 spray of esketamine solution in each nostril thrice, with 10 minutes interval between each repeated sprays (total dose 84 mg).
Drug: Esketamine
1 spray of 14 percent of esketamine solution (14 mg of esketamine per 100 microlitre) will be administered intranasally by nasal spray pump in each nostril once (Treatment A-total dose: 28 mg), twice with 5 minutes interval (Treatment B-total dose: 56 mg), thrice with 5 minutes interval between each repeated sprays (Treatment C-total dose: 84 mg), thrice with 10 minutes interval between each repeated sprays (Treatment D-total dose: 84 mg) and 4 times with 10 minutes interval between each repeated sprays (Treatment E-total dose: 112 mg). Treatment A, B, C, D will be administered in Cohort 1; Treatment D will be administered in Cohort 2; and Treatment E will be administered in Cohort 3.
Experimental: Cohort 3: Treatment E
Participants will receive 1 spray of esketamine solution in each nostril, 4 times with 10 minutes interval between each repeated sprays (total dose: 112 mg). Single dose of oral placebo will be administered 5 minutes before the first intranasal spray of esketamine solution.
Drug: Esketamine
1 spray of 14 percent of esketamine solution (14 mg of esketamine per 100 microlitre) will be administered intranasally by nasal spray pump in each nostril once (Treatment A-total dose: 28 mg), twice with 5 minutes interval (Treatment B-total dose: 56 mg), thrice with 5 minutes interval between each repeated sprays (Treatment C-total dose: 84 mg), thrice with 10 minutes interval between each repeated sprays (Treatment D-total dose: 84 mg) and 4 times with 10 minutes interval between each repeated sprays (Treatment E-total dose: 112 mg). Treatment A, B, C, D will be administered in Cohort 1; Treatment D will be administered in Cohort 2; and Treatment E will be administered in Cohort 3.
Drug: Placebo
Single dose of oral placebo will be administered 5 minutes before the first intranasal spray of esketamine solution in the Treatment E of Cohort 3. Placebo solution (solution of water for injection with denatonium benzoate) will be administered intranasally solution by nasal spray pump in the Treatment F of Cohort 3.
Experimental: Cohort 3: Treatment F
Participants will receive 1 spray of placebo solution in each nostril, 4 times with 10 minutes interval between each repeated sprays (total dose: 112 mg). Single 0.25-mg oral dose of triazolam will be administered 5 minutes before the first intranasal spray of placebo solution.
Drug: Placebo
Single dose of oral placebo will be administered 5 minutes before the first intranasal spray of esketamine solution in the Treatment E of Cohort 3. Placebo solution (solution of water for injection with denatonium benzoate) will be administered intranasally solution by nasal spray pump in the Treatment F of Cohort 3.
Drug: Triazolam
Single 0.25-mg oral dose of triazolam will be administered 5 minutes before the first intranasal spray of placebo solution in the Treatment F of Cohort 3.

Detailed Description:

This is a single-center study with 3 cohorts (groups). Approximately 58 participants will be enrolled in this study. In Cohort 1, approximately 16 participants will be enrolled for up to 78 days and they will receive 4 different single-dose regimens (Treatment A, B, C and D) of intranasal spray of esketamine solution in a crossover manner (participants will be switched from one single-dose regimen to another) and in an open label manner (both the investigator and the participant know the intervention received by the participant). In Cohort 2, approximately 14 participants will be enrolled for up to 35 days and they will receive 1 regimen of intranasal esketamine (Treatment D) in an open label manner. In Cohort 3, approximately 28 participants will be enrolled and they will be randomly assigned to receive either Treatment E (intranasal esketamine spray) or Treatment F (intranasal placebo spray) in a double blind manner (both the investigator and the participant do not know the intervention received by the participant). Safety evaluations will include assessment of adverse events, targeted nasal examinations, laboratory tests, electrocardiogram, physical examination, pulse oximetery, and vital signs.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Blood pressure between 90 and 145 mmHg systolic and no higher than 90 mmHg diastolic
  • A 12-lead electrocardiogram consistent with normal cardiac conduction and function
  • Agree to protocol-defined method of contraception
  • Comfortable with self-administration of intranasal medication

Exclusion Criteria:

  • History of or current clinically significant medical illness including cardiac arrhythmias or other cardiac disease; hematologic disease; coagulation disorders; significant pulmonary disease, including bronchospastic respiratory disease; diabetes mellitus; renal or hepatic insufficiency; thyroid disease; neurologic or psychiatric disease, asthma
  • Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study center
  • Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram at screening or at admission to the study center
  • Known allergy to heparin or history of heparin-induced thrombocytopenia
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01780259

Locations
Belgium
Merksem, Belgium
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01780259     History of Changes
Other Study ID Numbers: CR100942, ESKETINTRD1001, 2012-004374-25
Study First Received: January 28, 2013
Last Updated: August 6, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Janssen Research & Development, LLC:
Healthy
Esketamine
Pharmacokinetics
Intranasal

Additional relevant MeSH terms:
Triazolam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014