A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants
This study is currently recruiting participants.
Verified April 2013 by Janssen Research & Development, LLC
Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01780259
First received: January 28, 2013
Last updated: April 29, 2013
Last verified: April 2013
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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 ]
| Estimated Enrollment: | 58 |
| Study Start Date: | December 2012 |
| Estimated Study Completion Date: | April 2013 |
| Estimated Primary Completion Date: | April 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
Contacts
| Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: | JNJ.CT@sylogent.com |
Locations
| Belgium | |
| Recruiting | |
| Merksem, Belgium | |
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
More Information
Additional 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: | April 29, 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 May 19, 2013