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Pharmacokinetic, Safety, and Tolerability Study of Intranasally Administered Esketamine in Healthy Han Chinese, Korean, Japanese, and Caucasian Participants and the Effects of Rifampin on the Pharmacokinetics of Intranasally Administered Esketamine

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ClinicalTrials.gov Identifier: NCT02846519
Recruitment Status : Completed
First Posted : July 27, 2016
Last Update Posted : October 18, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the pharmacokinetics of intranasally administered esketamine in healthy Han Chinese, Korean, Japanese, and Caucasian participants and to evaluate the effects of rifampin on the pharmacokinetics of intranasally administered esketamine in healthy Caucasian participants.

Condition or disease Intervention/treatment Phase
Healthy Drug: Esketamine Drug: Rifampin Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Han Chinese, Korean, Japanese, and Caucasian Subjects and the Effects of Rifampin on the Pharmacokinetics of Intranasally Administered Esketamine
Actual Study Start Date : February 26, 2016
Actual Primary Completion Date : May 28, 2016
Actual Study Completion Date : May 28, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Rifampin
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Esketamine
Participants in Cohort 1 (Han Chinese participants), Cohort 2 (Korean participants) and Cohort 3 (Japanese participants ) will receive 100-microliter (mcL) spray of 14 percent (%) esketamine solution (14 milligram [mg]) into each nostril at Time 0 and 5 minutes later for a total dose of 56 milligram (mg) in Period 1.
Drug: Esketamine
100-mcL spray of 14% esketamine solution (14 mg) for a total dose of 56 mg.
Experimental: Esketamine+Rifampin
Participants in Cohort 4 (Caucasian participants) will receive a 56-mg intranasal esketamine dose regimen on Day 1 in treatment period 1 followed by rifampin from Day -6 to Day -1 of treatment Period 2 and followed by 56-mg intranasal esketamine dose regimen on Day 1 in treatment period 2.
Drug: Esketamine
100-mcL spray of 14% esketamine solution (14 mg) for a total dose of 56 mg.
Drug: Rifampin
2 capsules (300 mg each) of rifampin.



Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Day 2 ]
    The Cmax is the maximum observed plasma concentration.

  2. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Up to Day 2 ]
    The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.

  3. Time to Last Observed Quantifiable Plasma Concentration (Tlast) [ Time Frame: Up to Day 2 ]
    The Tlast is the time to last observed quantifiable plasma concentration.

  4. Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC12h) [ Time Frame: Up to Day 2 ]
    The (AUC12h) is the area under the plasma concentration-time curve from time 0 to 12 hours Post-dose.

  5. Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) [ Time Frame: Up to Day 2 ]
    The AUC (0-last) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.

  6. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) [ Time Frame: Up to Day 2 ]
    The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

  7. Elimination Half-life (t1/2) [ Time Frame: Up to Day 2 ]
    Elimination half-life (t [1/2]) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).

  8. Rate Constant (Lambda[z]) [ Time Frame: Up to Day 2 ]
    Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability [ Time Frame: Up to Follow-up (45 days) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • For Cohort 1: healthy Han Chinese participants 20 to 55 years of age, inclusive, who have resided outside of China for no more than 10 years and have parents and maternal and paternal grandparents who are of Han Chinese ethnicity For Cohort 2: healthy Korean participants 20 to 55 years of age, inclusive, who have resided outside of Korea for no more than 10 years and have parents and maternal and paternal grandparents who are of Korean ethnicity For Cohort 3: healthy Japanese participants 20 to 55 years of age, inclusive, who have resided outside of Japan for no more than 10 years and have parents and maternal and paternal grandparents who are of Japanese ethnicity For Cohort 4: healthy Caucasian participants 20 to 55 years of age, inclusive Participants must be within +/-7 years and +/-20 percent (%) of the combined mean age and mean body weight at Screening, respectively, of Cohort 1, Cohort 2, and Cohort 3
  • Body mass index (BMI; weight [kilogram]/height^2 [m]^2) between 18 and 30 kilogram per meter square (kg/m^2), inclusive, and a body weight not less than 47 kilogram (kg)
  • If a woman, must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening
  • If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 1 month after receiving the last dose of study drug
  • Creatinine clearance more than equal to (>=)80 milliliters per minute (mL/min) based on Cockroft-Gault equation

Exclusion Criteria:

  • Current significant psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder
  • Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening or Day -1 of Period 1 as deemed appropriate by the investigator
  • Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or Day -1 of Period 1 as deemed appropriate by the investigator
  • History of drug or alcohol abuse disorder within the past 1 year, or a reason to believe a participant has such a history
  • Regular use of intranasal tobacco powder within the past 1 year, or a reason to believe a participant has such a history

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02846519


Locations
United States, California
Cypress, California, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02846519     History of Changes
Other Study ID Numbers: CR108128
ESKETINTRD1008 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: July 27, 2016    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Rifampin
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers