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Pharmacokinetic, Safety, and Tolerability Study of Intranasally Administered Esketamine in Elderly Japanese, and Healthy Younger Adult Japanese Subjects

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ClinicalTrials.gov Identifier: NCT02857777
Recruitment Status : Completed
First Posted : August 5, 2016
Last Update Posted : March 14, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to compare the pharmacokinetics, safety, and tolerability of intranasally administered esketamine in elderly Japanese subjects and healthy younger adult Japanese subjects.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Ascending Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Elderly (>=65 Years of Age) Japanese, and Healthy Younger Adult Japanese Subjects (20 to 55 Years of Age, Inclusive)
Actual Study Start Date : August 9, 2016
Actual Primary Completion Date : January 27, 2017
Actual Study Completion Date : January 27, 2017

Arm Intervention/treatment
Experimental: Cohort 1: Japanese elderly subjects (Esketamine)
Subjects will receive Treatment A (28 milligram [mg] of esketamine, administered as 1*14 mg spray of esketamine in each nostril at Time 0) in Period 1, Treatment B (56 mg of esketamine, administered as 1*14 mg spray of esketamine in each nostril at Time 0 and 5 minutes) in Period 2 and then Treatment C (84 mg of esketamine, administered as 1*14 mg spray of esketamine in each nostril at Time 0, 5, and 10 minutes) in Period 3. A washout period of 5 to 14 days will separate each intranasal esketamine treatment regimen.
Drug: Esketamine
Subjects will self-administer intranasal esketamine as per the treatment regimen.

Active Comparator: Cohort 2: Japanese healthy subjects (Esketamine)
Subjects will receive Treatment A in Period 1, Treatment B in Period 2 and then Treatment C in Period 3. A washout period of 5 to 14 days will separate each intranasal esketamine treatment regimen.
Drug: Esketamine
Subjects will self-administer intranasal esketamine as per the treatment regimen.




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

  2. Area Under the Plasma Concentration-Time Curve From Time Zero to 12 hours (AUC [0-12]) [ Time Frame: up to Day 2 ]
    The AUC (0-12) is the area under the plasma concentration-time curve from time zero to 12 hours, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

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

  4. 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(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

  5. Terminal Half-Life(t[1/2]) [ Time Frame: up to Day 2 ]
    Terminal half-life (t[(1/2]) is defined as 0.693/Lambda(z).

  6. Lambda(z) [ Time Frame: up to Day 2 ]
    Lambda(z) is the 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.

  7. Number of subjects with Adverse Events (AEs) as a measure of safety and tolerability [ Time Frame: Screening up to Follow-up (63 days) ]


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A) Cohort 1: Be a Japanese man or woman greater than or equal to (>=) 65 years of age with at least 4 subjects >= 70 years of age, who was born in Japan, who has resided outside of Japan for >= 10 years, with parents and maternal and paternal grandparents who are of Japanese ethnicity. Subjects must be either healthy or present with stable, well-controlled, chronic conditions which frequently occur in the elderly, such as: Hyperlipidemia,Controlled hypertension, Impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes mellitus controlled with diet, and/or metformin monotherapy, dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy or a combination of metformin and DPP-4 inhibitor, who have glycated hemoglobin (HbA1c) levels <8 percent (%), Degenerative joint disorders and osteoporosis; B) Cohort 2: Be a healthy Japanese man or woman 20 to 55 years of age, inclusive, who was born in Japan, who has resided outside of Japan for >= 10 years, and has parents and maternal and paternal grandparents who are of Japanese ethnicity. Each subject will be matched to an elderly subject in Cohort 1 by gender and body weight (+/- 20%) using data collected during Screening
  • Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
  • Willing to adhere to the prohibitions and restrictions specified in this protocol
  • Cohort 2: If a woman, must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening and a negative urine pregnancy test on Day -1 of the treatment period. Women using contraceptives must agree to use an additional birth control method during the study and for 1 month after receiving the last dose of study drug
  • If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction

Exclusion Criteria:

  • Current significant psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder
  • 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), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the subject or that could interfere with the interpretation of the study results. Elderly subjects in Cohort 1 with stable, well-controlled, chronic conditions which frequently occur in the elderly as outlined in Inclusion Criteria 1 will be permitted to participate in the study
  • 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 before the first study drug administration as deemed appropriate by the investigator
  • History of moderate or severe use disorder according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria within 1 year before screening or positive test result(s) for alcohol and/or drugs of abuse (such as barbiturates, opiates, cocaine, cannabinoids, amphetamines, and benzodiazepines) at screening and Day -1 of the treatment period

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): NCT02857777


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: NCT02857777     History of Changes
Other Study ID Numbers: CR108213
54135419TRD1018 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 5, 2016    Key Record Dates
Last Update Posted: March 14, 2017
Last Verified: March 2017