Healthy
Conditions
Keywords
Healthy, Pharmacokinetics, Esketamine, JNJ-54135419, Midazolam, Bupropion
Brief summary
The primary purpose of this study is to evaluate the induction potential of repeated administration of intranasal esketamine on cytochrome P450 (CYP) 3A4 and CYP2B6 activity in healthy participants using orally administered midazolam and bupropion as probes, respectively and to evaluate the pharmacokinetics of esketamine after a single dose and repeated administration.
Detailed description
This is a parallel group, single-center, repeat-dose, fixed-sequence, open-label (all people know the identity of the intervention), study. The effects of repeated administration of intranasal esketamine on the pharmacokinetics of midazolam and bupropion will be evaluated in Cohort 1 and Cohort 2, respectively. Participants in Cohort 1 will receive a single oral dose of midazolam in the morning of Day 1 and Day 17. Participants in Cohort 2 will receive a single oral dose of bupropion in the morning of Day 1 and Day 19. In Cohort 1 and 2 participants will self-administer 5 doses of intranasal esketamine over a 15-day period. The duration of study, from the Screening Phase through Follow-up, is up to 51 days and 54 days for Cohort 1 and Cohort 2, respectively. Blood samples for participants in Cohort 1 will be collected for up to 24 hours after dosing on Days 1 and 17 (midazolam) and for up to 24 hours on Days 2 and 16 (esketamine); For participants in Cohort 2, blood and urine samples for assessment of bupropion pharmacokinetics will be collected for up to 72 hours after dosing on Day 1 and Day 19. Participants' safety will be monitored throughout the study.
Interventions
DRUGMidazolam
Single oral dose of midazolam 6 mg Day 1 and Day 17.
DRUGEsketamine
Intranasal esketamine will be self-administered 5 times during 15 days.
DRUGBupropion
Single oral dose of bupropion 150 mg on Day 1 and 19.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Be a man or woman of non-Asian origin 18 to 55 years of age, inclusive * 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 * A woman of child-bearing potential, must have a negative serum β-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 * A man who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the investigator (eg, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug * Comfortable with self-administration of intranasal medication and able to follow instructions provided
Exclusion criteria
* Clinically significant abnormal values for hematology, clinical chemistry (particularly potassium or magnesium levels below the normal laboratory range), or urinalysis at Screening or at admission to the study center (Day -1) as deemed appropriate by the investigator * Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or at admission to the study center (Day -1) as deemed appropriate by the investigator * Use of any prescription or non-prescription medication (including vitamins and herbal supplements), except for paracetamol, contraceptives, and hormonal replacement therapy, within 14 days before the first dose of the study drug is scheduled until completion of the study * Has used nasal tobacco powder (snuff) regularly within the past year. * Has a nasal piercing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ae metabolite to parent ratio (MPR Ae) | up to Day 19 for Cohort 2 | Ae metabolite to parent ratio, and corrected for molecular weight if necessary. |
| Maximum Plasma Concentration (Cmax) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 2 | The Cmax is the maximum plasma concentration. |
| Time to reach maximum concentration (tmax) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 2 | Time to reach the maximum observed plasma concentration. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 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. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 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. |
| Terminal Half-Life(t[1/2]) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 2 | Terminal half-life (t\[(1/2\]) is defined as 0.693/Lambda(z). |
| Area Under the Plasma Concentration-Time Curve From Time Zero to 12 hours (AUC [0-12]) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 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. |
| Cmax metabolite to parent ratio (MPR Cmax) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 2 | Cmax metabolite to parent ratio, and corrected for molecular weight if necessary. |
| AUC(last) metabolite to parent ratio (MPR AUC[last]) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 2 | AUC(last) metabolite to parent ratio, and corrected for molecular weight if necessary. |
| AUC (infinity) metabolite to parent ratio (MPR AUC [infinity]) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 2 | AUC (infinity) metabolite to parent ratio, and corrected for molecular weight if necessary. |
| Amount of Drug excreted in Urine (Ae) | up to Day 17 for Cohort 1; up to Day 19 for Cohort 2 | Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals. |
| Percentage of Drug dose excreted into urine | up to Day 19 for Cohort 2 | Total amount excreted into the urine, expressed as a percentage of the administered dose, calculated as (Ae/dose)\*100, and corrected for molecular weight if necessary. |
| Renal clearance | up to Day 19 for Cohort 2 | Renal clearance calculated as Ae/AUC (infinity). |
| Formation Clearance | up to Day 19 for Cohort 2 | Formation clearance of drug, calculated as Ae of hydroxybupropion/AUC(infinity) of bupropion, and corrected for molecular weight if necessary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Day 51 for Cohort 1; Baseline up to Day 54 Cohort 2 | An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
Countries
Belgium
Outcome results
None listed