Pharmacokinetic Study of Intranasal Esketamine and Its Effects on the Pharmacokinetics of Orally-Administered Midazolam and Bupropion in Healthy Participants

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Bupropion; Drug: Esketamine; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT02568176

ESKETINTRD1010 (Other Identifier)

CR108043

2015-002654-13 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 71 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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71 participants in 2 patient groups

Cohort 1

Experimental group

Description:

Participants will receive single oral dose of midazolam 6 milligram (mg) on Day 1 and 17. Participants will self-administer esketamine intranasally thrice per day on morning of Day 2, 5, 9, 12 and 16 (84 mg).

Treatment:

Drug: Midazolam

Drug: Esketamine

Cohort 2

Experimental group

Description:

Participants will receive single oral dose of bupropion 150 mg on Day 1 and 19. Participants will self-administer esketamine intranasally thrice per day on morning of Day 4, 7, 11, 14 and 18 (84 mg).

Treatment:

Drug: Esketamine

Drug: Bupropion