A Study to Evaluate the Absolute Bioavailability of Intranasal and Oral Esketamine and the Effects of Clarithromycin on the Pharmacokinetics of Intranasal Esketamine in Healthy Participants

Janssen Research & Development, LLC18 enrolled

Overview

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of esketamine administered by the intranasal (administered through the nose) and oral routes and to evaluate the effects of clarithromycin on the pharmacokinetics of intranasally administered esketamine.

This is a single-center, 4-period, fixed-sequence, open-label study. The study consists of Screening Period (Days -21 to -2), Open-label Treatment Period 1, 2, 3, 4 and End of Study (9 to 13 days after final dose or at Early Withdrawal). The total duration of study will be up to 98 days. For all 4 periods, the participants will be admitted into the study center on Day -1 of each treatment period and receive a 28 milligram (mg) (intravenous) or 84 mg (oral and intranasal) esketamine dose regimen on Day 1 of each period in a fixed sequence. Participants will also receive 500 mg of clarithromycin in period 4. Blood samples will be collected to evaluate the pharmacokinetic parameters. Participants' safety will be monitored throughout the study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

EsketamineDRUG

28 mg of esketamine as a single, 40-minute, intravenous infusion on Day 1 of Period 1, 84 mg of esketamine solution as a single, oral dose on Day 1 of Period 2, 84 mg of intranasal esketamine on Day 1 of Period 3 and on Day 1 of Period 4.

ClarithromycinDRUG

500 mg of clarithromycin twice daily on Days -3, -2, -1, 1, and 2 of Period 4.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * For women of childbearing potential, must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening; and a negative urine pregnancy test on Day -1 of Period 1 * If a man, must agree to use an adequate contraception method as deemed appropriate by the investigator (example, 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 * Participants with body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m\^2) (inclusive), and body weight not less than 50 kg * Participants with blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic * Participants should be comfortable with self-administration of intranasal medication and able to follow instructions provided Exclusion Criteria: * Participants diagnosed with a psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder * Participants with 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, renal or hepatic insufficiency, thyroid disease, neurologic disease, infection, hypertension or vascular disorders, kidney or urinary tract disturbances, sleep apnea, myasthenia gravis, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results * Participants with 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 of Period 1) as deemed appropriate by the investigator * Participants with clinically significant abnormal physical examination and vital signs at screening or at admission to the study center (Day -1 of Period 1) as deemed appropriate by the investigator * Participants with history of drug or alcohol abuse disorder within the past 1 year, or a reason to believe a participant has such a history

Locations (1)

Unnamed facility

Merksem, Belgium

Outcomes

Primary Outcomes

Maximum Plasma Concentration (Cmax) of Esketamine

The Cmax is the maximum plasma concentration.

Time frame: Pre-dose, 0.25, 0.33, 0.5, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18 hour (hr) post-dose on Day 1; 24, 36 hr post-dose on Day 2; 48 hr post-dose on Day 3 in all periods

Time to Reach Maximum Plasma Concentration (Tmax) of Esketamine

The Tmax is time to reach the maximum plasma concentration.

Time frame: Pre-dose, 0.25, 0.33, 0.5, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18 hour (hr) post-dose on Day 1; 24, 36 hr post-dose on Day 2; 48 hr post-dose on Day 3 in all periods

Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC12h) of Esketamine

The (AUC12h) is the area under the plasma concentration-time curve from time 0 to 12 hours Post-dose.

Time frame: Pre-dose, 0.25, 0.33, 0.5, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hour (hr) post-dose on Day 1 in all periods

Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Esketamine

The (AUC \[0-last\]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.

Time frame: Pre-dose, 0.25, 0.33, 0.5, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18 hour (hr) post-dose on Day 1; 24, 36 hr post-dose on Day 2; 48 hr post-dose on Day 3 in all periods

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Esketamine

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.

Time frame: Pre-dose, 0.25, 0.33, 0.5, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18 hour (hr) post-dose on Day 1; 24, 36 hr post-dose on Day 2; 48 hr post-dose on Day 3 in all periods

Data from ClinicalTrials.gov

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