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

• Register: ClinicalTrials.gov
• Last refreshed on: 6 October 2015
• Main ID: NCT02343289
• Date of registration: 15/01/2015
• Prospective Registration: No
• Primary sponsor: Janssen Research & Development, LLC
• Public title: 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
• Scientific title: An Open-Label Study to Evaluate the Absolute Bioavailability of Intranasal and Oral Esketamine and the Effects of Clarithromycin on the Pharmacokinetics of Intranasal Esketamine in Healthy Subjects
• Date of first enrolment: January 2015
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02343289
• Study type: Interventional
• Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Belgium

Contacts

• Name: Janssen Research & Development, LLC Clinical Trial
• Affiliation: Janssen Research & Development, LLC

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Healthy

Intervention(s)

Drug: Clarithromycin

Drug: Esketamine

Primary Outcome(s)

Absolute Bioavailability (Fabs) of Esketamine [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]

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [Time Frame: Throughout the duration of study (approximately up to 98 days)]

Rate Constant (Lambda[z]) of Esketamine [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 [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 [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 [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]

Elimination Half-life (t1/2) of Esketamine [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]

Maximum Plasma Concentration (Cmax) of Esketamine [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]

Relative Bioavailability of Esketamine (Frel) [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]

Percentage of Area Under the Plasma Concentration-time Curve Obtained by Extrapolation (%AUC [infinity,ex]) of Esketamine [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 [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]

Secondary ID(s)

CR106240

ESKETINTRD1009

2014-004055-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors