A Study to Assess the Effect of Ticlopidine on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants

NCT03298906 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR10837754135419TRD10202017-003174-14
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effects of ticlopidine on the pharmacokinetics (PK) of intranasally administered esketamine.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax) of Esketamine

  The Cmax is the maximum observed plasma concentration.

  Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose

• 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 area under the plasma concentration time curve from time zero to last quantifiable time; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

  Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose

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

  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable concentration.

  Day 1: 0 (pre-dose), 7, 12, 20, 30, 40, 50 minutes; 1, 1.25, 1.5, 2, 3, 4, 6, 9, 12, 18, 24 and 30 hours post-dose

Secondary Outcomes (1)

• Number of Participants with Adverse Events (AEs) as a measure of Safety and Tolerability

  From signing of the informed consent form (ICF) onwards until the participant's last study-related activity (Approximately up to 8 weeks)

Study Arms (1)

Esketamine + Ticlopidine

EXPERIMENTAL

Participants will self-administer one 14 milligram (mg) spray of intranasal esketamine into each nostril at Time 0 and again 5 minutes later on Day 1, a total dose of 56 mg (Treatment A) in Treatment Period 1. After that participants will receive 250 mg of ticlopidine tablets orally twice daily on Day -9 through Day 1, and will self-administer one 14 mg spray of intranasal esketamine into each nostril at Time 0 and again 5 minutes later in the morning of Day 1, a total dose of 56 mg (Treatment B) in Treatment Period 2. A washout period of greater than or equal to (\>=)10 days will separate the esketamine self-administrations between 2 treatment periods.

Drug: Esketamine; Drug: Ticlopidine

Interventions

Esketamine DRUG

Participants will self-administer one intranasal spray of 14 mg esketamine at Time 0 and again 5 minutes later on Day 1, a total dose of 56 mg in Treatment Period 1 and 2.

Also known as: JNJ-54135419

Esketamine + Ticlopidine

Ticlopidine DRUG

Participants will receive 250 mg ticlopidine tablets orally twice daily on Day -9 through Day 1 in Treatment Period 2.

Esketamine + Ticlopidine

Eligibility Criteria

• Age: 18 Years - 58 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
• A woman must be either:
• Not of childbearing potential defined as:
• postmenopausal (it is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone \[FSH\] level \[greater than {\>}40 International Unit per Liter {IU/L} or milliinternational Unit per milliliter {mIU/mL}\] in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy, however in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient)
• permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy)
• Of childbearing potential, heterosexually active, and
• practicing a highly effective method of contraception (failure rate of less than \[\<\]1 percent \[%\] per year when used consistently and correctly)
• agree to remain on a highly effective method throughout the study and for at least 6 weeks after the last dose of study drug
• For women, must have a negative serum Beta- human chorionic gonadotropin (Beta-hCG) pregnancy test at screening
• During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of intranasal study medication, a man who is sexually active with a woman of childbearing potential
• must be practicing a highly effective method of contraception with his female partner
• must use a condom if his partner is pregnant, and
• must agree not to donate sperm
• Have a creatinine clearance greater than or equal to (\>=) 60 milliliter per minute (mL/min) (calculated using the Cockcroft-Gault formula) at screening

You may not qualify if:

• Has a current significant psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder
• Has clinically significant abnormal values for hematology, serum chemistry, or urinalysis at screening as deemed appropriate by the investigator
• Has any contraindication to the use of ticlopidine, ketamine, or esketamine per prescribing information
• Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

Esketamine; Ticlopidine

Intervention Hierarchy (Ancestors)

Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 2, 2017
• Study Start: September 26, 2017
• Primary Completion: November 27, 2017
• Study Completion: November 27, 2017
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

BE (1)