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

A Fixed-sequence, Open-label Study to Assess the Effect of Ticlopidine on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Esketamine; Drug: Ticlopidine

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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:

  1. Not of childbearing potential defined as:

     1. 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)
     2. permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy)

  2. Of childbearing potential, heterosexually active, and

     1. practicing a highly effective method of contraception (failure rate of less than [<]1 percent [%] per year when used consistently and correctly)
     2. 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

  1. must be practicing a highly effective method of contraception with his female partner
  2. must use a condom if his partner is pregnant, and
  3. 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

Exclusion Criteria:

• Has a current significant psychiatric disorder including but not limited to psychotic, bipolar, major depressive, or anxiety disorder
• Has a 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 medical conditions that are stable with treatment may be included and should be discussed with the medical monitor before inclusion
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Esketamine + Ticlopidine; 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; 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.; Other Names: JNJ-54135419; Drug: Ticlopidine; Participants will receive 250 mg ticlopidine tablets orally twice daily on Day -9 through Day 1 in Treatment Period 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) as a measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	From signing of the informed consent form (ICF) onwards until the participant's last study-related activity (Approximately up to 8 weeks)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2017
• Primary Completion (Actual): November 27, 2017
• Study Completion (Actual): November 27, 2017

Study Registration Dates

• First Submitted: September 27, 2017
• First Submitted That Met QC Criteria: September 27, 2017
• First Posted (Actual): October 2, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Neurotransmitter Agents; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents; Cytochrome P-450 CYP2C19 Inhibitors; Esketamine; Ticlopidine
• Other Study ID Numbers: CR108377; 54135419TRD1020 (Other Identifier: Janssen Research & Development, LLC); 2017-003174-14 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes