ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03298906
Recruitment Status : Completed
First Posted : October 2, 2017
Last Update Posted : December 20, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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

Condition or disease Intervention/treatment Phase
Healthy Drug: Esketamine Drug: Ticlopidine Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: 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
Actual Study Start Date : September 26, 2017
Actual Primary Completion Date : November 27, 2017
Actual Study Completion Date : November 27, 2017

Resource links provided by the National Library of Medicine


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 Name: JNJ-54135419

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




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Esketamine [ Time Frame: 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 ]
    The Cmax is the maximum observed plasma concentration.

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

  3. Area Under the Plasma Concentration-time Curve From Time Zero to time of Last Quantifiable Concentration (AUC [0-last]) of Esketamine [ Time Frame: 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 ]
    The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable concentration.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) as a measure of Safety and Tolerability [ Time Frame: From signing of the informed consent form (ICF) onwards until the participant's last study-related activity (Approximately up to 8 weeks) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 58 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298906


Locations
Belgium
Clinical Pharmacology Unit
Merksem, Belgium, 2170
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03298906     History of Changes
Other Study ID Numbers: CR108377
54135419TRD1020 ( Other Identifier: Janssen Research & Development, LLC )
2017-003174-14 ( EudraCT Number )
First Posted: October 2, 2017    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 2017

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

Additional relevant MeSH terms:
Ticlopidine
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors