A Study to Evaluate the Effects of Esketamine on Cardiac Repolarization in Healthy Participants

April 10, 2018 updated by: Janssen Research & Development, LLC

A Randomized, Double-Blind (Periods 1 to 3), Placebo- and Positive-Controlled, Single Dose, 4-Period, Crossover Study to Evaluate the Effects of Esketamine on Cardiac Repolarization in Healthy Subjects

The purpose of the study is to assess the effects of esketamine on QT/QTc intervals and electrocardiogram (ECG) morphology at therapeutic exposures of esketamine and noresketamine (intranasal administration) and supratherapeutic exposures of esketamine (intravenous administration) in healthy adults.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized (study medication assigned to participants by chance), placebo- and positive-controlled, double-blind (Periods 1 to 3), and open-label (Period 4), single-dose, crossover study in up to 60 healthy adults. The study has a Screening Phase and a Treatment Phase. Participants will be randomly assigned to 1 of 6 treatment sequence groups and will receive the 4 treatments (1 treatment per period); Treatment A (intravenous placebo, Intranasal placebo and Oral placebo tablet matched to the moxifloxacin tablet), Treatment B (intravenous placebo, 84 milligram (mg) of intranasal esketamine as 4 devices, each with 28 mg esketamine and Oral placebo tablet matched to the moxifloxacin tablet), Treatment C (intravenous placebo, Intranasal placebo and 400 mg oral moxifloxacin tablet) and Treatment D (0.8 milligram per kilogram of intravenous esketamine, Intranasal placebo and Oral placebo tablet matched to the moxifloxacin tablet ). The first 3 periods will be double-blinded and the fourth period will be open-label. Periods 1, 2, 3, and 4 will be separated by 5 to 7 days. Primarily the effects of esketamine on QT/QTc intervals and electrocardiogram (ECG) morphology will be evaluated. Safety of the participants will be monitored throughout the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study
  • Body mass index (BMI) between 18 and 30 kilogram (kg)/meter square ([m]^2) (inclusive), and body weight not less than 50 kilogram (kg)
  • Women using oral contraceptives must agree to use an additional birth control method during the study and for 1 month after receiving the last dose of study drug or until after the next menstrual period
  • A woman of child-bearing 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 the first treatment period
  • 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

Exclusion Criteria:

  • Participant has a current diagnosis of psychotic disorder or major depressive disorder (MDD) with psychosis, bipolar or related disorders, intellectual disability, borderline personality disorder, or antisocial personality disorder
  • Clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, gastrointestinal disease, hypertension, vascular disorders, 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
  • History of additional risk factors for torsade de pointes or the presence of a family history of Short QT Syndrome, Long QT Syndrome, sudden unexplained death at a young age (less than/equal to 40 years), drowning or sudden infant death syndrome in a first degree relative (that is, biological parent, sibling, or child)
  • Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at Screening or at admission to the study center for the first treatment period as deemed appropriate by the investigator. Electrolytes (potassium, magnesium, calcium) should be within the reference range of the laboratory
  • Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or at admission to the study center for the first treatment period as deemed appropriate by the investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sequence 1
Participants will receive Treatment A (intravenous placebo, Intranasal placebo and Oral placebo tablet matched to the moxifloxacin tablet) on Day 1 of period 1, Treatment B (intravenous placebo, 84 milligram (mg) of intranasal esketamine and Oral placebo tablet matched to the moxifloxacin tablet) on Day 1 of period 2, Treatment C (intravenous placebo, Intranasal placebo and 400 mg oral moxifloxacin tablet) on Day 1 of period 3, Treatment D (0.8 milligram per kilogram of intravenous esketamine, Intranasal placebo and Oral placebo tablet matched to the moxifloxacin tablet ) on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 5 to 7 days.
Drug: Intranasal Esketamine
Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.
Drug: Intravenous Esketamine
Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.
Drug: Moxifloxacin
Participants will receive 400 mg Moxifloxacin orally.
Drug: Oral Placebo
Participants will receive matching placebo orally.
Drug: Intravenous Placebo
Participants will receive placebo 40 minutes, intravenous infusion.
Drug: Intranasal Placebo
Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).
Experimental: Sequence 2
Participants will receive Treatment A on Day 1 of period 1, Treatment C on Day 1 of period 2, Treatment B on Day 1 of period 3, Treatment D on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 5 to 7 days.
Drug: Intranasal Esketamine
Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.
Drug: Intravenous Esketamine
Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.
Drug: Moxifloxacin
Participants will receive 400 mg Moxifloxacin orally.
Drug: Oral Placebo
Participants will receive matching placebo orally.
Drug: Intravenous Placebo
Participants will receive placebo 40 minutes, intravenous infusion.
Drug: Intranasal Placebo
Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).
Experimental: Sequence 3
Participants will receive Treatment B on Day 1 of period 1, Treatment C on Day 1 of period 2, Treatment A on Day 1 of period 3, Treatment D on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 5 to 7 days.
Drug: Intranasal Esketamine
Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.
Drug: Intravenous Esketamine
Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.
Drug: Moxifloxacin
Participants will receive 400 mg Moxifloxacin orally.
Drug: Oral Placebo
Participants will receive matching placebo orally.
Drug: Intravenous Placebo
Participants will receive placebo 40 minutes, intravenous infusion.
Drug: Intranasal Placebo
Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).
Experimental: Sequence 4
Participants will receive Treatment B on Day 1 of period 1, Treatment A on Day 1 of period 2, Treatment C on Day 1 of period 3, Treatment D on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 5 to 7 days.
Drug: Intranasal Esketamine
Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.
Drug: Intravenous Esketamine
Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.
Drug: Moxifloxacin
Participants will receive 400 mg Moxifloxacin orally.
Drug: Oral Placebo
Participants will receive matching placebo orally.
Drug: Intravenous Placebo
Participants will receive placebo 40 minutes, intravenous infusion.
Drug: Intranasal Placebo
Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).
Experimental: Sequence 5
Participants will receive Treatment C on Day 1 of period 1, Treatment A on Day 1 of period 2, Treatment B on Day 1 of period 3, Treatment D on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 5 to 7 days.
Drug: Intranasal Esketamine
Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.
Drug: Intravenous Esketamine
Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.
Drug: Moxifloxacin
Participants will receive 400 mg Moxifloxacin orally.
Drug: Oral Placebo
Participants will receive matching placebo orally.
Drug: Intravenous Placebo
Participants will receive placebo 40 minutes, intravenous infusion.
Drug: Intranasal Placebo
Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).
Experimental: Sequence 6
Participants will receive Treatment C on Day 1 of period 1, Treatment B on Day 1 of period 2, Treatment A on Day 1 of period 3, Treatment D on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 5 to 7 days.
Drug: Intranasal Esketamine
Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.
Drug: Intravenous Esketamine
Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.
Drug: Moxifloxacin
Participants will receive 400 mg Moxifloxacin orally.
Drug: Oral Placebo
Participants will receive matching placebo orally.
Drug: Intravenous Placebo
Participants will receive placebo 40 minutes, intravenous infusion.
Drug: Intranasal Placebo
Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in QTc Interval
Time Frame: Up to Day 2
The QT interval corrected for heart rate (QTc interval) using Fridericia, Bazett and study-specific power correction methods, will be measured by electrocardiograms (ECG).
Up to Day 2
Percentage of Participants With Maximum Change From Baseline in Electrocardiogram (ECG) Morphology
Time Frame: Up to Day 2
Up to Day 2

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax)
Time Frame: Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Cmax is defined as maximum observed analyte concentration.
Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Area Under the Plasma Concentration Time Curve From Time Zero to 12 Hours (AUC [0-12])
Time Frame: Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
The AUC (0-12) is the area under the plasma concentration time curve from time 0 to 12 hours post-dose.
Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Area Under the Plasma Concentration Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUClast)
Time Frame: Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
The AUClast is area under the plasma concentration time curve from time zero to the last quantifiable concentration.
Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
Time Frame: Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
The AUC (0-infinity) is area under the plasma concentration time curve from time zero to infinite time, calculated as the sum of Area under Curve (AUC) last and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration.
Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Elimination Half-life Period (T1/2)
Time Frame: Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda[z]) of the semi logarithmic drug concentrationtime curve, and is calculated as 0.693/lambda(z).
Predose, 0.25, 0.33, 0.5, 0.67, 0.83, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 30 hours post-dose on Day 1
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Screening to follow-up visit (within 10 plus or minus 2 days after last dose administration)
Screening to follow-up visit (within 10 plus or minus 2 days after last dose administration)
Change From Baseline in Heart rate
Time Frame: Up to Day 2
Up to Day 2
Change From Baseline in QRS Interval
Time Frame: Up to Day 2
Up to Day 2
Change From Baseline in PR Interval
Time Frame: Up to Day 2
Up to Day 2
Change From Baseline in RR Interval
Time Frame: Up to Day 2
Up to Day 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 23, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 23, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 8, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 11, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR106218
  • 2014-004457-14 (EudraCT Number)
  • ESKETINTRD1013 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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