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

NCT ID: NCT02737605

Last Updated: 2018-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-01

Study Completion Date

2017-02-23

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Intranasal Esketamine

Intervention Type DRUG

Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.

Intravenous Esketamine

Intervention Type DRUG

Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.

Moxifloxacin

Intervention Type DRUG

Participants will receive 400 mg Moxifloxacin orally.

Oral Placebo

Intervention Type DRUG

Participants will receive matching placebo orally.

Intravenous Placebo

Intervention Type DRUG

Participants will receive placebo 40 minutes, intravenous infusion.

Intranasal Placebo

Intervention Type DRUG

Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

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.

Group Type EXPERIMENTAL

Intranasal Esketamine

Intervention Type DRUG

Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.

Intravenous Esketamine

Intervention Type DRUG

Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.

Moxifloxacin

Intervention Type DRUG

Participants will receive 400 mg Moxifloxacin orally.

Oral Placebo

Intervention Type DRUG

Participants will receive matching placebo orally.

Intravenous Placebo

Intervention Type DRUG

Participants will receive placebo 40 minutes, intravenous infusion.

Intranasal Placebo

Intervention Type DRUG

Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

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.

Group Type EXPERIMENTAL

Intranasal Esketamine

Intervention Type DRUG

Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.

Intravenous Esketamine

Intervention Type DRUG

Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.

Moxifloxacin

Intervention Type DRUG

Participants will receive 400 mg Moxifloxacin orally.

Oral Placebo

Intervention Type DRUG

Participants will receive matching placebo orally.

Intravenous Placebo

Intervention Type DRUG

Participants will receive placebo 40 minutes, intravenous infusion.

Intranasal Placebo

Intervention Type DRUG

Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

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.

Group Type EXPERIMENTAL

Intranasal Esketamine

Intervention Type DRUG

Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.

Intravenous Esketamine

Intervention Type DRUG

Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.

Moxifloxacin

Intervention Type DRUG

Participants will receive 400 mg Moxifloxacin orally.

Oral Placebo

Intervention Type DRUG

Participants will receive matching placebo orally.

Intravenous Placebo

Intervention Type DRUG

Participants will receive placebo 40 minutes, intravenous infusion.

Intranasal Placebo

Intervention Type DRUG

Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

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.

Group Type EXPERIMENTAL

Intranasal Esketamine

Intervention Type DRUG

Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.

Intravenous Esketamine

Intervention Type DRUG

Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.

Moxifloxacin

Intervention Type DRUG

Participants will receive 400 mg Moxifloxacin orally.

Oral Placebo

Intervention Type DRUG

Participants will receive matching placebo orally.

Intravenous Placebo

Intervention Type DRUG

Participants will receive placebo 40 minutes, intravenous infusion.

Intranasal Placebo

Intervention Type DRUG

Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

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.

Group Type EXPERIMENTAL

Intranasal Esketamine

Intervention Type DRUG

Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.

Intravenous Esketamine

Intervention Type DRUG

Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.

Moxifloxacin

Intervention Type DRUG

Participants will receive 400 mg Moxifloxacin orally.

Oral Placebo

Intervention Type DRUG

Participants will receive matching placebo orally.

Intravenous Placebo

Intervention Type DRUG

Participants will receive placebo 40 minutes, intravenous infusion.

Intranasal Placebo

Intervention Type DRUG

Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

Interventions

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Intranasal Esketamine

Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.

Intervention Type DRUG

Intravenous Esketamine

Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.

Intervention Type DRUG

Moxifloxacin

Participants will receive 400 mg Moxifloxacin orally.

Intervention Type DRUG

Oral Placebo

Participants will receive matching placebo orally.

Intervention Type DRUG

Intravenous Placebo

Participants will receive placebo 40 minutes, intravenous infusion.

Intervention Type DRUG

Intranasal Placebo

Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Berlin, , Germany

Site Status

Countries

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Germany

Other Identifiers

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2014-004457-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ESKETINTRD1013

Identifier Type: OTHER

Identifier Source: secondary_id

CR106218

Identifier Type: -

Identifier Source: org_study_id

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