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

NCT02737605 | Completed Phase 1

• 3 other identifiers: CR1062182014-004457-14ESKETINTRD1013
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Esketamine; Healthy; Pharmacokinetics; Electrocardiogram; Repolarization

Outcome Measures

Primary Outcomes (2)

• Mean Change From Baseline in QTc Interval

  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

  Up to Day 2

Secondary Outcomes (11)

• Maximum Observed Plasma Concentration (Cmax)

  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)

  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])

  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)

  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])

  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

Study Arms (6)

Sequence 1

EXPERIMENTAL

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; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo

Sequence 2

EXPERIMENTAL

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; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo

Sequence 3

EXPERIMENTAL

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; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo

Sequence 4

EXPERIMENTAL

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; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo

Sequence 5

EXPERIMENTAL

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; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo

Sequence 6

EXPERIMENTAL

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; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo

Interventions

Intranasal Esketamine DRUG

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

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Intravenous Esketamine DRUG

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

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Moxifloxacin DRUG

Participants will receive 400 mg Moxifloxacin orally.

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Oral Placebo DRUG

Participants will receive matching placebo orally.

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Intravenous Placebo DRUG

Participants will receive placebo 40 minutes, intravenous infusion.

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Intranasal Placebo DRUG

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

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Berlin, Germany

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2016
• First Posted: April 14, 2016
• Study Start: July 1, 2016
• Primary Completion: February 23, 2017
• Study Completion: February 23, 2017
• Last Updated: April 11, 2018

Record last verified: 2018-04

Locations

DE (1)