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

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ClinicalTrials.gov Identifier: NCT02737605
Recruitment Status : Completed
First Posted : April 14, 2016
Last Update Posted : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE April 8, 2016
First Posted Date  ICMJE April 14, 2016
Last Update Posted Date April 11, 2018
Actual Study Start Date  ICMJE July 1, 2016
Actual Primary Completion Date February 23, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2016)
  • 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).
  • Percentage of Participants With Maximum Change From Baseline in Electrocardiogram (ECG) Morphology [ Time Frame: Up to Day 2 ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2016)
  • 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).
  • Percentage of Participants with Maximim Change from Baseline in Electrocardiogram (ECG) Morphology [ Time Frame: Up to Day 2 ]
Change History Complete list of historical versions of study NCT02737605 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2016)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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) ]
  • Change From Baseline in Heart rate [ Time Frame: Up to Day 2 ]
  • Change From Baseline in QRS Interval [ Time Frame: Up to Day 2 ]
  • Change From Baseline in PR Interval [ Time Frame: Up to Day 2 ]
  • Change From Baseline in RR Interval [ Time Frame: Up to Day 2 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2016)
  • 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.
  • 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.
  • Area Under the Plasma ConcentrationTime 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 concentrationtime curve from time 0 to 12 hours postdose.
  • Area Under the Plasma ConcentrationTime 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 concentrationtime curve from time zero to the last quantifiable concentration.
  • Area Under the Plasma ConcentrationTime 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 concentrationtime 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.
  • Elimination HalfLife 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).
  • 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) ]
  • Change From Baseline in Heart rate [ Time Frame: Up to Day 2 ]
  • Change From Baseline in QRS Interval [ Time Frame: Up to Day 2 ]
  • Change From Baseline in PR Interval [ Time Frame: Up to Day 2 ]
  • Change From Baseline in RR Interval [ Time Frame: Up to Day 2 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Effects of Esketamine on Cardiac Repolarization in Healthy Participants
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • 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).
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Intranasal Esketamine
    • Drug: Intravenous Esketamine
    • Drug: Moxifloxacin
    • Drug: Oral Placebo
    • Drug: Intravenous Placebo
    • Drug: Intranasal Placebo
  • 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.
    Interventions:
    • Drug: Intranasal Esketamine
    • Drug: Intravenous Esketamine
    • Drug: Moxifloxacin
    • Drug: Oral Placebo
    • Drug: Intravenous Placebo
    • Drug: Intranasal Placebo
  • 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.
    Interventions:
    • Drug: Intranasal Esketamine
    • Drug: Intravenous Esketamine
    • Drug: Moxifloxacin
    • Drug: Oral Placebo
    • Drug: Intravenous Placebo
    • Drug: Intranasal Placebo
  • 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.
    Interventions:
    • Drug: Intranasal Esketamine
    • Drug: Intravenous Esketamine
    • Drug: Moxifloxacin
    • Drug: Oral Placebo
    • Drug: Intravenous Placebo
    • Drug: Intranasal Placebo
  • 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.
    Interventions:
    • Drug: Intranasal Esketamine
    • Drug: Intravenous Esketamine
    • Drug: Moxifloxacin
    • Drug: Oral Placebo
    • Drug: Intravenous Placebo
    • Drug: Intranasal Placebo
  • 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.
    Interventions:
    • Drug: Intranasal Esketamine
    • Drug: Intravenous Esketamine
    • Drug: Moxifloxacin
    • Drug: Oral Placebo
    • Drug: Intravenous Placebo
    • Drug: Intranasal Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 10, 2018)
62
Original Estimated Enrollment  ICMJE
 (submitted: April 8, 2016)
60
Actual Study Completion Date  ICMJE February 23, 2017
Actual Primary Completion Date February 23, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02737605
Other Study ID Numbers  ICMJE CR106218
2014-004457-14 ( EudraCT Number )
ESKETINTRD1013 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP