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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
62
Participants will receive 84 mg intranasal esketamine as 3 devices, each with 28 mg esketamine.
Participants will receive 0.8 milligram per kilogram body weight esketamine, 40 minutes, intravenous infusion.
Participants will receive 400 mg Moxifloxacin orally.
Unnamed facility
Berlin, Germany
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).
Time frame: Up to Day 2
Percentage of Participants With Maximum Change From Baseline in Electrocardiogram (ECG) Morphology
Time frame: Up to Day 2
Maximum Observed Plasma Concentration (Cmax)
Cmax is defined as maximum observed analyte concentration.
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
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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
Area Under the Plasma Concentration Time Curve From Time Zero to 12 Hours (AUC [0-12])
The AUC (0-12) is the area under the plasma concentration time curve from time 0 to 12 hours post-dose.
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
Area Under the Plasma Concentration Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUClast)
The AUClast is area under the plasma concentration time curve from time zero to the last quantifiable concentration.
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
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Participants will receive matching placebo orally.
Participants will receive placebo 40 minutes, intravenous infusion.
Participants will receive intranasal placebo (1 spray in each nostril at 0, 5, and 10 minutes).
Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
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.
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
Elimination Half-life Period (T1/2)
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).
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
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