AzTrials
AzTrials

HealthyPhase 1NCT02737605

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

A Phase 1 study testing Intranasal Esketamine, Intravenous Esketamine and Moxifloxacin in people with Healthy, run by Janssen Research & Development, LLC at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Intranasal Esketamine, Intravenous Esketamine and Moxifloxacin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
62 participants
Where
1 siteGermany
Study dates
1 Jul 2016to 23 Feb 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Study site

    Berlin

Other trials in Germany

About this study

Official title: 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.

Read the 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.

Conditions
Healthy
Being tested
Intranasal Esketamine, Intravenous Esketamine, Moxifloxacin, Oral Placebo, Intravenous Placebo
Keywords
Esketamine, Healthy, Pharmacokinetics, Electrocardiogram, Repolarization

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intranasal EsketamineDrug

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

  • Intravenous EsketamineDrug

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

  • MoxifloxacinDrug

    Participants will receive 400 mg Moxifloxacin orally.

  • Oral PlaceboDrug

    Participants will receive matching placebo orally.

  • Intravenous PlaceboDrug

    Participants will receive placebo 40 minutes, intravenous infusion.

  • Intranasal PlaceboDrug

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

Study groups in NCT02737605
Study groupRoleWhat they receive
Sequence 1ExperimentalParticipants 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.
Receives: Drug: Intranasal Esketamine; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo
Sequence 2ExperimentalParticipants 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.
Receives: Drug: Intranasal Esketamine; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo
Sequence 3ExperimentalParticipants 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.
Receives: Drug: Intranasal Esketamine; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo
Sequence 4ExperimentalParticipants 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.
Receives: Drug: Intranasal Esketamine; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo
Sequence 5ExperimentalParticipants 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.
Receives: Drug: Intranasal Esketamine; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo
Sequence 6ExperimentalParticipants 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.
Receives: Drug: Intranasal Esketamine; Drug: Intravenous Esketamine; Drug: Moxifloxacin; Drug: Oral Placebo; Drug: Intravenous Placebo; Drug: Intranasal Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Up to Day 2

  2. Percentage of Participants With Maximum Change From Baseline in Electrocardiogram (ECG) Morphology

    Measured: Up to Day 2

Secondary outcomes (11)
  1. Maximum Observed Plasma Concentration (Cmax)

    Cmax is defined as maximum observed analyte concentration.

    Measured: 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

  2. Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

    Measured: 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

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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).

    Measured: 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

  7. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: Screening to follow-up visit (within 10 plus or minus 2 days after last dose administration)

  8. Change From Baseline in Heart rate

    Measured: Up to Day 2

  9. Change From Baseline in QRS Interval

    Measured: Up to Day 2

  10. Change From Baseline in PR Interval

    Measured: Up to Day 2

  11. Change From Baseline in RR Interval

    Measured: Up to Day 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2016 (estimated)
  2. Study start1 Jul 2016
  3. Primary completion23 Feb 2017
  4. Study completion23 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02737605
Sponsor's protocol ID
CR106218
Other IDs
2014-004457-14, ESKETINTRD1013, 2014
Status last verified
Apr 2018
First submitted
8 Apr 2016
Last updated
11 Apr 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Intranasal Esketamine, Intravenous Esketamine and Moxifloxacin in people with Healthy, run by Janssen Research & Development, LLC at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in QTc Interval (time frame: Up to Day 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2018.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in