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HealthyPhase 1NCT02568176

Pharmacokinetic Study of Intranasal Esketamine and Its Effects on the Pharmacokinetics of Orally-Administered Midazolam and Bupropion in Healthy Participants

A Phase 1 study testing Midazolam, Esketamine and Bupropion in people with Healthy, run by Janssen Research & Development, LLC at 1 site in Belgium.

Completed

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

Official record
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Trial summary

The primary purpose of this study is to evaluate the induction potential of repeated administration of intranasal esketamine on cytochrome P450 (CYP) 3A4 and CYP2B6 activity in healthy participants using orally administered midazolam and bupropion as probes, respectively and to evaluate the pharmacokinetics of… 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?
Midazolam, Esketamine and Bupropion
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
1 siteBelgium
Study dates
Oct 2015to Feb 2016
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

  • Be a man or woman of non-Asian origin 18 to 55 years of age, inclusive
  • 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
  • A woman of child-bearing potential, must have a negative serum β-human chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine pregnancy test on Day -1 of the treatment period. Women using 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
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the investigator (eg, 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
  • Comfortable with self-administration of intranasal medication and able to follow instructions provided

Who cannot join

  • Clinically significant abnormal values for hematology, clinical chemistry (particularly potassium or magnesium levels below the normal laboratory range), or urinalysis at Screening or at admission to the study center (Day -1) as deemed appropriate by the investigator
  • Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or at admission to the study center (Day -1) as deemed appropriate by the investigator
  • Use of any prescription or non-prescription medication (including vitamins and herbal supplements), except for paracetamol, contraceptives, and hormonal replacement therapy, within 14 days before the first dose of the study drug is scheduled until completion of the study
  • Has used nasal tobacco powder ("snuff") regularly within the past year.
  • Has a nasal piercing

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • Study site

    Merksem

Other trials in Belgium

About this study

Official title: An Open-Label Study to Evaluate the Pharmacokinetics of Intranasal Esketamine and Its Effects on the Pharmacokinetics of Orally-Administered Midazolam and Bupropion in Healthy Subjects

The primary purpose of this study is to evaluate the induction potential of repeated administration of intranasal esketamine on cytochrome P450 (CYP) 3A4 and CYP2B6 activity in healthy participants using orally administered midazolam and bupropion as probes, respectively and to evaluate the pharmacokinetics of esketamine after a single dose and repeated administration.

Read the detailed description

This is a parallel group, single-center, repeat-dose, fixed-sequence, open-label (all people know the identity of the intervention), study. The effects of repeated administration of intranasal esketamine on the pharmacokinetics of midazolam and bupropion will be evaluated in Cohort 1 and Cohort 2, respectively. Participants in Cohort 1 will receive a single oral dose of midazolam in the morning of Day 1 and Day 17. Participants in Cohort 2 will receive a single oral dose of bupropion in the morning of Day 1 and Day 19. In Cohort 1 and 2 participants will self-administer 5 doses of intranasal esketamine over a 15-day period. The duration of study, from the Screening Phase through Follow-up, is up to 51 days and 54 days for Cohort 1 and Cohort 2, respectively. Blood samples for participants in Cohort 1 will be collected for up to 24 hours after dosing on Days 1 and 17 (midazolam) and for up to 24 hours on Days 2 and 16 (esketamine); For participants in Cohort 2, blood and urine samples for assessment of bupropion pharmacokinetics will be collected for up to 72 hours after dosing on Day 1 and Day 19. Participants' safety will be monitored throughout the study.

Conditions
Healthy
Being tested
Midazolam, Esketamine, Bupropion
Keywords
Healthy, Pharmacokinetics, Esketamine, JNJ-54135419, Midazolam, Bupropion

What participants receive

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

  • MidazolamDrug

    Single oral dose of midazolam 6 mg Day 1 and Day 17.

  • EsketamineDrug

    Also called JNJ-54135419

    Intranasal esketamine will be self-administered 5 times during 15 days.

  • BupropionDrug

    Single oral dose of bupropion 150 mg on Day 1 and 19.

Study groups in NCT02568176
Study groupRoleWhat they receive
Cohort 1ExperimentalParticipants will receive single oral dose of midazolam 6 milligram (mg) on Day 1 and 17. Participants will self-administer esketamine intranasally thrice per day on morning of Day 2, 5, 9, 12 and 16 (84 mg).
Receives: Drug: Midazolam; Drug: Esketamine
Cohort 2ExperimentalParticipants will receive single oral dose of bupropion 150 mg on Day 1 and 19. Participants will self-administer esketamine intranasally thrice per day on morning of Day 4, 7, 11, 14 and 18 (84 mg).
Receives: Drug: Esketamine; Drug: Bupropion

What is being measured

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

  1. Maximum Plasma Concentration (Cmax)

    The Cmax is the maximum plasma concentration.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  2. Time to reach maximum concentration (tmax)

    Time to reach the maximum observed plasma concentration.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  3. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])

    The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last])

    The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  5. Terminal Half-Life(t[1/2])

    Terminal half-life (t[(1/2]) is defined as 0.693/Lambda(z).

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  6. 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 zero to 12 hours, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  7. Cmax metabolite to parent ratio (MPR Cmax)

    Cmax metabolite to parent ratio, and corrected for molecular weight if necessary.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  8. AUC(last) metabolite to parent ratio (MPR AUC[last])

    AUC(last) metabolite to parent ratio, and corrected for molecular weight if necessary.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  9. AUC (infinity) metabolite to parent ratio (MPR AUC [infinity])

    AUC (infinity) metabolite to parent ratio, and corrected for molecular weight if necessary.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  10. Amount of Drug excreted in Urine (Ae)

    Total amount excreted into the urine, calculated as the sum of all Ae(t1-t2) intervals.

    Measured: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2

  11. Percentage of Drug dose excreted into urine

    Total amount excreted into the urine, expressed as a percentage of the administered dose, calculated as (Ae/dose)*100, and corrected for molecular weight if necessary.

    Measured: up to Day 19 for Cohort 2

  12. Renal clearance

    Renal clearance calculated as Ae/AUC (infinity).

    Measured: up to Day 19 for Cohort 2

  13. Formation Clearance

    Formation clearance of drug, calculated as Ae of hydroxybupropion/AUC(infinity) of bupropion, and corrected for molecular weight if necessary.

    Measured: up to Day 19 for Cohort 2

  14. Ae metabolite to parent ratio (MPR Ae)

    Ae metabolite to parent ratio, and corrected for molecular weight if necessary.

    Measured: up to Day 19 for Cohort 2

Secondary outcomes (1)
  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

    Measured: Baseline up to Day 51 for Cohort 1; Baseline up to Day 54 Cohort 2

Timeline

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

  1. First posted5 Oct 2015 (estimated)
  2. Study startOct 2015
  3. Primary completionFeb 2016
  4. Study completionFeb 2016

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02568176
Sponsor's protocol ID
CR108043
Other IDs
ESKETINTRD1010, 2015-002654-13, 2015
Status last verified
Jan 2025
First submitted
2 Oct 2015
Last updated
3 Feb 2025
Results posted
No
Data monitoring committee
No

Publications

  • Perez-Ruixo C, Rossenu S, Zannikos P, Nandy P, Singh J, Drevets WC, Perez-Ruixo JJ. Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. Clin Pharmacokinet. 2021 Apr;60(4):501-516. doi: 10.1007/s40262-020-00953-4. Epub 2020 Oct 31.

    PubMed 33128208

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Midazolam, Esketamine and Bupropion in people with Healthy, run by Janssen Research & Development, LLC at 1 site in Belgium.

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 3 Feb 2025. 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 Belgium. 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?

Maximum Plasma Concentration (Cmax) (time frame: up to Day 17 for Cohort 1; up to Day 19 for Cohort 2). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02568176, which also lists 1 linked publication.

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 3 Feb 2025.

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