AzTrials
AzTrials

Drug AbusePhase 1NCT02682225

Crossover Study to Evaluate the Abuse Potential of Intranasal Esketamine Compared to Racemic Intravenous Ketamine in Nondependent, Recreational Drug Users

A Phase 1 study testing Intravenous racemic ketamine, Esketamine 112 mg and Esketamine 84 mg in people with Drug Abuse, run by Janssen Research & Development, LLC at 1 site in United States.

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 primary objective of this study is to evaluate the abuse potential of intranasal esketamine (112 milligram and 84 mg) compared to racemic intravenous ketamine (0.5 mg/kg) in nondependent, recreational polydrug users of perception-altering drugs. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Drug Abuse
What is being tested?
Intravenous racemic ketamine, Esketamine 112 mg and Esketamine 84 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
55 participants
Where
1 siteUnited States
Study dates
25 Mar 2016to 9 Jan 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

  • Participants with body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m^2) (inclusive), and body weight not less than 50 kg
  • 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, including the pharmacogenomic research component of the study
  • Be a current, recreational, nondependent, polydrug user defined as nonmedical use with at least 2 types of perception-altering drugs of abuse (example, lysergic acid diethylamide, cannabinoids, ketamine, ecstasy/3,4-methylenedioxy-methamphetamine, phencyclidine, psilocybin, and ring-substituted amphetamines with perception altering effects) and at least 10 total lifetime occasions of use with perception-altering drugs of abuse and who like their effects
  • Report having used ketamine at least once in a lifetime without moderate or severe adverse effects
  • Report having used a perception-altering drug (example, lysergic acid diethylamide, cannabinoids, ketamine, ecstasy/3,4-methylenedioxy-methamphetamine, phencyclidine, psilocybin, and ring substituted amphetamines with perception altering effects) at least once within 3 months prior to the screening phase without moderate or severe adverse effects

Who cannot join

  • Participant with a history of or current 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, hepatic or renal insufficiency, thyroid disease, neurologic disease, infection, hypertension or vascular disorder, kidney or urinary tract disturbances, 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
  • Participant has a current or prior diagnosis of psychotic or bipolar disorder
  • Participant with clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study center (Day -1 of the Qualification Session and each period of the Treatment Phase) as determined by the investigator
  • Participant with a history or presence of drug (excluding nicotine or caffeine) or alcohol dependence according to the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria
  • Participation in treatment for substance-related disorders within 3 years prior to Screening

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Study site

    Salt Lake City, Utah

Other trials in United States

About this study

Official title: A Single-Center, Single-Dose, Double-Blind, Double-Dummy, Placebo-Controlled, Randomized Crossover Study to Evaluate the Abuse Potential of Intranasal Esketamine Compared to Racemic Intravenous Ketamine in Nondependent, Recreational Users of Perception-Altering Drugs

The primary objective of this study is to evaluate the abuse potential of intranasal esketamine (112 milligram and 84 mg) compared to racemic intravenous ketamine (0.5 mg/kg) in nondependent, recreational polydrug users of perception-altering drugs.

Read the detailed description

This is a single-center, single-dose, double-blind, double-dummy, placebo-controlled (participants are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug), randomized (study medication assigned to participants by chance), crossover study in up to 120 men and women self-identifying as current, recreational, nondependent polydrug users. The study has a Screening Phase (consisting of a Screening Visit and a Qualification Session) and a Treatment Phase. In the Qualification Session participants will be randomized to receive Sequence 1: intravenous placebo and intranasal placebo concurrently (Treatment A) on Day 1 and an intravenous dose (0.5 mg/kg) of racemic ketamine and intranasal placebo concurrently (Treatment B) on Day 2, or the participants will receive Sequence 2: Treatment B on Day 1 and Treatment A on Day 2. In the Treatment Phase eligible participants will be administered 4 treatments: A, B, C (intravenous placebo and intranasal 84 mg esketamine as 3 devices, each with 28 mg esketamine followed by 1 device with placebo) and D (intravenous placebo and intranasal 112 mg of esketamine as 4 devices, each with 28 mg esketamine) in a cross-over manner (1 treatment per period) in Sequence 3, 4, 5, or 6. Periods 1, 2, 3, and 4 will be separated by 7 to 14 days. Primarily the drug abuse potential will be evaluated. Safety of the participants will be monitored throughout the study.

Conditions
Drug Abuse
Being tested
Intravenous placebo, Intranasal placebo, Intravenous racemic ketamine, Esketamine 112 mg, Esketamine 84 mg
Keywords
Esketamine, Placebo, Racemic ketamine, Pharmacokinetics
Medical subject headings
Substance-Related Disorders

What participants receive

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

  • Intravenous placeboDrug

    Participants will receive placebo, 40-minute, intravenous infusion on Day 1 of Sequence 1, on Day 2 of Sequence 2, on Day 1 of Period 1 in Sequence 3, 5 and 6, on Day 1 of Period 2 in Sequence 3, 4 and 6, on Day 1 of Period 3 in Sequence 4, 5 and 6, and on Day 1 of Period 4 in Sequence 3, 4 and 5.

  • Intranasal placeboDrug

    Participants will receive placebo, intranasally, on Day 1 or Day 2 in Sequence 1 and 2, on Day 1 of Period 1 in Sequence 3 and 4, on Day 1 of Period 2 in Sequence 4 and 5, on Day 1 of Period 3 in Sequence 3 and 6 and on Day 1 of Period 4 in Sequence 5 and 6.

  • Intravenous racemic ketamineDrug

    Participants will receive 0.5 mg/kg racemic ketamine, intranasally, on Day 2 in sequence 1, on Day 1 in sequence 2, on Day 1 of Period 1 in Sequence 4, on Day 1 of Period 2 in Sequence 5, on Day 1 of Period 3 in Sequence 3, and on Day 1 of Period 4 in Sequence 6.

  • Esketamine 112 mgDrug

    Participants will receive 112 mg of Esketamine, intranasally, on Day 1 of Period 1 in Sequence 6, on Day 1 of Period 2 in Sequence 3, on Day 1 of Period 3 in Sequence 5, and on Day 1 of Period 4 in Sequence 4.

  • Esketamine 84 mgDrug

    Participants will receive 84 mg of Esketamine, intranasally, on Day 1 of Period 1 in Sequence 5, on Day 1 of Period 2 in Sequence 6, on Day 1 of Period 3 in Sequence 4, and on Day 1 of Period 4 in Sequence 3.

Study groups in NCT02682225
Study groupRoleWhat they receive
Sequence 1: Qualification SessionExperimentalParticipants will receive Treatment A (intravenous placebo and intranasal placebo concurrently) on Day 1 and Treatment B (0.5 milligram per kilogram (mg/kg) of intravenous racemic ketamine and intranasal placebo concurrently) on Day 2.
Receives: Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine
Sequence 2: Qualification SessionExperimentalParticipants will receive Treatment B (0.5 mg/kg of intravenous racemic ketamine and intranasal placebo concurrently) on Day 1 and Treatment A (intravenous placebo and intranasal placebo concurrently) on Day 2.
Receives: Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine
Sequence 3: Treatment PhaseExperimentalParticipants in Sequence 3 will receive Treatment A (intravenous placebo and intranasal placebo) on Day 1 of period 1, Treatment D (intravenous placebo and intranasal 112 milligram (mg) of esketamine as 4 devices, each with 28 mg esketamine) on Day 1 of period 2, Treatment B (0.5 mg/kg of intravenous racemic ketamine and intranasal placebo) on Day 1 of period 3, Treatment C (intravenous placebo and intranasal 84 mg esketamine as 3 devices, each with 28 mg esketamine followed by 1 device with placebo) on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 7 to 14 days.
Receives: Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg
Sequence 4: Treatment PhaseExperimentalParticipants in Sequence 4 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 7 to 14 days.
Receives: Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg
Sequence 5: Treatment PhaseExperimentalParticipants in Sequence 5 will receive Treatment C on Day 1 of period 1, Treatment B on Day 1 of period 2, Treatment D on Day 1 of period 3, Treatment A on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 7 to 14 days.
Receives: Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg
Sequence 6: Treatment PhaseExperimentalParticipants in Sequence 6 will receive Treatment D on Day 1 of period 1, Treatment C on Day 1 of period 2, Treatment A on Day 1 of period 3, Treatment B on Day 1 of period 4. Periods 1, 2, 3 and 4 will be separated by 7 to 14 days.
Receives: Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg

What is being measured

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

  1. Change From Baseline in abuse potential based on Visual Analog Scale

    The abuse potential will be assessed based on visual analog scale (VAS). The VAS score will include for Balancing Measures, Positive and Negative effect at the moment, Perceptual / Dissociative Effects and others).

    Measured: up to Day 2 Period 4 in Treatment Phase

Secondary outcomes (16)

  1. Change From Baseline in Clinician-Administered Dissociative States Scale (CADSS) Score

    The CADSS is a clinician administered rating scale designed to measure dissociative symptoms. The CADSS comprises 23 subjective items, divided into 3 components: depersonalization, derealization and amnesia. Participant's responses are coded on a 5-point scale (0 = "Not at all" through to 4 = "Extremely). Higher scores indicate worsening

    Measured: up to Day 2 Period 4 in Treatment Phase

  2. Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score

    The C-SSRS is a clinical interview to assess severity and track suicidal events providing a summary of both suicidal ideation and behavior to identify the level and type of suicidality present.

    Measured: up to Day 2 Period 4 in Treatment Phase

  3. Percentage of Participants with Serious Adverse Events (SAEs) and Adverse Events (AEs)

    Measured: Screening to follow-up visit (11 to 13 days after last dose of study medication)

  4. Maximum Observed Plasma Concentration (Cmax)

    Cmax is defined as maximum observed analyte concentration.

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

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

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

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  6. 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, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  7. 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, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  8. 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, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  9. 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 concentration-time curve, and is calculated as 0.693/lambda(z).

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  10. First-order Rate Constant

    First-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  11. Total Body Clearance (CLT/F)

    Total body clearance will be calculated as dose/AUC(INF). AUC(INF) will be estimated as AUC(0-T) + Ct/λ z, where λ z is the terminal elimination rate constant and Ct is the last observable concentration

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  12. Volume of Distribution (Vd/F)

    The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  13. Cmax Metabolite to Parent Ratio (MPR Cmax)

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  14. AUC(last) Metabolite to Parent Ratio (MPR AUC[last])

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  15. AUC (infinity) Metabolite to Parent Ratio (MPR AUC [infinity])

    Measured: Predose, 0.17, 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours post-dose on Day 1

  16. Change from baseline in Nasal Tolerability Questionnaire

    Participants need to complete a nasal tolerability questionnaire from Screening to end of the study. The questionnaire will be containing different type symptoms with rating (None, mild, moderate and severe).

    Measured: up to Day 2 in Period 4 of Treatment Phase

Timeline

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

  1. First posted15 Feb 2016 (estimated)
  2. Study start25 Mar 2016
  3. Primary completion9 Jan 2017
  4. Study completion9 Jan 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
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02682225
Sponsor's protocol ID
CR108104
Other IDs
54135419TRD1015
Status last verified
Apr 2025
First submitted
10 Feb 2016
Last updated
27 Apr 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 Intravenous racemic ketamine, Esketamine 112 mg and Esketamine 84 mg in people with Drug Abuse, run by Janssen Research & Development, LLC at 1 site in United States.

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 27 Apr 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 United States. 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?

Change From Baseline in abuse potential based on Visual Analog Scale (time frame: up to Day 2 Period 4 in Treatment Phase). 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 NCT02682225, 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 27 Apr 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

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