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

NCT02682225 | Completed Phase 1

• 2 other identifiers: CR10810454135419TRD1015
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Drug Abuse

Keywords

Esketamine; Placebo; Racemic ketamine; Pharmacokinetics

Outcome Measures

Primary Outcomes (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).

  up to Day 2 Period 4 in Treatment Phase

Secondary Outcomes (16)

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

  up to Day 2 Period 4 in Treatment Phase

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

  up to Day 2 Period 4 in Treatment Phase

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

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

• Maximum Observed Plasma Concentration (Cmax)

  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

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  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

Study Arms (6)

Sequence 1: Qualification Session

EXPERIMENTAL

Participants 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.

Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine

Sequence 2: Qualification Session

EXPERIMENTAL

Participants 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.

Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine

Sequence 3: Treatment Phase

EXPERIMENTAL

Participants 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.

Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg

Sequence 4: Treatment Phase

EXPERIMENTAL

Participants 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.

Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg

Sequence 5: Treatment Phase

EXPERIMENTAL

Participants 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.

Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg

Sequence 6: Treatment Phase

EXPERIMENTAL

Participants 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.

Drug: Intravenous placebo; Drug: Intranasal placebo; Drug: Intravenous racemic ketamine; Drug: Esketamine 112 mg; Drug: Esketamine 84 mg

Interventions

Intravenous placebo DRUG

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.

Sequence 1: Qualification Session; Sequence 2: Qualification Session; Sequence 3: Treatment Phase; Sequence 4: Treatment Phase; Sequence 5: Treatment Phase; Sequence 6: Treatment Phase

Intranasal placebo DRUG

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.

Sequence 1: Qualification Session; Sequence 2: Qualification Session; Sequence 3: Treatment Phase; Sequence 4: Treatment Phase; Sequence 5: Treatment Phase; Sequence 6: Treatment Phase

Intravenous racemic ketamine DRUG

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.

Sequence 1: Qualification Session; Sequence 2: Qualification Session; Sequence 3: Treatment Phase; Sequence 4: Treatment Phase; Sequence 5: Treatment Phase; Sequence 6: Treatment Phase

Esketamine 112 mg DRUG

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.

Sequence 3: Treatment Phase; Sequence 4: Treatment Phase; Sequence 5: Treatment Phase; Sequence 6: Treatment Phase

Esketamine 84 mg DRUG

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.

Sequence 3: Treatment Phase; Sequence 4: Treatment Phase; Sequence 5: Treatment Phase; Sequence 6: Treatment Phase

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Salt Lake City, Utah, United States

Location

Related Publications (1)

• 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.

  PMID: 33128208 DERIVED

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: February 15, 2016
• Study Start: March 25, 2016
• Primary Completion: January 9, 2017
• Study Completion: January 9, 2017
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

US (1)