A Study to Investigate the Different Modes of (S) Ketamine Administration in Healthy Participants

NCT03808259 | Completed Phase 1

• 3 other identifiers: CR1085532018-003435-3054135419EDI1001
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of different modes of (S) ketamine administration in healthy participants.

Conditions

Healthy

Outcome Measures

Primary Outcomes (10)

• Part 1: Change from Baseline in Clinician-Administered Dissociative States Scale (CADSS) Total Score

  CADSS is an instrument for the measurement of present-state dissociative symptoms and will be administered to assess treatment-emergent dissociative symptoms. CADSS consists of 23 subjective items, divided into 3 components: depersonalization (items 3 to 7, 20, and 23), derealization (items 1, 2, 8 to 13, 16 to 19, and 21) and amnesia (items 14, 15, and 22). The participants responses are coded on a 5-point scale (from 0=not at all to 4=extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.

  Baseline up to Day 1

• Part 2: Change from Baseline in CADSS Total Score

  CADSS is an instrument for the measurement of present-state dissociative symptoms and will be administered to assess treatment-emergent dissociative symptoms. CADSS consists of 23 subjective items, divided into 3 components: depersonalization (items 3 to 7, 20, and 23), derealization (items 1, 2, 8 to 13, 16 to 19, and 21) and amnesia (items 14, 15, and 22). The participants responses are coded on a 5-point scale (from 0=not at all to 4=extremely). The total score is sum of the 23 items and range from 0 to 92 - best is 0 and worst is 92.

  Baseline up to Day 1

• Part 1: Number of Participants with Vital Sign Abnormalities

  Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.

  Up to Day 2

• Part 2: Number of Participants with Vital Sign Abnormalities

  Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.

  Up to Day 2

• Plasma Concentrations of (S)-ketamine

  Observed plasma concentrations of (S)-ketamine will be reported.

  Part 1: Predose, 1, 3, 5, 10, 15, 30, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hour postdose; Part 2: predose, 15, 30 min, 1, 1.6, 2, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours postdose

• Plasma Concentrations of Nor(S)-ketamine

  Observed plasma concentrations of Nor(S)-ketamine will be reported.

  Part 1: Predose, 1, 3, 5, 10, 15, 30, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hour postdose; Part 2: predose, 15, 30 min, 1, 1.6, 2, 3, 3.5, 4, 6, 8, 10, 12 and 24 hours postdose

• Part 1: Change from Baseline in Electroencephalogram (EEG) Power

  EEG power spectral activity in the alpha 1, alpha 2, beta 1, beta 2, delta, theta and gamma frequency bands will be estimated for the baseline EEG recording and will be compared to the EEG power spectral activity in the same frequency bands.

  Predose (Baseline) and 2.25 hours postdose

• Part 2: Change from Baseline in EEG Power

  EEG power spectral activity in the alpha 1, alpha 2, beta 1, beta 2, delta, theta and gamma frequency bands will be estimated for the baseline EEG recording and will be compared to the EEG power spectral activity in the same frequency bands.

  Predose (Baseline) and 3.25 hours postdose

• Part 1: Change from Baseline in Continuous Paired Associate Learning Test (cPALT) Score

  The cPALT will be used to assess whether drug will improve performance of complex cognitive tasks. CPAL assesses Visual episodic memory (associate learning) cognitive domain. In this task, participants must learn a series of associations between a set of difficult to verbalize patterns (amoeba) and locations. In participants, 14 pattern/location associations must be learned. In the presentation phase of the task the pattern appears at the location and the participant is required to acknowledge that they have seen the pattern by touching the location at which it appears. Patterns are presented in random order. In the learning phase of the task, participants must place each of the 14 patterns in their correct locations. They must do this in 10 rounds. The outcome is number of errors made in correctly placing each of the four patterns in their location four times (Lower score = better performance).

  Baseline up to Day 1

• Part 2: Change from Baseline in cPALT Score

  The cPALT will be used to assess whether drug will improve performance of complex cognitive tasks. CPAL assesses Visual episodic memory (associate learning) cognitive domain. In this task, participants must learn a series of associations between a set of difficult to verbalize patterns (amoeba) and locations. In participants, 14 pattern/location associations must be learned. In the presentation phase of the task the pattern appears at the location and the participant is required to acknowledge that they have seen the pattern by touching the location at which it appears. Patterns are presented in random order. In the learning phase of the task, participants must place each of the 14 patterns in their correct locations. They must do this in 10 rounds. The outcome is number of errors made in correctly placing each of the four patterns in their location four times (Lower score = better performance).

  Baseline up to Day 1

Study Arms (2)

Part 1: OTF Sublingual and IV

EXPERIMENTAL

Participants will receive (S)-ketamine oral thin film (OTF) at a dose of 7 milligram (mg) \[cohort 1\], 14 mg \[cohort 2\], and 28 mg \[cohort 3\] via sublingual route or 14 mg (S)-ketamine intravenous (IV) infusion for 40 minutes or matching placebo in 1 of 3 serial cohorts. Dose escalation decisions to further cohorts of Part 1 will be made based on safety and tolerability profile of the preceding lower dose level.

Drug: (S)-ketamine Oral Thin Film; Drug: (S)-ketamine IV Infusion; Drug: Placebo

Part 2: IV Different Infusion Duration

EXPERIMENTAL

Participants will receive single dose (S)-ketamine less than or equal to (\<=)14 mg IV at a different infusion duration or matching placebo at a different infusion duration. The infusion duration and dose will be chosen after completion of Part 1.

Drug: (S)-ketamine IV Infusion; Drug: Placebo

Interventions

(S)-ketamine Oral Thin Film DRUG

(S)-ketamine OTF sublingual formulation at a dose of 7 mg, 14 mg, and 28 mg will be administered in sequential cohorts.

Also known as: JNJ-54135419

Part 1: OTF Sublingual and IV

(S)-ketamine IV Infusion DRUG

(S)-ketamine IV solution will be infused at a dose of less than or equal to 14mg.

Also known as: Ketanest

Part 1: OTF Sublingual and IV; Part 2: IV Different Infusion Duration

Placebo DRUG

Participants will receive matching placebo.

Part 1: OTF Sublingual and IV; Part 2: IV Different Infusion Duration

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body Mass Index (BMI) between 20 and 28 kilogram per meter square (kg/m\^2), inclusive (BMI=weight/height\^2) with a minimum weight of 60 kilogram (kg) and a maximum of 100 kg
• Participant must have systolic blood pressure (SBP) and heart rate (HR) within normal limits at screening and at Day -1: supine SBP of at least 90 millimeters of mercury (mmHg) and maximum 150mmHg, supine diastolic blood pressure (DBP) should be above 50mmHg and below 90mmHg and the HR must be between 45 beats per minute (BPM) and 100 BPM. If the results are outside the normal reference ranges above, retesting will be allowed once during the screening phase
• Non-smoker (not smoked for 3 months prior to screening)

You may not qualify if:

• Cardiac arrhythmias or other cardiac disease, hematological disease, hypertension, lipid abnormalities, respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, Parkinson's disease, infection, or any other illness that the Investigator considers should exclude the participant
• Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies at screening visit
• Participant has a history of drug or alcohol use disorder or psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 6 months before screening (for example psychotic, bipolar, major depressive, or anxiety disorder) or positive test result(s) for alcohol and/or drugs of abuse (opiates (including methadone), cocaine, amphetamines, methamphetamines, cannabinoids, barbiturates, ecstasy and benzodiazepines) at screening or admission
• Drinks, on average, more than 8 cups of tea/coffee/cocoa/cola per day
• Clinically significant acute illness within 7 days prior to study drug administration

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

Ketamine

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

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: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 17, 2019
• Study Start: December 20, 2018
• Primary Completion: September 4, 2019
• Study Completion: September 4, 2019
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)