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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: (S)-ketamine IV Infusion; Drug: (S)-ketamine Oral Thin Film; Drug: Placebo

• Registration Number: NCT03808259
• Lead Sponsor: Janssen Research & Development, LLC

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-12-20
• Study First Submitted: 2019-01-04
• Study First Submitted QC: 2019-01-16
• Study First Posted: 2019-01-17
• Status Verified: 2019-09
• Primary Completion: 2019-09-04
• Study Completion: 2019-09-04
• Last Update Submitted: 2019-09-10
• Last Update Posted: 2019-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

• 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 be healthy based on clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology or urinalysis are outside the normal reference ranges, retesting of an abnormal lab value(s) that may lead to exclusion will be allowed once during the screening phase
• Participant must be healthy based on physical and neurological examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) (including QT corrected according to Fridericia's formula [QTcF] less than or equal to [<=] 450 milliseconds [msec] for males and <= 470 msec for females) performed at screening. Abnormalities, which are not considered to be of clinical significance by the Investigator, are acceptable. The presence of left bundle branch block (LBBB), atrioventricular (AV) Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator (ICD) will lead to exclusion
• 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)

Read More

Exclusion Criteria

• 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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2: IV Different Infusion Duration	(S)-ketamine IV Infusion	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.
Part 1: OTF Sublingual and IV	(S)-ketamine IV Infusion	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.
Part 1: OTF Sublingual and IV	(S)-ketamine Oral Thin Film	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.
Part 1: OTF Sublingual and IV	Placebo	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.
Part 2: IV Different Infusion Duration	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Part 1: Change from Baseline in Clinician-Administered Dissociative States Scale (CADSS) Total Score	Baseline up to Day 1	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.
Part 2: Change from Baseline in CADSS Total Score	Baseline up to Day 1	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.
Part 1: Number of Participants with Vital Sign Abnormalities	Up to Day 2	Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.
Part 2: Number of Participants with Vital Sign Abnormalities	Up to Day 2	Number of participants with vital signs (Heart Rate and Blood Pressure) abnormalities will be reported.
Plasma Concentrations of (S)-ketamine	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	Observed plasma concentrations of (S)-ketamine will be reported.
Plasma Concentrations of Nor(S)-ketamine	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	Observed plasma concentrations of Nor(S)-ketamine will be reported.
Part 1: Change from Baseline in Electroencephalogram (EEG) Power	Predose (Baseline) and 2.25 hours postdose	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.
Part 2: Change from Baseline in EEG Power	Predose (Baseline) and 3.25 hours postdose	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.
Part 1: Change from Baseline in Continuous Paired Associate Learning Test (cPALT) Score	Baseline up to Day 1	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).
Part 2: Change from Baseline in cPALT Score	Baseline up to Day 1	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).

Trial Locations

Locations (1)

Clinical Pharmacology Unit; 🇧🇪 Merksem, Belgium