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

Healthy Clinical Trial

Official title:

A Randomized, Participant- and Investigator Blind, Double Dummy, Placebo- and Comparator-controlled, Single Ascending Dose and Parallel-group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Different Modes of (S) Ketamine Administration in Healthy Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03808259
• Other study ID #: CR108553
• Secondary ID: 2018-003435-3054
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2018
• Est. completion date: September 4, 2019

Study information

• Verified date: September 2019
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: September 4, 2019
• Est. primary completion date: September 4, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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)

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• (S)-ketamine Oral Thin Film
(S)-ketamine OTF sublingual formulation at a dose of 7 mg, 14 mg, and 28 mg will be administered in sequential cohorts.
• (S)-ketamine IV Infusion
(S)-ketamine IV solution will be infused at a dose of less than or equal to 14mg.
• Placebo
Participants will receive matching placebo.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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

External Links

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