Clinical trial NCT03808259: A Study to Investigate the Different Modes of (S) Ketamine Administration in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-01-17
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Change from Baseline in Clinician-Administered Dissociative States Scale (CADSS) Total Score
timeFrame: Baseline up to Day 1
measure: Part 2: Change from Baseline in CADSS Total Score
timeFrame: Baseline up to Day 1
measure: Part 1: Number of Participants with Vital Sign Abnormalities
timeFrame: Up to Day 2
measure: Part 2: Number of Participants with Vital Sign Abnormalities
timeFrame: Up to Day 2
measure: Plasma Concentrations of (S)-ketamine
timeFrame: 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
measure: Plasma Concentrations of Nor(S)-ketamine
timeFrame: 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
measure: Part 1: Change from Baseline in Electroencephalogram (EEG) Power
timeFrame: Predose (Baseline) and 2.25 hours postdose
measure: Part 2: Change from Baseline in EEG Power
timeFrame: Predose (Baseline) and 3.25 hours postdose
measure: Part 1: Change from Baseline in Continuous Paired Associate Learning Test (cPALT) Score
timeFrame: Baseline up to Day 1
measure: Part 2: Change from Baseline in cPALT Score
timeFrame: Baseline up to Day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: