central nervous system disorders
Conditions
Interventions
Three study drugs or placebo 
will be administered to the subjects. 
S-ketamine 
0.475 mg/kg for 75 min + 0.275 mg/kg for 75 min IV, modafinil 200 mg PO, and lorazepam 2 mg PO 
will be prepared with matching placebo formulations, including capsules and a NaCl 0.9% solution. For modafinil, two 100 mg tablets will be encapsulated for blinding, resulting in two administered cap
For lorazepam, two 1 mg tablets will be encapsulated for blinding, resulting in two administered capsules for the total dose of 2 mg. 
Administration will occur in a double-dummy fashion, thus, subjects will each time receive four capsules PO and one IV administration. IV S-ketamine or placebo will be administered for 150 minutes at
Matching placebo will consist of a saline solution or encapsulated placebo capsule. S-ketamine dosing will be individually prepared based on the subject weight at screening. 
Prior to each dosing the subject will be weighed again. If the change in weight is 15% or more relative to the weight at screening, the dose must be adjusted to the new weight.
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Healthy female or male participants, 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical, surgical and psychiatric history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis. - Body mass index (BMI) between 18 and 32 kg/m^2, inclusive, with a minimum weight of 50 kg. - A self-reported normal or corrected vision.- Use of any form of birth control is required for heterosexual subjects of childbearing potential who are sexually active during the study, either used by the subject or their sexual partner. - Female subjects of childbearing potential are required to have a negative urine ß-hCG test at screening and pre-dose. - Participants are willing to give a written informed consent (ICF) in Dutch and adhere to the lifestyle restrictions.
Exclusion criteria
Exclusion criteria: - Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). - Clinically significant abnormalities on ECG, as judged by the investigator, including evidence of atrial fibrillation, cardiac arrythmia, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker. - Untreated hypertension defined as SBP greater than 140 mmHg or DBP greater than 90 mmHg at screening. The measurement may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. - Clinically significant respiratory insufficiency, problems with free airway (as sleep apnea) or muscle conditions limiting breathing (such as myasthenia gravis). - (History of) increased intracranial pressure.- History of active malignancy within the last 5 years before screening, with the exception of localized or in situ carcinoma (e.g., skin basal or squamous cell carcinoma). - Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. - Current diagnosis, personal history or family history of a clinically significant psychiatric disorder, including substance use disorder or suicidality, at screening. - A self-reported history of symptoms indicative of any clinically significant disorder including neurological, cognitive or psychiatric diseases at screening. - History of abuse of alcohol or current use of more than 21 units alcohol per week. Consumption of alcoholic beverages within 24 hours prior to screening or pre-dose. Positive alcohol breath test at screening or pre-dose. - History of abuse of addictive substances or current abuse, regular user of sedatives, hypnotics, tranquilizers, or any other addictive agent; and/or recreational use of ketamine on 2 or more occasions within 12 months of screening.- Consumption of illegal drugs within 7 days (within 6 weeks for cannabis or THC) before screening or pre-dose. Positive urine test for drugs of abuse (e.g barbiturates, phencyclidine, cocaine, opiates or amphetamines) at screening or pre-dose.- Use of any medication (prescription including psychoactive compounds, or over-the-counter [OTC]), vitamin, mineral, herbal, and dietary supplements within 14 days, or less than 5 half-lives (whichever is longer), of study drug administration.- Smoking more than 5 cigarettes per day within 3 months prior to screening or inability to refrain from using nicotine products from 24 hours pre-dose until discharge from the clinic. - Performing strenuous physical exercise within 48 hours prior to each admission to the clinical research unit.- Excessive caffeine consumption, defined as >800 mg per day from 7 days prior to the first dose of the study drug until 24 hours prior to dosing and during wash-out periods in between occasions, in addition to any caffeine consumption from 24 hours prior to the start of dosing until discharge from the study unit. Caffeine quantities defined as: one cup of coffee contains 100 mg of caffeine; one cup of tea, or one glass of cola, or potion of chocolate (dark:100 g, milk 200 g) contains approximately 40 mg of caffeine; one bottle of Red Bull contains approximately 80 mg of caffeine.- Confirmed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoints:Saccadic eye movement (NeuroKit and NeuroCart)Smooth pursuit eye movement (NeuroKit and NeuroCart)Adaptive tracking (NeuroKit and NeuroCart)Body swayN-Back (NeuroKit and NeuroCart)Finger Tapping (NeuroKit and NeuroCart)VAS Bowdle (NeuroKit and NeuroCart)VAS B&L (NeuroKit and NeuroCart)The 90% confidence interval of the ratio of effect sizes of NeuroKit and NeuroCart, of each PD endpoint per treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints:Lorazepam, modafinil and S-ketamine concentration in plasmaPlasma PK endpointsProportion of fully executed VR measurements in %CADSS questionnaire | — |
Countries
Netherlands
Contacts
Public ContactG.E. Jacobs
Centre for Human Drug Research
Outcome results
None listed