The primary purpose of this study is to assess the effect of food on the rate and extent of absorption of a single dose of Zelquistinel 3 mg or 10 mg oral tablets tablets in healthy adult volunteers.
This is a randomized, open-label, single-dose, 2-cohort, 2-period crossover study to assess the effect of food on the pharmacokinetics, safety, and tolerability of zelquistinel tablet in healthy adult participants. Two dose levels, 3 and 10 mg, will each be evaluated for food effect, 1 dose level per cohort, with approximately 32 participants (16 per cohort). * Cohort 1: zelquistinel, 3 mg single oral tablet administered under fasted and fed conditions * Cohort 2: zelquistinel, 10 mg single oral tablet administered under fasted and fed conditions Study Design: This is a randomized, open-label, single-dose, 2-cohort, 2-period crossover study to assess the effect of food on the pharmacokinetics, safety, and tolerability of GATE-251 tablet in healthy adult participants. Two dose levels, 3 and 10 mg, will each be evaluated for food effect, 1 dose level per cohort, with approximately 32 participants (16 per cohort). * Cohort 1: zelquistinel, 3 mg single oral tablet administered under fasted and fed conditions * Cohort 2: zelquistinel, 10 mg single oral tablet administered under fasted and fed conditions After meeting eligibility requirements, participants will be admitted to the clinical research unit on Day -1. Participants within each cohort will be randomly assigned in a 1:1 ratio to a treatment sequence. Cohorts will be enrolled sequentially. Participants will only participate in 1 cohort. On Day 1 of each period, participants will receive one of the following treatments: * Treatment A (reference): zelquistinel, 3 mg tablet, fasted conditions * Treatment B (test): GATE-251, 3 mg tablet, fed conditions (high-fat, high-calorie meal) * Treatment C (reference): zelquistinel, 10 mg tablet, fasted conditions * Treatment D (test): zelquistinel, 10 mg tablet, fed conditions (high-fat, high-calorie meal) Fasted and fed conditions and test meal composition are defined by FDA guidance. For the fasted condition, zelquistinel will be administered after an overnight fast of at least 10 hours. For the fed condition, after an overnight fast of at least 10 hours, participants will start the test meal approximately 30 minutes before administration of zelquistinel. The test meal will be entirely consumed within 30 minutes. For both fasted and fed conditions, zelquistinel will be administered with approximately 240 mL of water. Up to 200 mL of additional water will be allowed in increments of 50 mL, as needed. No water will be allowed for at least 1 hour before or after zelquistinel administration, except for the water consumed during administration. No food will be allowed for at least 4 hours after zelquistinel administration. In addition, participants will be semi-recumbent during the test meal and for at least 4 hours after study drug administration, except for when procedures or adverse events require the supine position. The test meal will be a standard high-fat, high-calorie meal consisting of approximately 1000 calories with approximately 50% of the total calories from fat. There will be a 7-day washout interval between doses then participants will cross over to Period 2 and receive zelquistinel at the same dose as in Period 1 under the alternate fasted or fed condition. Participants will be confined to the clinical study unit from Study Day -1 through Study Day 10 and will return on approximately Study Day 15 (7±2 days from the last dose) for the Follow-Up Visit (end of study). Samples will be collected for pharmacokinetic analysis at the following timepoints for plasma, urine, and CSF. * Plasma: On Day 1 of each period, blood samples will be collected at: 0 (pre-dose) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours after dosing. * Urine: On Day 1 of each period, urine samples will be collected at: 0 (pre-dose) and 0-4-, 4-8-, 8-12-, and 12-24-hour intervals after dosing. * Cerebrospinal fluid (CSF) collection: On Day 1 of each period, CSF samples will be collected at: 0 (pre-dose) and 1, 2, 4, 8, 12, 16, and 24 hours after dosing. Safety assessments will include reporting of adverse events; clinical laboratory test results; vital sign measurements; electrocardiogram (ECG) results; and Columbia Suidical Severity Rating Scale (C-SSRS), Brief Psychiatric Rating Scale Positive Symptoms (BPRS+), and Clinician Administered Dissociative States Scale (CADSS) results. Adverse events, including serious adverse events (SAEs) and adverse events of special interest (AESIs), will be recorded from the time of informed consent until study completion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Subjects will receive Zelquistinel 3 mg in fed and fasted state (high fat meal).
Subjects will receive Zelquistinel 10 mg in fed and fasted state (high fat meal).
Dr. Vince Clinical Research
Overland Park, Kansas, United States
Pharmacokinetic parameter Maximum Concentration (Cmax) in plasma
Maximum concentration in plasma
Time frame: Hour zero to Hour 24
Pharmacokinetic parameter Area Under the Curve (AUC) for Concentration in plasma over time
Area under the curve from time 0 to hour 24
Time frame: Hour 0 to hour 24
Pharmacokinetic parameter Maximum Concentration (Cmax) in cerebrospinal fluid
Maximum concentration in cerebrospinal fluid in plasma
Time frame: Hour 0 to Hour 24
Pharmacokinetic parameter Area Under the Curve (AUC) for concentration in cerebrospinal fluid over time
Area under the curve from time 0 to hour 24 in cerebrospinal fluid
Time frame: Hour 0 to hour 24
Pharmacokinetic parameter Time of Maximum Concentration (Tmax) in plasma
Time of maximum concentration in plasma
Time frame: Hour 0 to hour 24
Pharmacokinetic parameter Elimination Half-Life (T1/2) in plasma
Elimination half life in plasma
Time frame: Hour 0 to hour 24
Pharmacokinetic parameter maximum concentration (Tmax) in cerebrospinal fluid
Time of maximum concentration in cerebrospinal fluid
Time frame: Hour 0 to hour 24
Pharmacokinetic parameter Elimination Half-Life (T1/2) in cerebrospinal fluid
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Ellimination half life in cerebrospinal fluid
Time frame: Hour 0 to hour 24
Safety - Pulse Rate
Evaluation of pulse rate
Time frame: Day -1 to Day 10
Safety - Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS assesses intensity of suicidal ideation with categories of increasing seriousness from Wish to be Dead (score 1), to Active Suicidal Ideation with Plan and Intent (score 5). The C-SSRS will be used to assess suicidal ideation and behaviors in participants who are able to complete the assessment.
Time frame: Day -1 to day 10
Safety - Brief Psychiatric Rating Scale, positive symptoms (BPRS+)
Evaluation of changes in psychotic ideation in the areas of conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content, each of which is scored from 1 (normal) to 4 (severe) with increasing intensity for a total score from 4 to 16.
Time frame: Day -1 to Day 10
Safety - Clinician-Administered Dissociative States Scale (CADSS)
Evaluation of changes in dissociative symptoms in 23 areas, each of which is scored from 0 - not present to 4 - severe, for a total score from 0 to 92.
Time frame: Day -1 to Day 10
Safety - Treatment Emergent Adverse Events (TEAE) reported by subjects after treatment has begun
Evaluation of side effects experienced by subjects after drug treatment has begun
Time frame: Day -1 to Day 10
Safety Systolic Blood Pressure
Change in systolic blood pressure
Time frame: Day -1 to Day 10
Safety Diastolic Blood Pressure
Change in diastolic blood pressure
Time frame: Day -1 to Day 10
Safety Body Temperature
Change in body temperature
Time frame: Day -1 to Day 10
Safety Electrocardiogram QT Interval
Change in electrocardiogram QT interval
Time frame: Day -1 to Day 10
Safety Electrocardiogram PR Interval
Change in electrocardiogram PR interval
Time frame: Day -1 to Day 10
Safety Electrocardiogram QRS Interval
Change in electrocardiogram QRS interval
Time frame: Day -1 to Day 10
Pharmacodynamics EEG alpha power
Change in EEG alpha power
Time frame: Day -1 to Day 10
Safety estimated Glomerular Filtration Rate (eGFR)
Change in estimated glomerular filtration rate
Time frame: Day -1 to Day 10