The goal of this clinical trial is to determine the safety, tolerability and effects of Nezavist in healthy adults. The main questions it aims to answer are: * What is the safety and maximum tolerated dose (MTD) of orally administered Nezavist formulated as a spray dried dispersion (SDD) in healthy volunteers? * What are the pharmacokinetics (PK) of orally administered Nezavist SDD and its major metabolite (DCUKA) across a range of doses in healthy volunteers? Researchers will compare the active drug (Nezavist) and a placebo (an inactive substance that looks like the drug) to see if there is any differences between the two groups to make sure Nezavist is safe to use in future studies for reducing alcohol consumption by individuals that have alcohol use disorder (AUD).
Eligible participants will undergo intake procedures and baseline evaluations at the clinic the day before dosing. The next day, participants will be randomized to, and receive, either Nezavist SDD oral suspension or placebo vehicle (4 cohorts of escalating doses of Nezavist with 6 Nezavist subjects and 2 placebo subjects in each cohort). Participants will remain in the clinic for at least an additional 48-hours for safety assessments and blood collections to determine plasma levels of Nezavist, then will be discharged from the clinic and return for follow-up safety tests 72-hours later.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
29
Formulated as a spray dried dispersion (SDD) suspended in a flavored diluent.
Formulated in a diluent that matches the Nezavist SDD suspension in appearance.
The Altman Clinical and Translational Research Institute
La Jolla, California, United States
Safety, as measured by the severity, frequency, and relationship of adverse events (AEs) in participants
Safety is assessed by collecting AEs, including changes from baseline of vital signs, physical examinations, electrocardiograms, fecal occult blood tests, gastrointestinal symptoms and stool consistency, Profile of Moods State (POMS), and clinical laboratory tests (chemistry, hematology, coagulation tests, pregnancy tests, and urinalysis). AEs will be assessed daily after the start of dosing, with closer evaluations in the 12-hour period after the start of dosing
Time frame: Serious AEs from the time of informed consent (all other AEs from dosing) through to the follow up visit, up to 7 days, unless serious or if the study physician assesses them to be clinically significant
Maximum Tolerated Dose (MTD) of Nezavist in healthy volunteers
The MTD is considered the highest dose where no participants who receive active study drug met the study stopping criteria
Time frame: From dosing through to the follow up visit, up to 7 days
Pharmacokinetics AUC-t
Area under the plasma concentration-time curve from time 0 to the time (t) of last quantifiable concentration (Ct) calculated by the log-linear trapezoidal rule
Time frame: From predose through clinic release on Day 3
Pharmacokinetics AUC-infinity
Area under the plasma concentration-time curve from time 0 extrapolated to infinity. The terminal area from Ct to infinity is calculated by using the approximation as Ct/λz thus AUC∞ = AUCt + Ct/λz
Time frame: From predose through clinic release on Day 3
Pharmacokinetics Cmax
The maximum observed plasma concentration
Time frame: From predose through clinic release on Day 3
Pharmacokinetics tmax
The observed time to reach the maximum plasma concentration
Time frame: From predose through clinic release on Day 3
Pharmacokinetics λz
The terminal-phase exponential rate constant as calculated from the negative slope of the regression line for the terminal linear portion of the natural log (ln) transformed plasma concentration versus time curve
Time frame: From predose through clinic release on Day 3
Pharmacokinetics t1/2
The apparent terminal exponential half-life, calculated as ln(2)/λz
Time frame: From predose through clinic release on Day 3
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