Safety, Tolerability, and Pharmacokinetics of EQU-001 in Healthy Volunteers

EQU-001 is a Phase 1 randomized, placebo-controlled, double-blind SAD/MAD study to evaluate safety, tolerability, PK, and high-fat food effects on EQU-001. Eight healthy adult participants will be enrolled in each of up to 5 cohorts in both the SAD and MAD portions of the study (10 mg, 20 mg, 40 mg, 80 mg, and 120 mg). The participants will be randomized 3:1, drug to placebo. The MAD dosing is for 14 days, to include a period of time where the study drug will be at steady-state. Eight participants from the SAD study (the 40 mg dose cohort or the MTD dose cohort, whichever dose is lower) will also complete a fed portion of the study.

This study of EQU-001 will provide baseline safety, tolerability, PK, and food effect data in healthy individuals and aims to identify drug-specific DLTs and an MTD. The PK component will characterize the PK of EQU-001 to inform dosing and may help to correlate exposures with any DLTs or other treatment-related AEs. The food effect component will characterize the effect of a high-fat meal on EQU-001 kinetics and exposure.

Inclusion criteria

• Age 18 to 65 years of age
• Weight 60 kg to 90 kg
• Willing and able to

• communicate in English or Spanish
• provide written informed consent to take part in the study
• be available for all visits and able and willing to comply with all study procedural requirements
• In general good health in the opinion of the investigator as defined by:

• The absence of clinically significant illness or surgery within 4 weeks of dosing. Participants vomiting within 24 hours before the first study drug administration will be carefully evaluated for upcoming illness/disease. Inclusion pre-dosing is at the discretion of the Investigator or designee.
• The absence of clinically significant neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease including uncontrolled diabetes.
• Agree not to participate in other concurrent interventional and/or drug trials
• Agree not to use nicotine containing products
• Agree not to eat grapefruit, drink grapefruit juice or take St. John's wort for 5 days prior to study drug dosing and throughout the study.
• If you or your heterosexual partner is pre-menopausal, you must agree to use an effective method of contraception and to continue use of an effective method for the duration of study participation and 2 weeks after. For this study, a clinical history of amenorrhea for ≥1 year without a separate identifiable cause and a medical history consistent with menopause meets criteria for post-menopausal. Acceptable methods are:

• condom use together with an additional barrier method plus spermicide, hormonal methods, or an IUD
• sterilization of participant or partner
• heterosexual abstinence

Exclusion criteria

• Pregnant or lactating
• History of hypersensitivity to the EQU-001 API
• History of EQU-001 API use within the previous 2 weeks
• History of ocular conditions that interfere with pupillometry including inability to focus on an object 3 meters in front of them, current eye disorder under the care of an ophthalmologist, or pupil not readily distinguishable from the iris
• History of excessive caffeine use (>8 cups of coffee or caffeine-containing energy drinks per day)
• History of smoking or vaping within the past 3 months
• History of substance abuse within 6 months (with the exception of medically indicated marijuana), including alcohol
• Use of concomitant prescription medications within 5 days of the study drug dose
• Use of an investigational drug or device or participation in an investigational study within 30 days prior to enrollment
• Donation of blood within the previous 4 weeks
• Has any of the following laboratory abnormalities at screening or baseline:

• Breathalyzer result ≥ 0.1
• Positive COVID test
• Positive urine drug screen
• Positive urine cotinine screen
• Total bilirubin or higher ≥ 1.5 x the site laboratory ULN
• ALT or ALT ≥ 2 x the site laboratory ULN
• HbA1c ≥ 6.5%
• Positive hCG (female pre-menopausal participants)
• Received a COVID-19 vaccine within 7 days of the baseline visit
• Any reason which, in the opinion of the PI, would prevent the subject from participating in the study