The Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers

-INCLUSION CRITERIA:

• Must have the ability to understand and must personally sign a written informed consent form, which must be obtained prior to initiation of study procedures.
• Must be between 18 and 65 years of age, inclusive.
• Must have discontinued use of nicotine and nicotine containing products including vaping or juuling from 90 days prior to study drug dosing and throughout the study duration.
• Must be willing to abstain from any food or beverages containing alcohol 72 hours prior to first dose and through follow-up visit.
• Must be willing to abstain from cannabis 72 hours prior to first dose and through follow-up visit.
• Must be willing to abstain from caffeine (including tea, coffee, chocolate) or grapefruit, Seville orange juice or other methyl xanthine containing foods (e.g. theophylline, theobromine, tea leaves, yerba mate, kola nuts and guarana berries) 72 hours prior to the first dose and through follow- up visit.
• Must have a body mass index (BMI) from 19 to 30 kg/m^2 (inclusive) at screening.
• Must be human immunodeficiency virus type 1 (HIV-1) antibody negative at screening.
• Must be hepatitis B (HBV) surface antigen negative at screening.
• Must be hepatitis C (HCV) antibody or RNA negative at screening.
• Male subjects must refrain from sperm donation from clinic admission, throughout the study period, and continuing for at least 90 days following the last dose of study drug.
• Subjects must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study drug.
• Must be willing to comply with contraception guidelines below Contraception:

The fetal risks associated with ANS-6637 are not known, but pre- clinical animal data demonstrate some risk. Subjects must agree not to become pregnant or impregnate a female. Females of childbearing potential must have a reproductive risk assessment done to determine the risk of undetectable pregnancy at study start [i.e. sexual and contraceptive history for 30 days preceding screening] pregnancy test at screening and baseline (Day 0). For the duration of the study, subject and their partners must practice two non-hormonal methods of birth control, having begun no less than 30 days, without interruption, prior to screening. They must continue to use both methods until 3 months after stopping the study drug. Two of the three methods of birth control listed below MUST be used, or an alternative combination offering very high efficacy, per the PI, in consultation with the Sponsor Medical Monitor may be considered:

• Male or female condoms [but not both] with a spermicide
• Diaphragm with a spermicide
• Intrauterine device (IUD)

If pregnancy is suspected or should occur, subjects must notify the study staff immediately.

• Must, in the opinion of the Investigator, be in good health based upon medical history and physical examination, and screening laboratory evaluations.
• Judged to be healthy based on medical history, physical examination, vital signs, and clinical laboratory tests at screening and Day 0: liver function tests (AST, ALT, Tbili) less than or equal to upper limit of normal [ULN], platelets (PLT) >150,000/ microliter, hemoglobin (Hgb) >13 g/dL (males); >12 g/dL (females), CK less than or equal to 2x ULN, Amylase/lipase 220 msec; QRS >120 msec; QTcF >450 msec; HR <40 beats per minute; second or third degree heart block.
• Have a history or family history of Long QT Syndrome, Brugada syndrome, Wolfe-Parkinson-White Syndrome, or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years.
• Have history of syncope, palpitations, unexplained dizziness or chronic nausea or headaches.
• Have an implanted defibrillator or pacemaker.
• Have a history of liver disease, including Gilbert's Disease.
• Any clinically significant electrolyte abnormality (outside of NIH nor