Single Ascending Dose Safety and Tolerability of NTS-104 Healthy Adults

Eligibility Criteria

• 1. Participants who provide written informed consent to participate in the study.
• 2. Healthy males and females between 18 and 65 years (inclusive) of age at the time of signing informed consent.
• 3. Body mass index (BMI) of 18 to 32 kg/m2 (inclusive) and weighing at least 50 kg at screening.
• 4. Participants in general good health in the opinion of the Investigator as determined by medical history; vital signs; and physical, neurological, and suicidal ideation examinations.
• 5. Blood pressure and heart rate within normal limits (blood pressure: systolic 90 to 140 mmHg and diastolic 50 to 90 mmHg; heart rate: 45 to 100 beats per minute) at screening and at admission on Day -1.
• 6. Female participants must have a negative serum pregnancy test at screening and at admission and be willing and able to use a medically acceptable method of birth control - Acceptable methods of birth control in this study must start one complete menstrual cycle (and at least 30 days) prior to the first day of dosing and continue until 4 weeks after the final follow-up visit.
• * Acceptable methods of birth control include abstinence, tubal ligation, bilateral tubal occlusion, progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable and implantable), combined hormonal contraception (i.e., estrogen- and progestogen-containing), IUS and IUD.
• * Female participants of non-childbearing potential are defined as either postmenopausal (evidence of menopause based on a combination of amenorrhea for at least one year confirmed with pre-admission serum follicle-stimulating hormone level \[\>30 IU/L\]), or surgical sterilization (evidence of hysterectomy and/or bilateral oophorectomy).
• * Male participants with a partner who might become pregnant must use reliable forms of contraception during the trial and 4 weeks afterward. Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method (condom).
• * The participant's female partner uses oral contraceptives (combined hormonal contraception), injectable progesterone or subdermal implants, and the male partner uses a barrier method (condom)
• 1. History of significant medical disorder that, in the opinion of the Investigator, contraindicates administration of the study medications.
• 2. Any active or current comorbidity with the exception of topical or allergic conditions treated with topical comedication and/or non-drowsy anti-allergic medication or acetaminophen
• 3. Any use of current comedication at admission or during the 30 days prior to enrollment with the exception of topical dermatological medication and/or non-drowsy anti-allergic medication or acetaminophen
• 4. Any acute illness (e.g., acute infection) within 72 hours of study drug administration, if considered of significance by the Investigator.
• 5. Any clinically significant abnormality in safety laboratory tests at screening or admission, in particular a screening TSH test
• 6. Positive human immunodeficiency virus, hepatitis B, or hepatitis C serology at screening.
• 7. Specifically, any history or current diagnosis of hepatic impairment at screening and Day - 1
• 8. Specifically, any history or current diagnosis of renal impairment at screening
• 9. Specifically, a history of type 1 diabetes mellitus or current type 2 diabetes.
• 10. Any abnormality on the neurological examination, at screening or enrollment
• 11. Positive Columbia-Suicide Severity Rating Scale (C-SSRS).
• 12. Participation in another clinical trial with drugs received within 3 months prior to dosing (calculated from the previous study's last dosing date).
• 13. Participant who is an active smoker and/or has smoked or used nicotine or nicotine- containing products (e.g., nicotine patch, gum, e-cigarettes) within the past 6 months before enrollment.
• 14. The use of ketogenic diets within 12 months prior to enrollment.
• 15. Electrocardiogram (ECG) with clinically significant findings recorded at screening or admission.
• 17. Positive coronavirus disease 2019 (COVID-19) test determined at screening and admission (nasal swab).
• 18. Known history of alcohol or drug abuse in the past 5 years. 19. Positive urinary drug or cotinine screen determined at screening and admission.
• 20. Positive serum alcohol screen determined during the screening period and on admission.
• 21. Any other condition, which in the Investigator's opinion, would not make the participant a good candidate for the study.
• 22. Blood donation of 500 mL (1 pint) or more: 56 days before the screening visit and until after the follow-up visit.
• 23. Plasma donation: 7 days before the screening visit and until after the follow-up visit.
• 24. Grapefruit, grapefruit juice, star fruit, pomegranate, and Seville oranges: 7 days before screening and until after the follow-up visit