A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GNS-3545 in Healthy Participants

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose, Multiple Ascending Dose, and Food-effect Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GNS-3545 in Healthy Adult Subjects

This is a randomized, double-blind, placebo-controlled Phase 1 study of SAD (Part 1) and MAD (Part 2) of orally administered GNS-3545 in healthy adult subjects. The food effect will be assessed in one cohort in Part 1.

Inclusion Criteria:

• Healthy, adult, male or female (of non-childbearing potential only), 18-55 years of age
• Male subjects must follow protocol specified contraception guidance
• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing
• BMI ≥ 18.0 and ≤ 32.0 kg/m2 at the screening visit and body weight of ≥ 50 kg
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, or vital signs, as deemed by the PI or designee
• No ECG findings of clinical significance as judged by the PI or qualified designee
• Understands the study procedures in the ICF and be willing and able to comply with the protocol

Exclusion Criteria:

• Is mentally or legally incapacitated or has significant emotional problems
• History or presence of clinically significant medical or psychiatric conditions
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study
• Surgical procedure or Administration of a live vaccination within 30 days prior to the first dose of the study drug
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing
• History or presence of hepatic impairment
• History or presence of significant cardiovascular conditions or risk factors
• Subjects with a higher risk of adverse events in the setting of blood pressure decreases
• History or presence of hypersensitivity to compounds related to the study drug excipients
• Allergy to non-latex band aids, adhesive dressing, or medical tape
• Female subjects of childbearing potential or Female subject with a positive pregnancy test or who is lactating
• Positive urine drug or serum alcohol results
• Positive results at the screening visit for HIV, HBsAg, or HCV, or a clinically significant history of infection within 3 months prior to screening
• Inability or unwillingness to avoid use of medications, supplements, or substances that may affect CYP enzymes, drug transporters, blood pressure, or QT/QTc interval within the specified washout periods prior to dosing
• Has been on a diet incompatible with the on-study diet, or unable to swallow multiple tablets by mouth
• Has donated or lost more than 500 mL of blood within 56 days prior to the first dosing, or Plasma donation within 7 days prior to the first dosing
• Subjects with dietary restrictions that would prevent subjects from consuming a high-fat/high-calorie meal
• Participation in another clinical study within 30 days or 5 half-lives of the product prior to the first dosing
• Any reason determined by the PI or designee, in their opinion, that would prevent the subject's participation in the study