This is a randomized, , placebo-controlled, Phase 1, single-dose, dose-escalation study to assess the safety, tolerability, and PK of IV NTS-104 in healthy participants. The study is composed of a screening period, a treatment day, and a follow-up period. The study will enroll 4 cohorts with 8 participants in each cohort. Participants in each cohort will be randomized 3:1 to receive either a single IV administration of NTS-104 or placebo. Cohort 1 will be administered 0.8 mg/kg (Cohort 1) with proposed subsequent doses of 4 mg/kg (Cohort 2), 8 mg/kg (Cohort 3), and 16 mg/kg (Cohort 4). Two additional cohorts of 8 participants each, Cohorts 5 and 6, may be enrolled if the human equivalent dose to the no-observed-adverse-effect level (NOAEL) dose in rats is not reached or if exposure limits are not exceeded in the first 4 cohorts. Each cohort will start with a sentinel pair of participants, with 1 participant assigned to NTS-104 Tris (Arm 1) and 1 participant randomized to placebo (Arm 2). If there are no safety concerns identified at 48 hours, the remainder of the cohort will be dosed, with 5 participants randomized to NTS-104 Tris (Arm 1) and 1 participant assigned to placebo (Arm 2).
NTS-104 TRIS will be administered as a single intravenous dose to healthy subjects at doses of 0.8, 4, 8 and 16 mg/kg in 4 Cohorts. Each cohort of 8 subjects will begin with dosing 2 sentinel subjects with one being given the investigational product and one the placebo. If no safety issues arise, dosing the remaining subjects in the cohort will begin. A Safety Review Committee will review the safety and pharmacokinetic data before approving escalation to the next dose level.