A First-in-Human, 2-Part, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Ascending Dose, and Food-Effect Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of VNT-101 Administered Orally to Healthy Adult Participants
A randomized, double-blind, placebo-controlled Phase 1 study conducted at a single center with approximately 78 healthy adults aged 18-59 years. Part 1 Single Ascending Dose (SAD) will enroll 48 participants into six cohorts (S1-S6) to receive single oral doses of VNT-101 (100-1500 mg) or placebo under fasting or fed (S5 only) conditions. Part 2 Multiple Ascending Dose (MAD) will enroll 30 participants into three cohorts (M1-M3) to receive multiple oral doses of VNT-101 (250-750 mg BID Days 1-5, QD Day 6) or placebo under fasting conditions. Dose escalation in both parts will proceed after Protocol Safety Review Team (PSRT) review. The primary objective for Part 1 is to evaluate the safety and tolerability of single ascending oral (SAD) doses of VNT-101 in healthy adult participants under either fasting or fed conditions. The primary objective for part 2 is to evaluate the safety and tolerability of multiple ascending oral (MAD) doses of VNT-101 in healthy adult participants.
• Provides written informed consent prior to the initiation of any trial procedures.
• Able to understand and agrees to comply with all planned trial procedures and be available for all study visits.
• Healthy, adult, male or female (of non-childbearing potential only\*), 18-59 years of age, inclusive, at the screening visit.
• \* Female participants of non-childbearing potential must be either surgically sterile (i.e., hysterectomy, bilateral tubal ligation, bilateral tubal occlusion \[hysteroscopic sterilization\], salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or post-menopausal, defined as spontaneous amenorrhea for at least a year, with follicle-stimulating hormone (FSH) in the post-menopausal range at Screening, based on the central laboratory ranges.
• Continuous non-smoker who has not used nicotine-, tobacco-, cannabis-, or cannabidiol-containing products\*\* prior to the first dosing based on participant self-reporting.
• \*\*The period before first dose is at least 3 months for tobacco and associated products and at least 60 days for cannabis and associated products.
• Body mass index (BMI)\>/=18.0 and \</= 30.0 kg/m\^2 at the screening visit.
• Medically healthy\*\*\* with no clinically significant medical history, physical examination, laboratory profiles, vital signs, and ECGs, as deemed by the Principal Investigator (PI) or designee,
• \*\*\*Including the following:
⁃ Supine diastolic blood pressure is \>/= 40 mmHg and \</= 90 mmHg at the screening visit.
⁃ Supine systolic blood pressure is \>/= 90 mmHg and \</= 140 mmHg at the screening visit.
⁃ Supine heart rate is \>/= 60 bpm and\</= 100 bpm at the screening visit.
⁃ QTcF interval is \</= 460 msec (males) and \</=470 msec (females) and has ECG findings considered normal or not clinically significant by the PI or designee at the screening visit.
⁃ Estimated creatinine clearance \>/= 80 mL/min based on the Cockroft-Gault equation and creatinine \<1.50 mg/dL at the screening visit.
⁃ Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is not greater than 1.1 times the upper limit of normal (ULN), as specified by the testing laboratory.
⁃ Other clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee.
• Must agree to refrain from using tanning salons, saunas, sunbathing, or prolonged sun exposure during participation in the study through the follow-up visit.
• Male participants must agree not to donate sperm during the study and for 90 days following the last administration of Study Product.
• Male participants must agree to use a medically accepted contraceptive regimen\*\*\*\* during participation and for 30 days after last administration of the study product or be vasectomized.
⁃ Acceptable methods of contraception include abstinence from intercourse with a female of childbearing potential or use of male condoms with spermicide or surgical sterilization (vasectomy) of participant at least 26 weeks before the Screening.