An ascending, single and multiple dose(s), double-blind, randomized, placebo controlled study assessing the safety, tolerability, and pharmacokinetics of ov329 in healthy male and female participants

INTERVENTION: OV329 is a novel chemical compound identified as a potent GABA‐AT inhibitor. Its therapeutic component comprises a gamma‐amino butyric acid analog zwitterion, with the active pharmaceutical ingredient supplied as a hydrochloride salt. Study OV329‐22‐001 is a Phase 1, multi‐center, randomized, double‐blind, parallel, placebo‐controlled, two‐part study to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of OV329. This study is divided into sequential Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) segments. The SAD portion (Part A) precedes the MAD portion (Part B), with the latter initiated following a comprehensive review of all data from Part A. It is worth noting that Part B may commence before the completion of all planned cohorts in Part A. Prior to the onset of Part B, an amendment will be submitted to support the proposed dosing regimens, safety evaluations, and PK/PD assessments, if deemed necessary. Both Part A and Part B will enroll healthy adult males and non‐pregnant or non‐breastfeeding females. Each segment will comprise of multiple dosing cohorts, each defined by a specific dose. The Dose Review Committee (DRC) will assess safety, tolerability, PK, and Magnetic Resonance Spectroscopy (MRS) data for each cohort to determine subsequent dosing levels, particularly for Part B based on Day 30 data, which includes ophthalmologic assessments. Within each cohort of Part A and Part B, a sentinel group comprising two participants (one receiving active treatment and one receiving placebo) will be randomized and dosed ahead of the remaining participants. These individuals will undergo close monitoring for 48 hours post‐dose during the in‐unit phase of Part A (Day 3) and for 13 days (312 hours) during the inp CONDITION: Neurological ‐ Epilepsy rare seizure disorders ; ; rare seizure disorders SECONDARY OUTCOME: To characterize the PK of OV329 in healthy male and female participants after single (Part A)[PK parameters will be calculated using non‐compartmental methods for each participant. Descriptive statistics will be provided for the PK parameters for OV329 and potential major metabolites using appropriate summary statistics to be fully specified in the PK Analysis Plan (PK AP): ; Part A: Minimally, OV329 Cmax, Tmax, t1/2, AUClast, and AUCinf ; Single Dose Plasma PK (Day 1): ; Day 7 Plasma PK: OV329 plasma PK profile, including Cmax, tmax, AUC0‐24, AUClast, AUCinf, t1/2, accumulation ratio (RA) AUC0‐24, ] To characterize the PK of OV329 in healthy male and female participants after single (Part B)[PK parameters will be calculated using non‐compartmental methods for each participant. Descriptive statistics will be provided for the PK parameters for OV329 and potential major metabolites using appropriate summary statistics to be fully specified in the PK Analysis Plan (PK AP): ; Part B: Minimally, OV329 Cmax, Tmax, AUC0‐24, RA AUC0‐24, RA Cmax, and t1/2. ; Accumulation ratio (RA) AUC0‐24, RA Cma X(Part B) ; Urine PK: OV329 PK as data allow after single dose (Day 1, Part B) and on Day 7 (Part B) ; ] PRIMARY OUTCOME: To assess the safety and tolerability of single (Part A) oral doses of OV329 in healthy male and female participants[Treatment‐emergent adverse events (TEAEs), 12‐lead electrocardiograms (ECGs), vital signs, and clinical laboratory test results, physical, neurological, and ophthalmological examinations, and Columbia Suicide Severity Rating Scale (C‐SSRS); height (cm) manually recorded using height chart, weight (kg) using scale, BMI (calculated based on height and weight), systolic and diastolic blood pressure using a sphygmomanometer, heart rate (beats per minute) using portable vital signs monitor, respiratory rate (breaths/minute) manually counted and temperature (degrees Celsius) using a thermometer.; Hematology ‐ taken from blood ; Erythrocytes ; Hemoglobin; Hematocrit; Red blood cell indices; Mean corpuscular volume reticulocytes; Ret. mean corpuscular hemoglobin; Ret. corpuscular hemoglobin content; Reticulocyte distribution width; White blood cell count and differential; Neutrophils, segmented; Lymphocytes; Monocytes; Eosinophils; Basophils; Platelets; Mean platelet volume; Leukocyte esterase; Coagulation ‐ taken from blood ; INR; aPTT; Urinalysis ‐ taken from urine:; pH; Protein; Glucose; Ketones; Bilirubin; Nitrite; Urobilinogen; Urine toxicology; Clinical Chemistry ‐ taken from blood:; Sodium; Potassium; Total bilirubin; Direct bilirubin; ; Alkaline phosphatase; Alanine aminotransferase (ALT); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); Creatinine; ; Calcium; Phosphate; Glucose, fasting and non‐fasting; Albumin; Protein; Carbon dioxide; Magnesium; Chloride; Blood urea nitrogen (BUN); Part A: Single Ascending Dose; Screening period: Day‐28 to Day‐2 ; Treatment period: single administration on Day 1; Follow‐up period: Day 1 to Day 7 ; ] To assess the safety and tolerability of single (Part B) oral doses of OV329 in healthy male and female participants[Treatment‐emergent adverse events (TEAEs), 12‐lead electrocardiograms (ECGs), vital signs, and clinical laboratory test results, physical, neurological, and ophthalmological examinations, and Columbia Suicide Severity Rating Scale (C‐SSRS); height (cm) manually recorded using height chart, weight (kg) using scale, BMI (calculated based on height and weight), systolic and diastolic blood pressure using a sphygmomanometer, heart rate (beats per minute) using portable vital signs monitor, respiratory rate (breaths/minute) manually counted and temperature (degrees Celsius) using a thermometer.; Hematology ‐ taken from blood ; Erythrocytes ; Hemoglobin; Hematocrit; Red blood cell indices; Mean corpuscular volume reticulocytes; Ret. mean corpuscular hemoglobin; Ret. corpuscular hemoglobin content; Reticulocyte distribution width; White blood cell count and differential; Neutrophils, segmented; Lymphocytes; Monocytes; Eosinophils; Basophils; Platelets; Mean platelet volume; Leukocyte esterase; Coagulation ‐ taken from blood ; INR; aPTT; Urinalysis ‐ taken from urine:; pH; Protein; Glucose; Ketones; Bilirubin; Nitrite; Urobilinogen; Urine toxicology; Clinical Chemistry ‐ taken from blood:; Sodium; Potassium; Total bilirubin; Direct bilirubin; ; Alkaline phosphatase; Alanine aminotransferase (ALT); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); Creatinine; ; Calcium; Phosphate; Glucose, fasting and non‐fasting; Albumin; Protein; Carbon dioxide; Magnesium; Chloride; Blood urea nitrogen (BUN) Screening period: from Day ‐28 to Day‐2 ; Treatment period: repeated once daily administration for 7 days ; Follow‐up period: from Day 7 to Day 30 +/‐ 5 days; ] INCLUSION CRITERIA: Participants are eligible to be included in the study only if they meet all the following criteria and none of the exclusion criteria: 1. Participant must give written informed consent prior to participation in the study. 2. Participant agrees not to post any of the participant's personal or medical data or information related to the study on any website, message board(s), online groups, or social media website (e.g. Facebook, Instagram, Twitter etc.) until notified that the study is completed. 3. Participant must be willing and able to comply with the study procedures (including diet) and visit schedules and must be able to follow verbal and written instructions. 4. Male and female participants aged 18 to 55 years at the time of informed consent. 5. Weighs at least 50 kg and body mass inde X(BMI) greater than or equal to 18.0 and less than 35.0 kg/m2 at screening. 6. Continuous nonsmoker who has not used nicotine containing products (includi