A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered PRN2246 in Healthy Volunteers

INTERVENTION: Placebo‐controlled, First‐In‐Human study assessing the safety, tolerability, and pharmacokinetics of PRN2246. Part A Up to 48 participants in 5 cohorts will take part in Part A of the study. Participants in Part A will receive a single dose of PRN2246 liquid formulation. Planned doses in Part A are Cohort A1 7.5mg, Cohort A2 15mg, Cohort A3 30mg, Cohort A4 60mg, and Cohort A5 120mg.. Participants in Part A will receive the liquid formulation whilst fasting with the exception of 1 cross over cohort that will receive the liquid formulation administered with and without food (with up to a 7 day washout between doses). Part B Up to 50 participants in up to 5 cohorts will take part in Part B of the study. Participants in Part B of the study will receive one dose of PRN2246 liquid formulation per day for 10 days (doses to be assigned based on data from Part A). Planned doses in Part B are Cohort B1 7.5mg, Cohort B2 15mg, Cohort B3 30mg, Cohort B4 60mg, Cohort B5 120mg. Part C Up to 8 participants (two groups of 4 participants each) will take part in Part C of the study. Part C will be open label and participants will receive one single 120mg dose of PRN2246 liquid formulation. Dose escalation to subsequent cohorts in Part A and B will occur following review of the safety, tolerability, and available PK/PD information from the previous dose level. Dose levels may be adjusted based on emerging safety, tolerability, and PK data. Study subjects will be domiciled during the study and adherence to the dosing regimen will be monitored by study staff observations, notes. Accurate dose and accountability will be checked before and after dosing. CONDITION: Immune‐mediated neurologic disorders PRIMARY OUTCOME: Safety and tolerability, including the assessment of physical examinations, ECGs, vital signs, clinical laboratory results, and adverse events SECONDARY OUTCOME: Nil INCLUSION CRITERIA: 1. Healthy adult male and/or female volunteers, 18 to 55 years of age (inclusive) at the time of screening 2. Body mass index (BMI) greater than or equal to 18 (kg/m2) and less than or equal to 30.5 (kg/m2), and a minimum body weight of 45kg at screening 3. Able to participate and comply with all study procedures and restrictions, and willing to provide written informed consent to participate in the study 4. Male volunteers with female partners of child‐bearing potential must be willing to practice true abstinence or use two highly effective methods of contraception (including one barrier method) from Day 1 until 90 days after their last dose of study treatment 5. Female volunteers must be surgically sterile or post‐menopausal 6. Negative urine drug and alcohol breath testing at screening and check‐in (Day 1)