Part 1: Multiple Ascending Dose Study (MAD): Open-label, ascending dose given once daily for 14 days in healthy volunteers. The study will enroll 3 cohorts (dose levels) sequentially, each with 10 participants (5F/5M) per cohort, so that a minimum of 8 study participants (4F/4M) per cohort complete all study procedures. Participants will follow a diet low in soy isoflavones for 7 days before, during and 7 days after treatment and will be required to fast at least 10 hours before the first, sixth and last dose. BIO 300 Oral Suspension will be administered starting on day 1. The first cohort, Cohort 1, will be administered BIO 300 Oral Suspension at 2000 mg/day once daily for 14 days. If dose escalation criteria are met, Cohort 2 will be administered 3000 mg/day, and similarly if dose escalation criteria are met following Cohort 2, then Cohort 3 will be administered 4000 mg/day. Following the completion of Cohort 3, there will be an option to enroll a fourth cohort at a higher or lower dose depending on the outcomes of the first three cohorts. Participants will be administered BIO 300 Oral Suspension daily during their scheduled clinic visits. Participants will remain in the clinic 12 hours after the first dose, sixth dose and last dose and for observations and blood sample collection for clinical lab assessment, pharmacokinetics (PK) and pharmacodynamics (PD). On the day 1, 6 and 14, participants will remain fasted after dosing for 4 hours until provided a standardized low soy meal after the 4 hour blood draw and after the 8 hour blood draw. Blood sampling and/or observations will be performed on dosing days 1-14 as described in the schedule of events. Participants will return to the clinic on days 15, 16 and 21 after their final dose for blood sampling and/or observations as detailed in the schedule of events. Safety data will be reviewed after the completion of each cohort to approve dose escalation. At the conclusion of all three cohorts, all data will be analyzed to assess safety, PK and PD. If the optional fourth cohort is enrolled, all data (safety, PK and PD) from the fourth cohort will be analyzed at the conclusion of the cohort.
Part 2: Food Effect Study: Following the MAD study, an open-label, single-dose food effect study in healthy volunteers will be conducted. The study will enroll 16 participants (8F/8M), so that a minimum of 12 study participants (6F/6M) complete all study procedures. Study participants will be randomized 1:1 into two cohorts. Cohort 1 will be administered a single BIO 300 Oral Suspension dose under fasted conditions and Cohort 2 will be administered a single BIO 300 Oral Suspension dose under fed conditions. After a 7 day washout period, participants in cohort 1 will receive another dose of BIO 300 Oral Suspension under fed conditions and participants in cohort 2 will receive another dose of BIO 300 Oral Suspension under fasted conditions (cross over design). All participants will follow a diet low in soy isoflavones for 7 days before dosing, during the washout period and for 7 days after dosing. The planned BIO 300 Oral Suspension dose used in this study will be 3000 mg, however this is subject to change following safety and PK data review following the completion of the MAD study above. For fasted dosing, participants will be required to fast for at least 10 hours prior to dosing and for 4 hours after dosing. For fed dosing, participants will receive an FDA-approved high-fat meal with no substitutions (800-1000 calories; approximately 50% of calories derived from fat) following an overnight fast of at least 10 hours. The entire meal will be consumed within 30 minutes, dosing will begin 30 minutes after starting the meal, and participants will fast for 4 hours after dosing. All participants will remain in the clinic 12 hours after each dose for observations and blood sample collection for clinical lab assessment, and PK. All participants will remain fasted (fasted cohort) or fast (fed cohort) after dosing for 4 hours until provided a standardized low soy meal after the 4 hour blood draw and after the 8 hour blood draw. Participants will return to the clinic on day 2 and 3 after dosing for blood sampling and/or observations as detailed in the schedule of events (day 10 and 11 after the second dose). At the conclusion of the study, data will be analyzed from both cohorts to determine safety and PK.
