Trial Outcomes & Findings for BIO 300 Oral Powder Safety and Pharmacokinetics (NCT NCT04650555)

NCT ID: NCT04650555

Last Updated: 2024-05-03

Results Overview

Evaluate the safety of single and multiple dose BIO 300 Oral Powder administration

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

Day 1 up to 1 week for Single Ascending Dose and Day 1 up to 2 weeks for Multiple Single Dose

Results posted on

2024-05-03

Participant Flow

Participant milestones

Participant milestones
Measure	Single Ascending Dose Cohort 1 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Overall Study STARTED	6	6	6	6	10
Overall Study COMPLETED	6	6	5	6	8
Overall Study NOT COMPLETED	0	0	1	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

BIO 300 Oral Powder Safety and Pharmacokinetics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Ascending Dose Cohort 1 n=6 Participants 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=6 Participants 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=6 Participants 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Participants Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=10 Participants Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Total n=34 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	37 years n=7 Participants	40 years n=5 Participants	48 years n=4 Participants	46 years n=21 Participants	45 years n=8 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants	18 Participants n=8 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants	16 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	10 Participants n=21 Participants	33 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	8 Participants n=21 Participants	29 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants	10 participants n=21 Participants	34 participants n=8 Participants

PRIMARY outcome

Timeframe: Day 1 up to 1 week for Single Ascending Dose and Day 1 up to 2 weeks for Multiple Single Dose

Population: No adverse events were reported for the Single Ascending Dose Cohort 1

Evaluate the safety of single and multiple dose BIO 300 Oral Powder administration

Outcome measures

Outcome measures
Measure	Single Ascending Dose Cohort 1 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=5 Number of Adverse Events 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=4 Number of Adverse Events 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Number of Adverse Events Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=26 Number of Adverse Events Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Adverse Events Related to BIO 300 Oral Powder Unrelated Adverse Event	—	0 Number of Adverse Events	0 Number of Adverse Events	1 Number of Adverse Events	1 Number of Adverse Events
Adverse Events Related to BIO 300 Oral Powder Dose Limiting Toxicities	—	0 Number of Adverse Events	0 Number of Adverse Events	0 Number of Adverse Events	0 Number of Adverse Events
Adverse Events Related to BIO 300 Oral Powder Unlikely Treatment-Related Adverse Events	—	1 Number of Adverse Events	0 Number of Adverse Events	0 Number of Adverse Events	2 Number of Adverse Events
Adverse Events Related to BIO 300 Oral Powder Possibly Treatment-Related Adverse Events	—	0 Number of Adverse Events	0 Number of Adverse Events	3 Number of Adverse Events	7 Number of Adverse Events
Adverse Events Related to BIO 300 Oral Powder Probably Treatment-Related Adverse Events	—	4 Number of Adverse Events	4 Number of Adverse Events	0 Number of Adverse Events	15 Number of Adverse Events
Adverse Events Related to BIO 300 Oral Powder Definitely Treatment-Related Adverse Events	—	0 Number of Adverse Events	0 Number of Adverse Events	2 Number of Adverse Events	1 Number of Adverse Events

PRIMARY outcome

Timeframe: Day 1 up to 1 week after the last dose for Single Ascending Dose and Multiple Single Dose Cohorts

Measurement of the average QTc interval with Fridericia's correction (completed in triplicate at each timepoint)

Outcome measures

Outcome measures
Measure	Single Ascending Dose Cohort 1 n=6 Participants 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=6 Participants 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=6 Participants 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Participants Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=10 Participants Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Change in ECG QTc Interval Screening	407 milliseconds Standard Deviation 9.3	402 milliseconds Standard Deviation 19.3	416 milliseconds Standard Deviation 21.8	415 milliseconds Standard Deviation 18.7	413 milliseconds Standard Deviation 13.3
Change in ECG QTc Interval 4 Hours Post First Dose	412 milliseconds Standard Deviation 9.6	407 milliseconds Standard Deviation 16.5	419 milliseconds Standard Deviation 27.8	420 milliseconds Standard Deviation 16.3	417 milliseconds Standard Deviation 7.4
Change in ECG QTc Interval 24 Hours Post First Dose	407 milliseconds Standard Deviation 11.3	400 milliseconds Standard Deviation 11.2	402 milliseconds Standard Deviation 26.7	404 milliseconds Standard Deviation 41.7	413 milliseconds Standard Deviation 9.9
Change in ECG QTc Interval 1 Week Post Last Dose	408 milliseconds Standard Deviation 12.4	401 milliseconds Standard Deviation 18.3	416 milliseconds Standard Deviation 36.3	414 milliseconds Standard Deviation 12.6	415 milliseconds Standard Deviation 9.0

PRIMARY outcome

Timeframe: Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose

Population: Participants in the single ascending dose study were assessed on days 3 and 7 and participants in the multiple dose study were assessed on days 3, 6 and 13

Monitoring of blood serum levels of albumin and total protein (all reported as g/dL)

Outcome measures

Outcome measures
Measure	Single Ascending Dose Cohort 1 n=6 Participants 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=6 Participants 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=6 Participants 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Participants Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=8 Participants Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Change in Clinical Laboratory Values Albumin Day 3	4.483 g/dL Standard Deviation 0.204	4.433 g/dL Standard Deviation 0.393	4.333 g/dL Standard Deviation 0.367	4.550 g/dL Standard Deviation 0.187	4.225 g/dL Standard Deviation 0.349
Change in Clinical Laboratory Values Albumin Day 6	—	—	—	—	4.475 g/dL Standard Deviation 0.249
Change in Clinical Laboratory Values Albumin Day 7	4.233 g/dL Standard Deviation 0.216	4.283 g/dL Standard Deviation 0.279	4.440 g/dL Standard Deviation 0.241	4.517 g/dL Standard Deviation 0.117	—
Change in Clinical Laboratory Values Albumin Day 13	—	—	—	—	4.475 g/dL Standard Deviation 0.306
Change in Clinical Laboratory Values Total Protein Day 3	6.667 g/dL Standard Deviation 0.344	6.833 g/dL Standard Deviation 0.638	6.500 g/dL Standard Deviation 0.369	6.650 g/dL Standard Deviation 0.547	6.363 g/dL Standard Deviation 0.444
Change in Clinical Laboratory Values Total Protein Day 6	—	—	—	—	6.788 g/dL Standard Deviation 0.348
Change in Clinical Laboratory Values Total Protein Day 7	6.417 g/dL Standard Deviation 0.331	6.850 g/dL Standard Deviation 0.619	6.520 g/dL Standard Deviation 0.438	6.717 g/dL Standard Deviation 0.454	—
Change in Clinical Laboratory Values Total Protein Day 13	—	—	—	—	6.550 g/dL Standard Deviation 0.518

PRIMARY outcome

Timeframe: Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose

Population: Analyzed on Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose

Monitoring of blood serum levels of bicarbonate, chloride, potassium, and sodium (all reported as mEq/L)

Outcome measures

Outcome measures
Measure	Single Ascending Dose Cohort 1 n=6 Participants 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=6 Participants 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=6 Participants 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Participants Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=8 Participants Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Change in Clinical Laboratory Values Bicarbonate Day 3	26.833 mEq/L Standard Deviation 1.722	26.167 mEq/L Standard Deviation 0.753	27.167 mEq/L Standard Deviation 2.401	27.500 mEq/L Standard Deviation 1.049	23.875 mEq/L Standard Deviation 2.850
Change in Clinical Laboratory Values Bicarbonate Day 6	—	—	—	—	23.750 mEq/L Standard Deviation 1.165
Change in Clinical Laboratory Values Bicarbonate Day 7	26.500 mEq/L Standard Deviation 1.871	27.500 mEq/L Standard Deviation 1.761	29.000 mEq/L Standard Deviation 0.707	28.667 mEq/L Standard Deviation 1.751	—
Change in Clinical Laboratory Values Bicarbonate Day 13	—	—	—	—	23.125 mEq/L Standard Deviation 1.246
Change in Clinical Laboratory Values Chloride Day 3	104.5 mEq/L Standard Deviation 2.429	104.0 mEq/L Standard Deviation 1.549	104.7 mEq/L Standard Deviation 0.816	103.5 mEq/L Standard Deviation 0.837	105.5 mEq/L Standard Deviation 1.927
Change in Clinical Laboratory Values Chloride Day 6	—	—	—	—	103.8 mEq/L Standard Deviation 2.252
Change in Clinical Laboratory Values Chloride Day 7	104.3 mEq/L Standard Deviation 1.366	104.5 mEq/L Standard Deviation 1.761	104.2 mEq/L Standard Deviation 1.095	104.8 mEq/L Standard Deviation 2.317	—
Change in Clinical Laboratory Values Chloride Day 13	—	—	—	—	105.1 mEq/L Standard Deviation 0.835
Change in Clinical Laboratory Values Potassium Day 3	4.417 mEq/L Standard Deviation 0.271	4.500 mEq/L Standard Deviation 0.141	4.617 mEq/L Standard Deviation 0.306	4.400 mEq/L Standard Deviation 0.303	4.288 mEq/L Standard Deviation 0.318
Change in Clinical Laboratory Values Potassium Day 6	—	—	—	—	4.413 mEq/L Standard Deviation 0.336
Change in Clinical Laboratory Values Potassium Day 7	4.217 mEq/L Standard Deviation 0.279	4.483 mEq/L Standard Deviation 0.306	4.580 mEq/L Standard Deviation 0.460	4.233 mEq/L Standard Deviation 0.151	—
Change in Clinical Laboratory Values Potassium Day 13	—	—	—	—	4.288 mEq/L Standard Deviation 0.155
Change in Clinical Laboratory Values Sodium Day 3	140.7 mEq/L Standard Deviation 1.966	139.5 mEq/L Standard Deviation 1.225	140.7 mEq/L Standard Deviation 0.816	140.2 mEq/L Standard Deviation 1.835	140.0 mEq/L Standard Deviation 1.414
Change in Clinical Laboratory Values Sodium Day 6	—	—	—	—	139.5 mEq/L Standard Deviation 1.414
Change in Clinical Laboratory Values Sodium Day 7	140.0 mEq/L Standard Deviation 1.265	139.2 mEq/L Standard Deviation 1.472	139.2 mEq/L Standard Deviation 1.304	142.3 mEq/L Standard Deviation 2.066	—
Change in Clinical Laboratory Values Sodium Day 13	—	—	—	—	140.1 mEq/L Standard Deviation 1.727

PRIMARY outcome

Timeframe: Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose

Population: Analyzed Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose

Monitoring of blood serum levels of bilirubin (total and direct), BUN, calcium, cholesterol (total), creatinine, HDL, glucose, magnesium, phosphorous, triglycerides, and uric acid (all reported as mg/dL)

Outcome measures

Outcome measures
Measure	Single Ascending Dose Cohort 1 n=6 Participants 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=6 Participants 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=6 Participants 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Participants Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=8 Participants Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Change in Clinical Laboratory Values Total Bilirubin Day 3	0.467 mg/dL Standard Deviation 0.308	0.417 mg/dL Standard Deviation 0.117	0.333 mg/dL Standard Deviation 0.137	0.650 mg/dL Standard Deviation 0.501	0.613 mg/dL Standard Deviation 0.394
Change in Clinical Laboratory Values Total Bilirubin Day 6	—	—	—	—	0.500 mg/dL Standard Deviation 0.185
Change in Clinical Laboratory Values Total Bilirubin Day 7	0.483 mg/dL Standard Deviation 0.331	0.583 mg/dL Standard Deviation 0.417	0.340 mg/dL Standard Deviation 0.167	0.400 mg/dL Standard Deviation 0.141	—
Change in Clinical Laboratory Values Total Bilirubin Day 13	—	—	—	—	0.563 mg/dL Standard Deviation 0.307
Change in Clinical Laboratory Values Direct Bilirubin Day 3	0.200 mg/dL Standard Deviation 0	0.200 mg/dL Standard Deviation 0	0.200 mg/dL Standard Deviation 0	0.200 mg/dL Standard Deviation 0	0.200 mg/dL Standard Deviation 0
Change in Clinical Laboratory Values Direct Bilirubin Day 6	—	—	—	—	0.200 mg/dL Standard Deviation 0
Change in Clinical Laboratory Values Direct Bilirubin Day 7	0.200 mg/dL Standard Deviation 0	0.200 mg/dL Standard Deviation 0	0.200 mg/dL Standard Deviation 0	0.200 mg/dL Standard Deviation 0	—
Change in Clinical Laboratory Values Direct Bilirubin Day 13	—	—	—	—	0.200 mg/dL Standard Deviation 0
Change in Clinical Laboratory Values BUN Day 3	18.00 mg/dL Standard Deviation 3.46	13.33 mg/dL Standard Deviation 2.94	14.83 mg/dL Standard Deviation 4.62	13.50 mg/dL Standard Deviation 4.51	11.88 mg/dL Standard Deviation 3.09
Change in Clinical Laboratory Values BUN Day 6	—	—	—	—	12.00 mg/dL Standard Deviation 2.83
Change in Clinical Laboratory Values BUN Day 7	16.67 mg/dL Standard Deviation 4.23	14.50 mg/dL Standard Deviation 2.88	14.20 mg/dL Standard Deviation 5.85	13.83 mg/dL Standard Deviation 4.26	—
Change in Clinical Laboratory Values BUN Day 13	—	—	—	—	11.63 mg/dL Standard Deviation 3.82
Change in Clinical Laboratory Values Calcium Day 3	9.73 mg/dL Standard Deviation 0.37	9.38 mg/dL Standard Deviation 0.32	9.27 mg/dL Standard Deviation 0.23	9.72 mg/dL Standard Deviation 0.33	9.25 mg/dL Standard Deviation 0.34
Change in Clinical Laboratory Values Calcium Day 6	—	—	—	—	9.60 mg/dL Standard Deviation 0.19
Change in Clinical Laboratory Values Calcium Day 7	9.47 mg/dL Standard Deviation 0.14	9.37 mg/dL Standard Deviation 0.26	9.18 mg/dL Standard Deviation 0.37	9.50 mg/dL Standard Deviation 0.32	—
Change in Clinical Laboratory Values Calcium Day 13	—	—	—	—	9.36 mg/dL Standard Deviation 0.30
Change in Clinical Laboratory Values Cholesterol Day 3	200 mg/dL Standard Deviation 43	181 mg/dL Standard Deviation 23	158 mg/dL Standard Deviation 19	210 mg/dL Standard Deviation 44	178 mg/dL Standard Deviation 23
Change in Clinical Laboratory Values Cholesterol Day 6	—	—	—	—	193 mg/dL Standard Deviation 22
Change in Clinical Laboratory Values Cholesterol Day 7	195 mg/dL Standard Deviation 34	180 mg/dL Standard Deviation 33	173 mg/dL Standard Deviation 32	213 mg/dL Standard Deviation 49	—
Change in Clinical Laboratory Values Cholesterol Day 13	—	—	—	—	177 mg/dL Standard Deviation 26
Change in Clinical Laboratory Values Creatinine Day 3	0.905 mg/dL Standard Deviation 0.182	0.943 mg/dL Standard Deviation 0.154	0.883 mg/dL Standard Deviation 0.180	0.900 mg/dL Standard Deviation 0.127	0.944 mg/dL Standard Deviation 0.116
Change in Clinical Laboratory Values Creatinine Day 6	—	—	—	—	1.030 mg/dL Standard Deviation 0.099
Change in Clinical Laboratory Values Creatinine Day 7	0.873 mg/dL Standard Deviation 0.147	1.028 mg/dL Standard Deviation 0.150	0.954 mg/dL Standard Deviation 0.212	0.980 mg/dL Standard Deviation 0.131	—
Change in Clinical Laboratory Values Creatinine Day 13	—	—	—	—	1.043 mg/dL Standard Deviation 0.094
Change in Clinical Laboratory Values HDL Day 3	52 mg/dL Standard Deviation 11	55 mg/dL Standard Deviation 15	52 mg/dL Standard Deviation 10	69 mg/dL Standard Deviation 21	49 mg/dL Standard Deviation 14
Change in Clinical Laboratory Values HDL Day 6	—	—	—	—	55 mg/dL Standard Deviation 15
Change in Clinical Laboratory Values HDL Day 7	52 mg/dL Standard Deviation 9	54 mg/dL Standard Deviation 16	56 mg/dL Standard Deviation 9	71 mg/dL Standard Deviation 23	—
Change in Clinical Laboratory Values HDL Day 13	—	—	—	—	52 mg/dL Standard Deviation 17
Change in Clinical Laboratory Values Glucose Day 3	95.2 mg/dL Standard Deviation 8.0	89.7 mg/dL Standard Deviation 7.3	90.7 mg/dL Standard Deviation 6.5	90.2 mg/dL Standard Deviation 8.8	96.3 mg/dL Standard Deviation 5.8
Change in Clinical Laboratory Values Glucose Day 6	—	—	—	—	93.6 mg/dL Standard Deviation 5.2
Change in Clinical Laboratory Values Glucose Day 7	101.5 mg/dL Standard Deviation 10.0	92.3 mg/dL Standard Deviation 2.7	97.0 mg/dL Standard Deviation 12.1	105.8 mg/dL Standard Deviation 40.8	—
Change in Clinical Laboratory Values Glucose Day 13	—	—	—	—	93.4 mg/dL Standard Deviation 4.7
Change in Clinical Laboratory Values Magnesium Day 3	2.10 mg/dL Standard Deviation 0.11	2.05 mg/dL Standard Deviation 0.14	2.07 mg/dL Standard Deviation 0.12	1.90 mg/dL Standard Deviation 0.17	1.98 mg/dL Standard Deviation 0.10
Change in Clinical Laboratory Values Magnesium Day 6	—	—	—	—	2.05 mg/dL Standard Deviation 0.17
Change in Clinical Laboratory Values Magnesium Day 7	2.02 mg/dL Standard Deviation 0.12	2.12 mg/dL Standard Deviation 0.10	2.06 mg/dL Standard Deviation 0.11	1.98 mg/dL Standard Deviation 0.12	—
Change in Clinical Laboratory Values Magnesium Day 13	—	—	—	—	2.06 mg/dL Standard Deviation 0.09
Change in Clinical Laboratory Values Phosphorous Day 3	3.58 mg/dL Standard Deviation 0.37	3.62 mg/dL Standard Deviation 0.45	3.75 mg/dL Standard Deviation 0.41	3.52 mg/dL Standard Deviation 0.34	3.14 mg/dL Standard Deviation 0.36
Change in Clinical Laboratory Values Phosphorous Day 6	—	—	—	—	3.49 mg/dL Standard Deviation 0.34
Change in Clinical Laboratory Values Phosphorous Day 7	3.62 mg/dL Standard Deviation 0.53	3.68 mg/dL Standard Deviation 0.42	3.70 mg/dL Standard Deviation 0.49	3.68 mg/dL Standard Deviation 0.62	—
Change in Clinical Laboratory Values Phosphorous Day 13	—	—	—	—	0.39 mg/dL Standard Deviation 0.54
Change in Clinical Laboratory Values Triglycerides Day 3	80.2 mg/dL Standard Deviation 43.3	104.2 mg/dL Standard Deviation 91.0	80.5 mg/dL Standard Deviation 37.5	85.5 mg/dL Standard Deviation 30.6	101.9 mg/dL Standard Deviation 38.8
Change in Clinical Laboratory Values Triglycerides Day 6	—	—	—	—	98.6 mg/dL Standard Deviation 23.3
Change in Clinical Laboratory Values Triglycerides Day 7	71.3 mg/dL Standard Deviation 22.1	117.3 mg/dL Standard Deviation 107.0	79.2 mg/dL Standard Deviation 44.5	80.5 mg/dL Standard Deviation 39.7	—
Change in Clinical Laboratory Values Triglycerides Day 13	—	—	—	—	89.8 mg/dL Standard Deviation 20.6
Change in Clinical Laboratory Values Uric Acid Day 3	5.25 mg/dL Standard Deviation 1.08	4.62 mg/dL Standard Deviation 1.26	4.48 mg/dL Standard Deviation 1.16	5.07 mg/dL Standard Deviation 1.38	5.20 mg/dL Standard Deviation 1.50
Change in Clinical Laboratory Values Uric Acid Day 6	—	—	—	—	5.21 mg/dL Standard Deviation 1.55
Change in Clinical Laboratory Values Uric Acid Day 7	5.13 mg/dL Standard Deviation 1.09	5.30 mg/dL Standard Deviation 1.89	4.10 mg/dL Standard Deviation 0.73	5.08 mg/dL Standard Deviation 1.24	—
Change in Clinical Laboratory Values Uric Acid Day 13	—	—	—	—	5.20 mg/dL Standard Deviation 1.60

PRIMARY outcome

Timeframe: Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose

Population: Analyzed day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose

Monitoring of blood serum levels of alkaline phosphatase, ALT, amylase, AST, LDH, and lipase (all reported as IU/L)

Outcome measures

Outcome measures
Measure	Single Ascending Dose Cohort 1 n=6 Participants 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=6 Participants 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=6 Participants 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Participants Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=8 Participants Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Change in Clinical Laboratory Values ALP Day 3	74.2 IU/L Standard Deviation 18.1	66.7 IU/L Standard Deviation 13.9	64.2 IU/L Standard Deviation 18.8	62.8 IU/L Standard Deviation 21.4	59.5 IU/L Standard Deviation 15.5
Change in Clinical Laboratory Values ALP Day 6	—	—	—	—	60.3 IU/L Standard Deviation 16.2
Change in Clinical Laboratory Values ALP Day 7	69.5 IU/L Standard Deviation 14.7	69.0 IU/L Standard Deviation 17.3	68.0 IU/L Standard Deviation 21.1	52.5 IU/L Standard Deviation 29.7	—
Change in Clinical Laboratory Values ALP Day 13	—	—	—	—	59.4 IU/L Standard Deviation 18.6
Change in Clinical Laboratory Values ALT Day 3	18.2 IU/L Standard Deviation 5.7	21.2 IU/L Standard Deviation 18.6	15.2 IU/L Standard Deviation 3.2	16.2 IU/L Standard Deviation 9.5	17.6 IU/L Standard Deviation 5.5
Change in Clinical Laboratory Values ALT Day 6	—	—	—	—	18.4 IU/L Standard Deviation 4.1
Change in Clinical Laboratory Values ALT Day 7	16.7 IU/L Standard Deviation 3.9	27.8 IU/L Standard Deviation 24.1	17.8 IU/L Standard Deviation 6.3	16.7 IU/L Standard Deviation 10.7	—
Change in Clinical Laboratory Values ALT Day 13	—	—	—	—	18.1 IU/L Standard Deviation 5.1
Change in Clinical Laboratory Values Amylase Day 3	26.5 IU/L Standard Deviation 8.0	32.2 IU/L Standard Deviation 13.7	21.8 IU/L Standard Deviation 8.7	26.8 IU/L Standard Deviation 8.0	28.0 IU/L Standard Deviation 7.9
Change in Clinical Laboratory Values Amylase Day 6	—	—	—	—	32.8 IU/L Standard Deviation 10.1
Change in Clinical Laboratory Values Amylase Day 7	25.8 IU/L Standard Deviation 7.3	30.3 IU/L Standard Deviation 13.4	22.6 IU/L Standard Deviation 10.1	26.8 IU/L Standard Deviation 10.5	—
Change in Clinical Laboratory Values Amylase Day 13	—	—	—	—	29.8 IU/L Standard Deviation 8.8
Change in Clinical Laboratory Values AST Day 3	19.0 IU/L Standard Deviation 3.6	19.7 IU/L Standard Deviation 6.0	21.2 IU/L Standard Deviation 6.4	21.8 IU/L Standard Deviation 6.1	17.8 IU/L Standard Deviation 3.7
Change in Clinical Laboratory Values AST Day 6	—	—	—	—	19.6 IU/L Standard Deviation 4.3
Change in Clinical Laboratory Values AST Day 7	19.2 IU/L Standard Deviation 3.7	26.3 IU/L Standard Deviation 11.9	23.6 IU/L Standard Deviation 10.9	22.2 IU/L Standard Deviation 6.1	—
Change in Clinical Laboratory Values AST Day 13	—	—	—	—	18.1 IU/L Standard Deviation 5.1
Change in Clinical Laboratory Values LDH Day 3	170 IU/L Standard Deviation 20	147 IU/L Standard Deviation 14	152 IU/L Standard Deviation 31	171 IU/L Standard Deviation 48	158 IU/L Standard Deviation 15
Change in Clinical Laboratory Values LDH Day 6	—	—	—	—	166 IU/L Standard Deviation 19
Change in Clinical Laboratory Values LDH Day 7	171 IU/L Standard Deviation 22	157 IU/L Standard Deviation 27	161 IU/L Standard Deviation 17	179 IU/L Standard Deviation 39	—
Change in Clinical Laboratory Values LDH Day 13	—	—	—	—	173 IU/L Standard Deviation 21
Change in Clinical Laboratory Values Lipase Day 3	26.2 IU/L Standard Deviation 4.9	42.8 IU/L Standard Deviation 31.9	23.8 IU/L Standard Deviation 10.7	33.3 IU/L Standard Deviation 10.6	28.6 IU/L Standard Deviation 8.4
Change in Clinical Laboratory Values Lipase Day 6	—	—	—	—	35.5 IU/L Standard Deviation 13.6
Change in Clinical Laboratory Values Lipase Day 7	26.8 IU/L Standard Deviation 3.9	35.8 IU/L Standard Deviation 10.5	26.6 IU/L Standard Deviation 13.6	32.0 IU/L Standard Deviation 13.3	—
Change in Clinical Laboratory Values Lipase Day 13	—	—	—	—	31.4 IU/L Standard Deviation 9.3

PRIMARY outcome

Timeframe: Day 1 for the Single Ascending Dose and Day 6 for the Multiple Single Dose, prior to 1st dose then 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post dose and Day 1 Multiple Single Dose prior to dosing then 0.5, 1, 2, and 4 hours post dose

Population: Area under the curve from 0 to 48 hours (AUC 0-48)

Area under the curve of BIO 300 Oral Powder as assessed by analyzing serum concentrations of genistein-aglycone (free genistein) at multiple timepoints

Outcome measures

Outcome measures
Measure	Single Ascending Dose Cohort 1 n=6 Participants 500 mg BIO 300 Oral Powder administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 2 n=6 Participants 1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 3 n=6 Participants 2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Single Ascending Dose Cohort 4 n=6 Participants Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 n=8 Participants Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days BIO 300 Oral Powder: Amorphous solid dispersion of genistein milled into a powder
Area Under Curve of Genistein-Aglycone in Serum	902.9 ng/mL*hr Standard Deviation 605.1	1530.9 ng/mL*hr Standard Deviation 518.2	1730.8 ng/mL*hr Standard Deviation 361.6	5836.0 ng/mL*hr Standard Deviation 3280.8	2957.3 ng/mL*hr Standard Deviation 1222.4

SECONDARY outcome

Timeframe: Day 1 for the Single Ascending Dose prior to dosing then 1, 2, 4, and 24 hours post dose and Day 1 Multiple Single Dose prior to dosing then 1, 2, and 4 hours post dose and and Day 6 prior to dosing then 4, 8, 12 and 24 hours post dose

Population: All participants had samples collected for RNA sequencing. Overall number of participants analyzed indicates the number of participants from each cohort that had samples analyzed by RNA sequencing.

The number of significantly differentially expressed genes detected in whole blood samples at various timepoints after BIO 300 Oral Powder dosing. Significant differential gene expression was defined as genes that have a mean absolute log2 fold change \>2 with an adjusted p-value of \<0.05 relative to baseline expression levels.