BIO 300 Oral Powder Safety and Pharmacokinetics

Study Overview
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Brief Summary
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Open-label, single ascending dose and multiple single dose study in healthy volunteers to evaluate the safety and pharmacokinetics of BIO 300 Oral Powder (BIO 300). The single ascending dose study consists of 4 ascending dose cohorts and the multiple single dose study consists of a single dose given daily for 6 consecutive days.

Official Title
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A Phase 1 Dose Escalation Trial Evaluating the Safety and Pharmacokinetic Profile of BIO 300 Oral Powder in Healthy Volunteers

Conditions
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Acute Radiation Syndrome

Intervention / Treatment
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* Drug: BIO 300 Oral Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult non-smokers, 18-64 years old. BMI 18-32 kg/m^2. No ingestion of prescription or over-the-counter medications (including dietary and herbal supplements) for 7 days prior to first dose of study drug and no planned use during study participation. Acetaminophen of up to 3 g/day and ibuprofen up to 1 g/day will be allowed at discretion of the Investigator. At the discretion of the Investigator, blood routine, liver and kidney functions are within the controllable range. Adequate hepatic function as evidenced by ALT, AST or LDH < 1.25X ULN and bilirubin < 1.5X ULN for the reference lab. Adequate renal function as evidenced by a serum creatinine ≤ 1.5 X ULN for the reference laboratory OR a calculated creatinine clearance of ≥ 60 mL/min by the Cockcroft-Gault Equation. Adequate hematopoietic function as evidenced by white blood cells ≥ 3x10^9 / L and platelets ≥ 100x10^9 / L. Female subjects of childbearing potential must have a negative pregnancy test within 72 hours of the start of treatment. Subjects must agree to abstain from heterosexual intercourse or use a reliable method of contraception for 7 days after their last dose. Subjects using hormonal contraception are required to utilize condom/spermicide + additional barrier method for 7 days after their last dose. Ability to read and provide written informed consent. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, dietary restrictions, and other study procedures. No clinically significant abnormalities identified by medical history, physical examination, vital signs, ECG, and clinical laboratory tests in the opinion of the Investigator. Exclusion Criteria: Any prior use of the study test article. Any clinically significant weight loss any time in prior 4 weeks at discretion of Investigator based on medical history interview. Subjects with any of the following are not eligible; Previous history of QTc prolongation resulting from known-risk medications (www.Crediblemeds.org) that required discontinuation of that medication; Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age; Presence of left bundle branch block (LBBB); QTc with Fridericia's correction (QTcF) that is unmeasurable, or ≥ 480 msec on screening ECG. The average QTcF from the screening ECG (completed in triplicate) must be < 480 msec in order for the subject to be eligible for the study. Subjects must not have had a clinically significant cardiac event such as myocardial infarction (within 6 months prior to the first dose of the study treatment); uncontrolled/symptomatic congestive heart failure (New York Heart Association (NYHA) classification of heart disease, Class III or IV, see Appendix 3) within 6 months before entry; or the presence of any other uncontrolled cardiovascular conditions [unstable hypertension at discretion of Investigator or arrhythmia, unstable angina pectoris, or severe valvular heart disease, etc.] that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. Subjects with a history of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE Grade 3) or asymptomatic sustained ventricular tachycardia are not eligible. Subjects with atrial fibrillation with well-controlled ventricular rate are eligible at the discretion of the Investigator. Psychiatric conditions, social situations or substance abuse that precludes the ability of the subject to cooperate with the requirements of the trial and protocol therapy at Investigator discretion. Inability to refrain from alcohol consumption for 48 hours prior to day 1 and for the duration of the study. Illicit drugs, including THC, must be avoided from screen through the duration of the study. Grade 2 or higher peripheral neuropathy. Positive results for Hep B surface antigen, Hep C antibody, or HIV 1/2 antibody at screening visit. Clinically significant immunodeficiency disorder in the opinion of the Investigator. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception. Women who are breastfeeding are not eligible for this study. Subjects that are vegan, vegetarian or consume a soy-rich diet. Any history of systemic infection requiring hospitalization, systemic antibiotics, or as judged clinically significant by the investigator in the 3 months prior to day 1. Any condition possibly affecting drug absorption (e.g., prior bariatric surgery, gastrectomy, intestinal resection). Participants who have undergone appendectomy or cholecystectomy are allowed so long as the surgery occurred more than 6 months prior to day 1. Treatment with another investigational drug within 30 days or 5 half-lives (whichever is longer) proceeding Day 1. Positive drug screen or alcohol test at screen and day 1 predose. Blood donation of approximately 1 pint (500 ml) or more within 60 days of day 1; plasma donations within 14 days of day 1. Subjects must agree not to donate blood or plasma for the duration of the study and for 30 days following end of study procedures. Inability to swallow powdered medication followed with water. History of sensitivity to heparin or heparin-induced thrombocytopenia. Considered by the Investigator to be unsuitable to participate in the study for any other reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose Cohort 1<br>500 mg BIO 300 Oral Powder administered as a single dose | Drug: BIO 300 Oral Powder<br>* Amorphous solid dispersion of genistein milled into a powder<br>* Other names: Genistein;|
| Experimental: Single Ascending Dose Cohort 2<br>1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose | Drug: BIO 300 Oral Powder<br>* Amorphous solid dispersion of genistein milled into a powder<br>* Other names: Genistein;|
| Experimental: Single Ascending Dose Cohort 3<br>2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose | Drug: BIO 300 Oral Powder<br>* Amorphous solid dispersion of genistein milled into a powder<br>* Other names: Genistein;|
| Experimental: Single Ascending Dose Cohort 4<br>Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3 | Drug: BIO 300 Oral Powder<br>* Amorphous solid dispersion of genistein milled into a powder<br>* Other names: Genistein;|
| Experimental: Multiple Single Dose Cohort 5<br>Highest dose or maximum tolerated dose from the Single Ascending Dose study administered as a single dose given daily for 6 consecutive days | Drug: BIO 300 Oral Powder<br>* Amorphous solid dispersion of genistein milled into a powder<br>* Other names: Genistein;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events Related to BIO 300 Oral Powder | Evaluate the safety of single and multiple dose BIO 300 Oral Powder administration | Day 1 up to 1 week for Single Ascending Dose and Day 1 up to 2 weeks for Multiple Single Dose | 
| Change in ECG QTc interval | Measurement of the average QTc interval with Fridericia's correction (completed in triplicate at each timepoint) | Day 1 up to 1 week for Single Ascending Dose and Day 1 up to 2 weeks for Multiple Single Dose | 
| Change in Clinical Laboratory Values | Monitoring of blood serum levels of albumin and total protein (all reported as g/dL) | Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose | 
| Change in Clinical Laboratory Values | Monitoring of blood serum levels of bicarbonate, chloride, potassium, and sodium (all reported as mEq/L) | Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose | 
| Change in Clinical Laboratory Values | 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) | Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose | 
| Change in Clinical Laboratory Values | Monitoring of blood serum levels of alkaline phosphatase, ALT, amylase, AST, LDH, and lipase (all reported as IU/L) | Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose | 
| BIO 300 Oral Powder Pharmacokinetics | Pharmacokinetics as assessed by analyzing serum concentrations of free genistein at multiple timepoints | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BIO 300 Oral Powder Pharmacodynamics - gene expression | Pharmacodynamic biomarkers characterized by analyzing RNA from whole blood samples to identify differentially expressed genes at multiple timepoints | Day 1 for the Single Ascending Dose and Day 6 for the Multiple Single 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 |