BIO 300 Oral Powder Safety and Pharmacokinetics | NCT04650555

NCT04650555

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Name	Class
United States Department of Defense	FED
Joint Warfighter Medical Research Program	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Single Ascending Dose Cohort 1	Experimental	500 mg BIO 300 Oral Powder administered as a single dose	Drug: BIO 300 Oral Powder
Single Ascending Dose Cohort 2	Experimental	1000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose	Drug: BIO 300 Oral Powder
Single Ascending Dose Cohort 3	Experimental	2000 mg BIO 300 Oral Powder, if dose escalation criteria met, administered as a single dose	Drug: BIO 300 Oral Powder
Single Ascending Dose Cohort 4	Experimental	Single dose to be determined based on the safety and pharmacokinetic profiles in cohorts 1-3	Drug: BIO 300 Oral Powder
Multiple Single Dose Cohort 5	Experimental	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
BIO 300 Oral Powder	Drug	Amorphous solid dispersion of genistein milled into a powder	Multiple Single Dose Cohort 5 Single Ascending Dose Cohort 1 Single Ascending Dose Cohort 2

Outcomes Module

Primary Outcomes

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 after the last dose for Single Ascending Dose and Multiple Single Dose Cohorts
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

Secondary Outcomes

Measure	Description	Time Frame
Number of Differentially Expressed Genes From Whole Blood Samples	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.	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

Eligibility Module

Eligibility Criteria

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.
1. Adequate hepatic function as evidenced by ALT, AST or LDH < 1.25X ULN and bilirubin < 1.5X ULN for the reference lab.
2. 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.
3. 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;
1. Previous history of QTc prolongation resulting from "known-risk" medications (www.Crediblemeds.org) that required discontinuation of that medication;
2. Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age;
3. Presence of left bundle branch block (LBBB);
4. 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.

Contacts/Locations Module

Name	Affiliation	Role
Michael D Kaytor, Ph.D.	Humanetics Corporation	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Nucleus Network, Ltd (Formally Prism Research, LLC)		Saint Paul	Minnesota	55114	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36301689	Result	Serebrenik AA, Verduyn CW, Kaytor MD. Safety, Pharmacokinetics, and Biomarkers of an Amorphous Solid Dispersion of Genistein, a Radioprotectant, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2023 Feb;12(2):190-201. doi: 10.1002/cpdd.1188. Epub 2022 Oct 27.

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	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
FG001	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
FG002	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
FG003	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
FG004	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

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0006 subjects FG0016 subjects FG0026 subjects FG0036 subjects FG00410 subjects
COMPLETED		FG0006 subjects FG0016 subjects FG0025 subjects FG0036 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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
BG001	Single Ascending Dose Cohort 2

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Adverse Events Related to BIO 300 Oral Powder

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

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

Posted

Number

Number of Adverse Events

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

Number of Adverse Events

ID	Title	Description
OG000	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
OG001	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

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Palpitations	Cardiac disorders		Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Michael D Kaytor, PhD	Humanetics Corporation	952-400-0405		mkaytor@humaneticscorp.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 7, 2021	Nov 23, 2022	Prot_SAP_000.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D054508	Acute Radiation Syndrome

ID	Term
D011832	Radiation Injuries
D014947	Wounds and Injuries

Intervention Browse Module

ID	Term
D019833	Genistein

ID	Term
D007529	Isoflavones
D005419	Flavonoids
D002867	Chromones
D001578	Benzopyrans
D011714

Masking Info

Single Ascending Dose Cohort 3

Single Ascending Dose Cohort 4

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

EG0000 events0 affected6 at risk

EG0010 events0 affected6 at risk

EG0020 events0 affected6 at risk

EG0030 events0 affected6 at risk

EG0041 events1 affected10 at risk

OG0042957.3± 1222.4