BIO 300 Oral Powder Safety and Pharmacokinetics

NCT04650555 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CL0106-01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Radiation Syndrome

Outcome Measures

Primary Outcomes (7)

• 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

• Area Under Curve of Genistein-Aglycone in Serum

  Area under the curve of BIO 300 Oral Powder as assessed by analyzing serum concentrations of genistein-aglycone (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 Outcomes (1)

• Number of Differentially Expressed Genes From Whole Blood Samples

  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

Study Arms (5)

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

BIO 300 Oral Powder DRUG

Amorphous solid dispersion of genistein milled into a powder

Also known as: BIO 300, Genistein

Multiple Single Dose Cohort 5; Single Ascending Dose Cohort 1; Single Ascending Dose Cohort 2; Single Ascending Dose Cohort 3; Single Ascending Dose Cohort 4

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Humanetics Corporation: lead
• United States Department of Defense: collaborator
• Joint Warfighter Medical Research Program: collaborator

Study Sites (1)

Nucleus Network, Ltd (Formally Prism Research, LLC)

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (1)

• 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.

  PMID: 36301689 RESULT

MeSH Terms

Conditions

Acute Radiation Syndrome

Interventions

Genistein

Condition Hierarchy (Ancestors)

Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Isoflavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Michael D Kaytor, PhD
• Organization: Humanetics Corporation

mkaytor@humaneticscorp.com

952-400-0405

Study Officials

• Michael D Kaytor, Ph.D.

  Humanetics Corporation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: December 2, 2020
• Study Start: December 8, 2020
• Primary Completion: July 6, 2021
• Study Completion: July 6, 2021
• Last Updated: May 3, 2024
• Results First Posted: May 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)