Acute Radiation Syndrome
Conditions
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.
Interventions
DRUGBIO 300 Oral Powder
Amorphous solid dispersion of genistein milled into a powder
Sponsors
United States Department of Defense
Joint Warfighter Medical Research Program
Humanetics Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adult non-smokers, 18-64 years old. 2. BMI 18-32 kg/m\^2. 3. 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. 4. 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. 5. Female subjects of childbearing potential must have a negative pregnancy test within 72 hours of the start of treatment. 6. 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. 7. Ability to read and provide written informed consent. 8. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, dietary restrictions, and other study procedures. 9. 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
1. Any prior use of the study test article. 2. Any clinically significant weight loss any time in prior 4 weeks at discretion of Investigator based on medical history interview. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. Grade 2 or higher peripheral neuropathy. 9. Positive results for Hep B surface antigen, Hep C antibody, or HIV 1/2 antibody at screening visit. 10. Clinically significant immunodeficiency disorder in the opinion of the Investigator. 11. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception. 12. Women who are breastfeeding are not eligible for this study. 13. Subjects that are vegan, vegetarian or consume a soy-rich diet. 14. 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. 15. 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. 16. Treatment with another investigational drug within 30 days or 5 half-lives (whichever is longer) proceeding Day 1. 17. Positive drug screen or alcohol test at screen and day 1 predose. 18. 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. 19. Inability to swallow powdered medication followed with water. 20. History of sensitivity to heparin or heparin-induced thrombocytopenia. 21. Considered by the Investigator to be unsuitable to participate in the study for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Related to BIO 300 Oral Powder | Day 1 up to 1 week for Single Ascending Dose and Day 1 up to 2 weeks for Multiple Single Dose | Evaluate the safety of single and multiple dose BIO 300 Oral Powder administration |
| Change in ECG QTc Interval | 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) |
| Change in Clinical Laboratory Values | Day 3 and 7 for Single Ascending Dose and Day 3, 6 and 13 for Multiple Single Dose | Monitoring of blood serum levels of albumin and total protein (all reported as g/dL) |
| Area Under Curve of Genistein-Aglycone in Serum | 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 | Area under the curve of BIO 300 Oral Powder as assessed by analyzing serum concentrations of genistein-aglycone (free genistein) at multiple timepoints |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 6 |
| 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 | 6 |
| 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 | 6 |
| 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 | 6 |
| 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 | 10 |
| Total | 34 |
Baseline characteristics
| Characteristic | Single Ascending Dose Cohort 1 | Total | Multiple Single Dose Cohort 5 | Single Ascending Dose Cohort 4 | Single Ascending Dose Cohort 3 | Single Ascending Dose Cohort 2 |
|---|---|---|---|---|---|---|
| Age, Continuous | 55 years | 45 years | 46 years | 48 years | 40 years | 37 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 33 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 29 Participants | 8 Participants | 5 Participants | 5 Participants | 6 Participants |
| Region of Enrollment United States | 6 participants | 34 participants | 10 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 4 Participants | 18 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 16 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 |
| other Total, other adverse events | 0 / 6 | 4 / 6 | 2 / 6 | 5 / 6 | 8 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 |
Outcome results
Primary
Adverse Events Related to BIO 300 Oral Powder
Evaluate the safety of single and multiple dose BIO 300 Oral Powder administration
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Ascending Dose Cohort 2 | Adverse Events Related to BIO 300 Oral Powder | Dose Limiting Toxicities | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 2 | Adverse Events Related to BIO 300 Oral Powder | Unlikely Treatment-Related Adverse Events | 1 Number of Adverse Events |
| Single Ascending Dose Cohort 2 | Adverse Events Related to BIO 300 Oral Powder | Possibly Treatment-Related Adverse Events | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 2 | Adverse Events Related to BIO 300 Oral Powder | Probably Treatment-Related Adverse Events | 4 Number of Adverse Events |
| Single Ascending Dose Cohort 2 | Adverse Events Related to BIO 300 Oral Powder | Definitely Treatment-Related Adverse Events | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 2 | Adverse Events Related to BIO 300 Oral Powder | Unrelated Adverse Event | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 3 | Adverse Events Related to BIO 300 Oral Powder | Unrelated Adverse Event | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 3 | Adverse Events Related to BIO 300 Oral Powder | Probably Treatment-Related Adverse Events | 4 Number of Adverse Events |
| Single Ascending Dose Cohort 3 | Adverse Events Related to BIO 300 Oral Powder | Dose Limiting Toxicities | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 3 | Adverse Events Related to BIO 300 Oral Powder | Possibly Treatment-Related Adverse Events | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 3 | Adverse Events Related to BIO 300 Oral Powder | Unlikely Treatment-Related Adverse Events | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 3 | Adverse Events Related to BIO 300 Oral Powder | Definitely Treatment-Related Adverse Events | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 4 | Adverse Events Related to BIO 300 Oral Powder | Unlikely Treatment-Related Adverse Events | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 4 | Adverse Events Related to BIO 300 Oral Powder | Possibly Treatment-Related Adverse Events | 3 Number of Adverse Events |
| Single Ascending Dose Cohort 4 | Adverse Events Related to BIO 300 Oral Powder | Probably Treatment-Related Adverse Events | 0 Number of Adverse Events |
| Single Ascending Dose Cohort 4 | Adverse Events Related to BIO 300 Oral Powder | Unrelated Adverse Event | 1 Number of Adverse Events |
| Single Ascending Dose Cohort 4 | Adverse Events Related to BIO 300 Oral Powder | Definitely Treatment-Related Adverse Events | 2 Number of Adverse Events |
| Single Ascending Dose Cohort 4 | Adverse Events Related to BIO 300 Oral Powder | Dose Limiting Toxicities | 0 Number of Adverse Events |
| Multiple Single Dose Cohort 5 | Adverse Events Related to BIO 300 Oral Powder | Definitely Treatment-Related Adverse Events | 1 Number of Adverse Events |
| Multiple Single Dose Cohort 5 | Adverse Events Related to BIO 300 Oral Powder | Unrelated Adverse Event | 1 Number of Adverse Events |
| Multiple Single Dose Cohort 5 | Adverse Events Related to BIO 300 Oral Powder | Unlikely Treatment-Related Adverse Events | 2 Number of Adverse Events |
| Multiple Single Dose Cohort 5 | Adverse Events Related to BIO 300 Oral Powder | Probably Treatment-Related Adverse Events | 15 Number of Adverse Events |
| Multiple Single Dose Cohort 5 | Adverse Events Related to BIO 300 Oral Powder | Dose Limiting Toxicities | 0 Number of Adverse Events |
| Multiple Single Dose Cohort 5 | Adverse Events Related to BIO 300 Oral Powder | Possibly Treatment-Related Adverse Events | 7 Number of Adverse Events |
Primary
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
Time frame: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Ascending Dose Cohort 1 | Area Under Curve of Genistein-Aglycone in Serum | 902.9 ng/mL*hr | Standard Deviation 605.1 |
| Single Ascending Dose Cohort 2 | Area Under Curve of Genistein-Aglycone in Serum | 1530.9 ng/mL*hr | Standard Deviation 518.2 |
| Single Ascending Dose Cohort 3 | Area Under Curve of Genistein-Aglycone in Serum | 1730.8 ng/mL*hr | Standard Deviation 361.6 |
| Single Ascending Dose Cohort 4 | Area Under Curve of Genistein-Aglycone in Serum | 5836.0 ng/mL*hr | Standard Deviation 3280.8 |
| Multiple Single Dose Cohort 5 | Area Under Curve of Genistein-Aglycone in Serum | 2957.3 ng/mL*hr | Standard Deviation 1222.4 |
Primary
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)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Calcium Day 3 | 9.73 mg/dL | Standard Deviation 0.37 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Uric Acid Day 3 | 5.25 mg/dL | Standard Deviation 1.08 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Creatinine Day 7 | 0.873 mg/dL | Standard Deviation 0.147 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | BUN Day 7 | 16.67 mg/dL | Standard Deviation 4.23 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Creatinine Day 3 | 0.905 mg/dL | Standard Deviation 0.182 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | HDL Day 7 | 52 mg/dL | Standard Deviation 9 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Triglycerides Day 3 | 80.2 mg/dL | Standard Deviation 43.3 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Uric Acid Day 7 | 5.13 mg/dL | Standard Deviation 1.09 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | HDL Day 3 | 52 mg/dL | Standard Deviation 11 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Phosphorous Day 7 | 3.62 mg/dL | Standard Deviation 0.53 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | BUN Day 3 | 18.00 mg/dL | Standard Deviation 3.46 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Total Bilirubin Day 3 | 0.467 mg/dL | Standard Deviation 0.308 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Magnesium Day 3 | 2.10 mg/dL | Standard Deviation 0.11 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Glucose Day 3 | 95.2 mg/dL | Standard Deviation 8 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Direct Bilirubin Day 3 | 0.200 mg/dL | Standard Deviation 0 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Calcium Day 7 | 9.47 mg/dL | Standard Deviation 0.14 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Cholesterol Day 7 | 195 mg/dL | Standard Deviation 34 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Triglycerides Day 7 | 71.3 mg/dL | Standard Deviation 22.1 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Total Bilirubin Day 7 | 0.483 mg/dL | Standard Deviation 0.331 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Direct Bilirubin Day 7 | 0.200 mg/dL | Standard Deviation 0 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Cholesterol Day 3 | 200 mg/dL | Standard Deviation 43 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Magnesium Day 7 | 2.02 mg/dL | Standard Deviation 0.12 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Phosphorous Day 3 | 3.58 mg/dL | Standard Deviation 0.37 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Glucose Day 7 | 101.5 mg/dL | Standard Deviation 10 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | HDL Day 7 | 54 mg/dL | Standard Deviation 16 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Cholesterol Day 7 | 180 mg/dL | Standard Deviation 33 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Phosphorous Day 3 | 3.62 mg/dL | Standard Deviation 0.45 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | HDL Day 3 | 55 mg/dL | Standard Deviation 15 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Total Bilirubin Day 3 | 0.417 mg/dL | Standard Deviation 0.117 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Creatinine Day 3 | 0.943 mg/dL | Standard Deviation 0.154 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Triglycerides Day 3 | 104.2 mg/dL | Standard Deviation 91 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Creatinine Day 7 | 1.028 mg/dL | Standard Deviation 0.15 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Magnesium Day 7 | 2.12 mg/dL | Standard Deviation 0.1 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Direct Bilirubin Day 7 | 0.200 mg/dL | Standard Deviation 0 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Magnesium Day 3 | 2.05 mg/dL | Standard Deviation 0.14 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Glucose Day 7 | 92.3 mg/dL | Standard Deviation 2.7 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Triglycerides Day 7 | 117.3 mg/dL | Standard Deviation 107 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Uric Acid Day 3 | 4.62 mg/dL | Standard Deviation 1.26 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | BUN Day 3 | 13.33 mg/dL | Standard Deviation 2.94 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Calcium Day 3 | 9.38 mg/dL | Standard Deviation 0.32 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | BUN Day 7 | 14.50 mg/dL | Standard Deviation 2.88 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Uric Acid Day 7 | 5.30 mg/dL | Standard Deviation 1.89 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Glucose Day 3 | 89.7 mg/dL | Standard Deviation 7.3 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Calcium Day 7 | 9.37 mg/dL | Standard Deviation 0.26 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Phosphorous Day 7 | 3.68 mg/dL | Standard Deviation 0.42 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Direct Bilirubin Day 3 | 0.200 mg/dL | Standard Deviation 0 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Cholesterol Day 3 | 181 mg/dL | Standard Deviation 23 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Total Bilirubin Day 7 | 0.583 mg/dL | Standard Deviation 0.417 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Direct Bilirubin Day 3 | 0.200 mg/dL | Standard Deviation 0 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Total Bilirubin Day 7 | 0.340 mg/dL | Standard Deviation 0.167 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Phosphorous Day 3 | 3.75 mg/dL | Standard Deviation 0.41 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Phosphorous Day 7 | 3.70 mg/dL | Standard Deviation 0.49 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | BUN Day 7 | 14.20 mg/dL | Standard Deviation 5.85 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Triglycerides Day 3 | 80.5 mg/dL | Standard Deviation 37.5 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Triglycerides Day 7 | 79.2 mg/dL | Standard Deviation 44.5 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Uric Acid Day 3 | 4.48 mg/dL | Standard Deviation 1.16 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Calcium Day 3 | 9.27 mg/dL | Standard Deviation 0.23 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Uric Acid Day 7 | 4.10 mg/dL | Standard Deviation 0.73 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Calcium Day 7 | 9.18 mg/dL | Standard Deviation 0.37 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Cholesterol Day 3 | 158 mg/dL | Standard Deviation 19 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Magnesium Day 7 | 2.06 mg/dL | Standard Deviation 0.11 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Cholesterol Day 7 | 173 mg/dL | Standard Deviation 32 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Creatinine Day 3 | 0.883 mg/dL | Standard Deviation 0.18 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Total Bilirubin Day 3 | 0.333 mg/dL | Standard Deviation 0.137 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Creatinine Day 7 | 0.954 mg/dL | Standard Deviation 0.212 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | HDL Day 3 | 52 mg/dL | Standard Deviation 10 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Direct Bilirubin Day 7 | 0.200 mg/dL | Standard Deviation 0 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | HDL Day 7 | 56 mg/dL | Standard Deviation 9 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Glucose Day 3 | 90.7 mg/dL | Standard Deviation 6.5 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Glucose Day 7 | 97.0 mg/dL | Standard Deviation 12.1 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | BUN Day 3 | 14.83 mg/dL | Standard Deviation 4.62 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Magnesium Day 3 | 2.07 mg/dL | Standard Deviation 0.12 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Direct Bilirubin Day 3 | 0.200 mg/dL | Standard Deviation 0 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Cholesterol Day 3 | 210 mg/dL | Standard Deviation 44 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Magnesium Day 3 | 1.90 mg/dL | Standard Deviation 0.17 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | HDL Day 7 | 71 mg/dL | Standard Deviation 23 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Calcium Day 7 | 9.50 mg/dL | Standard Deviation 0.32 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Total Bilirubin Day 3 | 0.650 mg/dL | Standard Deviation 0.501 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Calcium Day 3 | 9.72 mg/dL | Standard Deviation 0.33 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | BUN Day 3 | 13.50 mg/dL | Standard Deviation 4.51 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Glucose Day 3 | 90.2 mg/dL | Standard Deviation 8.8 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Uric Acid Day 7 | 5.08 mg/dL | Standard Deviation 1.24 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Uric Acid Day 3 | 5.07 mg/dL | Standard Deviation 1.38 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Triglycerides Day 7 | 80.5 mg/dL | Standard Deviation 39.7 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Total Bilirubin Day 7 | 0.400 mg/dL | Standard Deviation 0.141 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Phosphorous Day 7 | 3.68 mg/dL | Standard Deviation 0.62 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Glucose Day 7 | 105.8 mg/dL | Standard Deviation 40.8 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Phosphorous Day 3 | 3.52 mg/dL | Standard Deviation 0.34 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | BUN Day 7 | 13.83 mg/dL | Standard Deviation 4.26 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Creatinine Day 7 | 0.980 mg/dL | Standard Deviation 0.131 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Creatinine Day 3 | 0.900 mg/dL | Standard Deviation 0.127 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Cholesterol Day 7 | 213 mg/dL | Standard Deviation 49 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Triglycerides Day 3 | 85.5 mg/dL | Standard Deviation 30.6 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | HDL Day 3 | 69 mg/dL | Standard Deviation 21 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Magnesium Day 7 | 1.98 mg/dL | Standard Deviation 0.12 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Direct Bilirubin Day 7 | 0.200 mg/dL | Standard Deviation 0 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Uric Acid Day 13 | 5.20 mg/dL | Standard Deviation 1.6 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Total Bilirubin Day 3 | 0.613 mg/dL | Standard Deviation 0.394 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Total Bilirubin Day 6 | 0.500 mg/dL | Standard Deviation 0.185 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Total Bilirubin Day 13 | 0.563 mg/dL | Standard Deviation 0.307 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Direct Bilirubin Day 3 | 0.200 mg/dL | Standard Deviation 0 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Direct Bilirubin Day 6 | 0.200 mg/dL | Standard Deviation 0 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Direct Bilirubin Day 13 | 0.200 mg/dL | Standard Deviation 0 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | BUN Day 3 | 11.88 mg/dL | Standard Deviation 3.09 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | BUN Day 6 | 12.00 mg/dL | Standard Deviation 2.83 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | BUN Day 13 | 11.63 mg/dL | Standard Deviation 3.82 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Calcium Day 3 | 9.25 mg/dL | Standard Deviation 0.34 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Calcium Day 6 | 9.60 mg/dL | Standard Deviation 0.19 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Calcium Day 13 | 9.36 mg/dL | Standard Deviation 0.3 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Cholesterol Day 3 | 178 mg/dL | Standard Deviation 23 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Cholesterol Day 6 | 193 mg/dL | Standard Deviation 22 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Cholesterol Day 13 | 177 mg/dL | Standard Deviation 26 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Creatinine Day 3 | 0.944 mg/dL | Standard Deviation 0.116 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Creatinine Day 6 | 1.030 mg/dL | Standard Deviation 0.099 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Creatinine Day 13 | 1.043 mg/dL | Standard Deviation 0.094 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | HDL Day 3 | 49 mg/dL | Standard Deviation 14 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | HDL Day 6 | 55 mg/dL | Standard Deviation 15 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | HDL Day 13 | 52 mg/dL | Standard Deviation 17 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Glucose Day 3 | 96.3 mg/dL | Standard Deviation 5.8 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Glucose Day 6 | 93.6 mg/dL | Standard Deviation 5.2 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Glucose Day 13 | 93.4 mg/dL | Standard Deviation 4.7 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Magnesium Day 3 | 1.98 mg/dL | Standard Deviation 0.1 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Magnesium Day 6 | 2.05 mg/dL | Standard Deviation 0.17 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Magnesium Day 13 | 2.06 mg/dL | Standard Deviation 0.09 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Phosphorous Day 3 | 3.14 mg/dL | Standard Deviation 0.36 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Phosphorous Day 6 | 3.49 mg/dL | Standard Deviation 0.34 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Phosphorous Day 13 | 0.39 mg/dL | Standard Deviation 0.54 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Triglycerides Day 3 | 101.9 mg/dL | Standard Deviation 38.8 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Triglycerides Day 6 | 98.6 mg/dL | Standard Deviation 23.3 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Triglycerides Day 13 | 89.8 mg/dL | Standard Deviation 20.6 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Uric Acid Day 3 | 5.20 mg/dL | Standard Deviation 1.5 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Uric Acid Day 6 | 5.21 mg/dL | Standard Deviation 1.55 |
Primary
Change in Clinical Laboratory Values
Monitoring of blood serum levels of alkaline phosphatase, ALT, amylase, AST, LDH, and lipase (all reported as IU/L)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | ALP Day 7 | 69.5 IU/L | Standard Deviation 14.7 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Amylase Day 7 | 25.8 IU/L | Standard Deviation 7.3 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | LDH Day 7 | 171 IU/L | Standard Deviation 22 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | ALP Day 3 | 74.2 IU/L | Standard Deviation 18.1 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | LDH Day 3 | 170 IU/L | Standard Deviation 20 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | ALT Day 7 | 16.7 IU/L | Standard Deviation 3.9 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Lipase Day 3 | 26.2 IU/L | Standard Deviation 4.9 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | AST Day 3 | 19.0 IU/L | Standard Deviation 3.6 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | ALT Day 3 | 18.2 IU/L | Standard Deviation 5.7 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | AST Day 7 | 19.2 IU/L | Standard Deviation 3.7 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Amylase Day 3 | 26.5 IU/L | Standard Deviation 8 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Lipase Day 7 | 26.8 IU/L | Standard Deviation 3.9 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Amylase Day 3 | 32.2 IU/L | Standard Deviation 13.7 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | AST Day 3 | 19.7 IU/L | Standard Deviation 6 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Amylase Day 7 | 30.3 IU/L | Standard Deviation 13.4 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Lipase Day 3 | 42.8 IU/L | Standard Deviation 31.9 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | ALP Day 7 | 69.0 IU/L | Standard Deviation 17.3 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | LDH Day 7 | 157 IU/L | Standard Deviation 27 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | ALT Day 3 | 21.2 IU/L | Standard Deviation 18.6 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | ALP Day 3 | 66.7 IU/L | Standard Deviation 13.9 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | LDH Day 3 | 147 IU/L | Standard Deviation 14 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | ALT Day 7 | 27.8 IU/L | Standard Deviation 24.1 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Lipase Day 7 | 35.8 IU/L | Standard Deviation 10.5 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | AST Day 7 | 26.3 IU/L | Standard Deviation 11.9 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | ALP Day 7 | 68.0 IU/L | Standard Deviation 21.1 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | ALP Day 3 | 64.2 IU/L | Standard Deviation 18.8 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | ALT Day 3 | 15.2 IU/L | Standard Deviation 3.2 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | ALT Day 7 | 17.8 IU/L | Standard Deviation 6.3 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Amylase Day 3 | 21.8 IU/L | Standard Deviation 8.7 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Amylase Day 7 | 22.6 IU/L | Standard Deviation 10.1 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | AST Day 3 | 21.2 IU/L | Standard Deviation 6.4 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | AST Day 7 | 23.6 IU/L | Standard Deviation 10.9 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | LDH Day 3 | 152 IU/L | Standard Deviation 31 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | LDH Day 7 | 161 IU/L | Standard Deviation 17 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Lipase Day 3 | 23.8 IU/L | Standard Deviation 10.7 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Lipase Day 7 | 26.6 IU/L | Standard Deviation 13.6 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | AST Day 7 | 22.2 IU/L | Standard Deviation 6.1 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | ALP Day 7 | 52.5 IU/L | Standard Deviation 29.7 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | ALT Day 7 | 16.7 IU/L | Standard Deviation 10.7 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Lipase Day 7 | 32.0 IU/L | Standard Deviation 13.3 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Lipase Day 3 | 33.3 IU/L | Standard Deviation 10.6 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | ALT Day 3 | 16.2 IU/L | Standard Deviation 9.5 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | ALP Day 3 | 62.8 IU/L | Standard Deviation 21.4 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Amylase Day 7 | 26.8 IU/L | Standard Deviation 10.5 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | LDH Day 3 | 171 IU/L | Standard Deviation 48 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | LDH Day 7 | 179 IU/L | Standard Deviation 39 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Amylase Day 3 | 26.8 IU/L | Standard Deviation 8 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | AST Day 3 | 21.8 IU/L | Standard Deviation 6.1 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | LDH Day 13 | 173 IU/L | Standard Deviation 21 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | ALP Day 6 | 60.3 IU/L | Standard Deviation 16.2 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Amylase Day 6 | 32.8 IU/L | Standard Deviation 10.1 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Lipase Day 3 | 28.6 IU/L | Standard Deviation 8.4 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Amylase Day 13 | 29.8 IU/L | Standard Deviation 8.8 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Amylase Day 3 | 28.0 IU/L | Standard Deviation 7.9 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Lipase Day 6 | 35.5 IU/L | Standard Deviation 13.6 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | AST Day 3 | 17.8 IU/L | Standard Deviation 3.7 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | AST Day 6 | 19.6 IU/L | Standard Deviation 4.3 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | ALT Day 13 | 18.1 IU/L | Standard Deviation 5.1 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | ALP Day 3 | 59.5 IU/L | Standard Deviation 15.5 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | AST Day 13 | 18.1 IU/L | Standard Deviation 5.1 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | ALT Day 6 | 18.4 IU/L | Standard Deviation 4.1 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | ALT Day 3 | 17.6 IU/L | Standard Deviation 5.5 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | LDH Day 3 | 158 IU/L | Standard Deviation 15 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | LDH Day 6 | 166 IU/L | Standard Deviation 19 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | ALP Day 13 | 59.4 IU/L | Standard Deviation 18.6 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Lipase Day 13 | 31.4 IU/L | Standard Deviation 9.3 |
Primary
Change in Clinical Laboratory Values
Monitoring of blood serum levels of bicarbonate, chloride, potassium, and sodium (all reported as mEq/L)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Potassium Day 7 | 4.217 mEq/L | Standard Deviation 0.279 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Chloride Day 7 | 104.3 mEq/L | Standard Deviation 1.366 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Bicarbonate Day 3 | 26.833 mEq/L | Standard Deviation 1.722 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Sodium Day 3 | 140.7 mEq/L | Standard Deviation 1.966 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Chloride Day 3 | 104.5 mEq/L | Standard Deviation 2.429 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Sodium Day 7 | 140.0 mEq/L | Standard Deviation 1.265 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Potassium Day 3 | 4.417 mEq/L | Standard Deviation 0.271 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Bicarbonate Day 7 | 26.500 mEq/L | Standard Deviation 1.871 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Potassium Day 3 | 4.500 mEq/L | Standard Deviation 0.141 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Bicarbonate Day 3 | 26.167 mEq/L | Standard Deviation 0.753 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Potassium Day 7 | 4.483 mEq/L | Standard Deviation 0.306 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Bicarbonate Day 7 | 27.500 mEq/L | Standard Deviation 1.761 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Sodium Day 7 | 139.2 mEq/L | Standard Deviation 1.472 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Chloride Day 3 | 104.0 mEq/L | Standard Deviation 1.549 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Chloride Day 7 | 104.5 mEq/L | Standard Deviation 1.761 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Sodium Day 3 | 139.5 mEq/L | Standard Deviation 1.225 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Bicarbonate Day 7 | 29.000 mEq/L | Standard Deviation 0.707 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Sodium Day 3 | 140.7 mEq/L | Standard Deviation 0.816 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Sodium Day 7 | 139.2 mEq/L | Standard Deviation 1.304 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Potassium Day 7 | 4.580 mEq/L | Standard Deviation 0.46 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Chloride Day 7 | 104.2 mEq/L | Standard Deviation 1.095 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Potassium Day 3 | 4.617 mEq/L | Standard Deviation 0.306 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Chloride Day 3 | 104.7 mEq/L | Standard Deviation 0.816 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Bicarbonate Day 3 | 27.167 mEq/L | Standard Deviation 2.401 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Potassium Day 7 | 4.233 mEq/L | Standard Deviation 0.151 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Sodium Day 3 | 140.2 mEq/L | Standard Deviation 1.835 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Bicarbonate Day 7 | 28.667 mEq/L | Standard Deviation 1.751 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Sodium Day 7 | 142.3 mEq/L | Standard Deviation 2.066 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Chloride Day 3 | 103.5 mEq/L | Standard Deviation 0.837 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Bicarbonate Day 3 | 27.500 mEq/L | Standard Deviation 1.049 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Chloride Day 7 | 104.8 mEq/L | Standard Deviation 2.317 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Potassium Day 3 | 4.400 mEq/L | Standard Deviation 0.303 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Sodium Day 13 | 140.1 mEq/L | Standard Deviation 1.727 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Bicarbonate Day 3 | 23.875 mEq/L | Standard Deviation 2.85 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Bicarbonate Day 6 | 23.750 mEq/L | Standard Deviation 1.165 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Bicarbonate Day 13 | 23.125 mEq/L | Standard Deviation 1.246 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Chloride Day 3 | 105.5 mEq/L | Standard Deviation 1.927 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Chloride Day 6 | 103.8 mEq/L | Standard Deviation 2.252 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Potassium Day 3 | 4.288 mEq/L | Standard Deviation 0.318 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Potassium Day 6 | 4.413 mEq/L | Standard Deviation 0.336 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Potassium Day 13 | 4.288 mEq/L | Standard Deviation 0.155 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Sodium Day 3 | 140.0 mEq/L | Standard Deviation 1.414 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Sodium Day 6 | 139.5 mEq/L | Standard Deviation 1.414 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Chloride Day 13 | 105.1 mEq/L | Standard Deviation 0.835 |
Primary
Change in Clinical Laboratory Values
Monitoring of blood serum levels of albumin and total protein (all reported as g/dL)
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Albumin Day 3 | 4.483 g/dL | Standard Deviation 0.204 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Albumin Day 7 | 4.233 g/dL | Standard Deviation 0.216 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Total Protein Day 3 | 6.667 g/dL | Standard Deviation 0.344 |
| Single Ascending Dose Cohort 1 | Change in Clinical Laboratory Values | Total Protein Day 7 | 6.417 g/dL | Standard Deviation 0.331 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Albumin Day 7 | 4.283 g/dL | Standard Deviation 0.279 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Total Protein Day 7 | 6.850 g/dL | Standard Deviation 0.619 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Albumin Day 3 | 4.433 g/dL | Standard Deviation 0.393 |
| Single Ascending Dose Cohort 2 | Change in Clinical Laboratory Values | Total Protein Day 3 | 6.833 g/dL | Standard Deviation 0.638 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Total Protein Day 7 | 6.520 g/dL | Standard Deviation 0.438 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Total Protein Day 3 | 6.500 g/dL | Standard Deviation 0.369 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Albumin Day 7 | 4.440 g/dL | Standard Deviation 0.241 |
| Single Ascending Dose Cohort 3 | Change in Clinical Laboratory Values | Albumin Day 3 | 4.333 g/dL | Standard Deviation 0.367 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Albumin Day 3 | 4.550 g/dL | Standard Deviation 0.187 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Albumin Day 7 | 4.517 g/dL | Standard Deviation 0.117 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Total Protein Day 7 | 6.717 g/dL | Standard Deviation 0.454 |
| Single Ascending Dose Cohort 4 | Change in Clinical Laboratory Values | Total Protein Day 3 | 6.650 g/dL | Standard Deviation 0.547 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Total Protein Day 6 | 6.788 g/dL | Standard Deviation 0.348 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Total Protein Day 13 | 6.550 g/dL | Standard Deviation 0.518 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Total Protein Day 3 | 6.363 g/dL | Standard Deviation 0.444 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Albumin Day 13 | 4.475 g/dL | Standard Deviation 0.306 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Albumin Day 6 | 4.475 g/dL | Standard Deviation 0.249 |
| Multiple Single Dose Cohort 5 | Change in Clinical Laboratory Values | Albumin Day 3 | 4.225 g/dL | Standard Deviation 0.349 |
Primary
Change in ECG QTc Interval
Measurement of the average QTc interval with Fridericia's correction (completed in triplicate at each timepoint)
Time frame: Day 1 up to 1 week after the last dose for Single Ascending Dose and Multiple Single Dose Cohorts
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Ascending Dose Cohort 1 | Change in ECG QTc Interval | Screening | 407 milliseconds | Standard Deviation 9.3 |
| Single Ascending Dose Cohort 1 | Change in ECG QTc Interval | 4 Hours Post First Dose | 412 milliseconds | Standard Deviation 9.6 |
| Single Ascending Dose Cohort 1 | Change in ECG QTc Interval | 24 Hours Post First Dose | 407 milliseconds | Standard Deviation 11.3 |
| Single Ascending Dose Cohort 1 | Change in ECG QTc Interval | 1 Week Post Last Dose | 408 milliseconds | Standard Deviation 12.4 |
| Single Ascending Dose Cohort 2 | Change in ECG QTc Interval | Screening | 402 milliseconds | Standard Deviation 19.3 |
| Single Ascending Dose Cohort 2 | Change in ECG QTc Interval | 1 Week Post Last Dose | 401 milliseconds | Standard Deviation 18.3 |
| Single Ascending Dose Cohort 2 | Change in ECG QTc Interval | 4 Hours Post First Dose | 407 milliseconds | Standard Deviation 16.5 |
| Single Ascending Dose Cohort 2 | Change in ECG QTc Interval | 24 Hours Post First Dose | 400 milliseconds | Standard Deviation 11.2 |
| Single Ascending Dose Cohort 3 | Change in ECG QTc Interval | 1 Week Post Last Dose | 416 milliseconds | Standard Deviation 36.3 |
| Single Ascending Dose Cohort 3 | Change in ECG QTc Interval | 4 Hours Post First Dose | 419 milliseconds | Standard Deviation 27.8 |
| Single Ascending Dose Cohort 3 | Change in ECG QTc Interval | 24 Hours Post First Dose | 402 milliseconds | Standard Deviation 26.7 |
| Single Ascending Dose Cohort 3 | Change in ECG QTc Interval | Screening | 416 milliseconds | Standard Deviation 21.8 |
| Single Ascending Dose Cohort 4 | Change in ECG QTc Interval | Screening | 415 milliseconds | Standard Deviation 18.7 |
| Single Ascending Dose Cohort 4 | Change in ECG QTc Interval | 4 Hours Post First Dose | 420 milliseconds | Standard Deviation 16.3 |
| Single Ascending Dose Cohort 4 | Change in ECG QTc Interval | 1 Week Post Last Dose | 414 milliseconds | Standard Deviation 12.6 |
| Single Ascending Dose Cohort 4 | Change in ECG QTc Interval | 24 Hours Post First Dose | 404 milliseconds | Standard Deviation 41.7 |
| Multiple Single Dose Cohort 5 | Change in ECG QTc Interval | 1 Week Post Last Dose | 415 milliseconds | Standard Deviation 9 |
| Multiple Single Dose Cohort 5 | Change in ECG QTc Interval | 24 Hours Post First Dose | 413 milliseconds | Standard Deviation 9.9 |
| Multiple Single Dose Cohort 5 | Change in ECG QTc Interval | 4 Hours Post First Dose | 417 milliseconds | Standard Deviation 7.4 |
| Multiple Single Dose Cohort 5 | Change in ECG QTc Interval | Screening | 413 milliseconds | Standard Deviation 13.3 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 1 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 2 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 4 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 24 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 4 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 8 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 12 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 1 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 24 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 8 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 4 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 2 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 24 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 12 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 24 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 4 hr post-dose | 1 Differentially expressed genes |
| Single Ascending Dose Cohort 3 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 1 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 12 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 4 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 24 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 4 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 8 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 24 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 1 hr post-dose | 0 Differentially expressed genes |
| Single Ascending Dose Cohort 4 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 2 hr post-dose | 0 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 4 hr post-dose | 0 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 24 hr post-dose | 0 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 2 hr post-dose | 0 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 1, 1 hr post-dose | 0 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 4 hr post-dose | 0 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 24 hr post-dose | 0 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 12 hr post-dose | 7 Differentially expressed genes |
| Multiple Single Dose Cohort 5 | Number of Differentially Expressed Genes From Whole Blood Samples | Day 6, 8 hr post-dose | 6 Differentially expressed genes |