Healthy
Conditions
Brief summary
The primary objective of this study is to characterize the metabolic disposition, pharmacokinetics (PK), and routes of elimination of \[14C\]-labeled BVD-523 after administration of a single, oral dose to healthy male subjects. The secondary objective of this study is to evaluate the safety and tolerability of a single oral dose of \[14C\]-labeled BVD-523 in healthy male subjects.
Detailed description
This study will be an open-label, absorption, metabolism, and excretion study of \[14C\]-BVD-523 administered as a 600-mg (approximately 200 µCi) oral dose to 6 healthy male subjects following a 2-hour fast from food (not including water) that follows breakfast.
Interventions
DRUG[14C]-BVD-523
\[14C\]-BVD-523 administered as a 600-mg (approximately 200 µCi) oral dose to 6 healthy male subjects following a 2-hour fast from food (not including water) that follows breakfast.
Sponsors
BioMed Valley Discoveries, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Males, between 18 and 65 years of age, inclusive, at Screening * Have a body mass index range of 18.5 to 32.0 kg/m2, inclusive, at Screening * In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs measurements at Screening or Check-in and PE findings at Check-in as determined by the Investigator (or designee) * Clinical laboratory evaluations (including clinical chemistry panel \[fasted at least 8 hours\], hematology/complete blood count \[CBC\], and urinalysis \[UA\] within the reference range for the test laboratory at Screening and Check-in, unless deemed not clinically significant by the Investigator (or designee) * Negative test for selected drugs of abuse and cotinine at Screening (does not include alcohol) and at Check-in (does include alcohol) * Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens at Screening * Males will be surgically sterile for at least 90 days (confirmed by documented azoospermia) or, when sexually-active with female partners of child-bearing potential, will agree to use contraception as detailed in Section 6.3.3 from Check-in until 90 days following Discharge * Males must be willing to refrain from sperm donation from Check-in to 90 days from day of dosing * Able to comprehend and willing to sign an ICF * A minimum of 1 bowel movement per day.
Exclusion criteria
* Significant history or clinical manifestation of any metabolic, allergic, infectious, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator \[or designee\]) prior to Check-in * History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) prior to Check-in * History of stomach or intestinal surgery or resection that could alter absorption or excretion of orally administered drugs prior to Check-in except appendectomy, and hernia repair will be allowed if it was not associated with; * History of Gilbert's Syndrome * History or presence of an abnormal ECG that, in the Investigator's (or designee's) opinion, is clinically significant * History of alcoholism or drug addiction within 1 year prior to Check-in * History of nicotine use within 6 months prior to Check-in or positive cotinine at Screening or Check-in * Participation in more than 1 other radiolabeled investigational study drug trial within 12 months prior to Check-in. The previous radiolabeled study drug must have been received more than 6 months prior to Check-in for this study and the total exposure from this study and the previous study will be within the recommended levels considered safe, per United States (US) Title 21 Code of Federal Regulations (CFR) 361.1 (eg, less than 3,000 mrem whole body annual exposure) * Exposure to significant radiation (eg, serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to Check-in * Use of any drugs or substances known to be strong inhibitors or strong inducers of CYP3A enzyme within 30 days prior to study drug administration, unless otherwise stated, and throughout the study * Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days prior to Check-in, whichever is longer * Use of any prescription medications/products within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee) * Use of any over-the-counter, nonprescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee) * Poor peripheral venous access prior to Check-in * Donation of whole blood from 56 days prior to Screening through Discharge, inclusive, or of plasma from 30 days prior to Screening through Discharge, inclusive * Receipt of blood products within 2 months prior to Check-in * Any acute or chronic condition that, in the opinion of the Investigator (or designee), would limit the subject's ability to complete or participate in this clinical study * Any other unspecified reason that, in the opinion of the Investigator (or designee) or Sponsor, make the subject unsuitable for enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24 | Collected in 24 hrs | AUC from time zero to 24 hrs |
| Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine) | Collected over 15 days | Percent of dose excreted in urine |
| Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F | Collected over 15 days | Apparent volume of distribution (V/F) |
| Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces) | Collected over 15 days | Percent of dose excreted in feces |
| Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax | Collected over 5 days | Time to peak concentration (Tmax), PK blood samples were taken at the following time points 0 (predose), 30 min, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours post dose. |
| Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax | Collected over 5 days | peak (maximum) concentration |
| Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2 | Collected over 15 days | Elimination half-life |
| Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC | Collected over 15 dyas | Area under Curve (AUC), 0-24 hr |
| Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F | Collected over 15 days | Oral Clearance (CL/F) |
| Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12 | Collected in 12 hrs | AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related Adverse Events | 27 days | Any treatment-emergent adverse events related or likely related to study treatment |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Study Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Single Arm Study |
|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 16.6 |
| BMI | 24.9 kg/m^2 STANDARD_DEVIATION 2.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12
AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation
Time frame: Collected in 12 hrs
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12 | 0.464 hr*ng/ml | Standard Deviation 0.0354 |
Primary
Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24
AUC from time zero to 24 hrs
Time frame: Collected in 24 hrs
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24 | 0.409 hr*ng/ml | Standard Deviation 0.0297 |
Primary
Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces)
Percent of dose excreted in feces
Time frame: Collected over 15 days
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces) | 82 %of radioactive dose of [14C-BVD523 | Standard Deviation 4.72 |
Primary
Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine)
Percent of dose excreted in urine
Time frame: Collected over 15 days
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine) | 14.8 % of radioactive dose of [14C-BVD523 | Standard Deviation 4.79 |
Primary
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC
Area under Curve (AUC), 0-24 hr
Time frame: Collected over 15 dyas
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC | 8480 hr*ng/ml | Standard Deviation 3600 |
Primary
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F
Oral Clearance (CL/F)
Time frame: Collected over 15 days
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F | 73 L/hr | Standard Deviation 35.1 |
Primary
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax
peak (maximum) concentration
Time frame: Collected over 5 days
Population: All 6 subjects enrolled
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax | 1110 ng/ml | Standard Deviation 619 |
Primary
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2
Elimination half-life
Time frame: Collected over 15 days
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2 | 8.75 hr | Standard Deviation 3.57 |
Primary
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax
Time to peak concentration (Tmax), PK blood samples were taken at the following time points 0 (predose), 30 min, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours post dose.
Time frame: Collected over 5 days
Population: All enrolled subjects
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax | 2.57 hr | Standard Deviation 3 |
Primary
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F
Apparent volume of distribution (V/F)
Time frame: Collected over 15 days
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F | 899 L | Standard Deviation 463 |
Secondary
Treatment-related Adverse Events
Any treatment-emergent adverse events related or likely related to study treatment
Time frame: 27 days
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental [14C] -BVD-523 600mg Single Dose | Treatment-related Adverse Events | 2 Participants |