Trial Outcomes & Findings for Absorption, Metabolism and Excretion (AME) of Single Dose Radiolabeled BVD-523 in Volunteers (NCT NCT02994732)

NCT ID: NCT02994732

Last Updated: 2019-06-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Collected over 5 days
• Results posted on: 2019-06-17

Participant Flow

Participant milestones

Measure	Experimental [14C] - BVD-523 600mg Single Dose Subjects received a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that followed breakfast. 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.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Absorption, Metabolism and Excretion (AME) of Single Dose Radiolabeled BVD-523 in Volunteers

Baseline characteristics by cohort

Measure	Single Arm Study n=6 Participants 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.
Age, Continuous	39.0 years STANDARD_DEVIATION 16.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
BMI	24.9 kg/m^2 STANDARD_DEVIATION 2.38 • n=5 Participants

PRIMARY outcome

Timeframe: Collected over 5 days

Population: All enrolled subjects

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.

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax

2.57 hr Standard Deviation 3.0

PRIMARY outcome

Timeframe: Collected over 5 days

Population: All 6 subjects enrolled

peak (maximum) concentration

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax

1110 ng/ml Standard Deviation 619

PRIMARY outcome

Timeframe: Collected over 15 days

Population: All enrolled subjects

Elimination half-life

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2

8.75 hr Standard Deviation 3.57

PRIMARY outcome

Timeframe: Collected over 15 dyas

Population: All enrolled subjects

Area under Curve (AUC), 0-24 hr

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC

8480 hr*ng/ml Standard Deviation 3600

PRIMARY outcome

Timeframe: Collected over 15 days

Population: All enrolled subjects

Oral Clearance (CL/F)

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F

73 L/hr Standard Deviation 35.1

PRIMARY outcome

Timeframe: Collected over 15 days

Population: All enrolled subjects

Apparent volume of distribution (V/F)

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F

899 L Standard Deviation 463

PRIMARY outcome

Timeframe: Collected over 15 days

Population: All enrolled subjects

Percent of dose excreted in feces

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces)

82 %of radioactive dose of [14C-BVD523 Standard Deviation 4.72

PRIMARY outcome

Timeframe: Collected over 15 days

Population: All enrolled subjects

Percent of dose excreted in urine

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine)

14.8 % of radioactive dose of [14C-BVD523 Standard Deviation 4.79

PRIMARY outcome

Timeframe: Collected in 12 hrs

Population: All enrolled subjects

AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12

0.464 hr*ng/ml Standard Deviation 0.0354

PRIMARY outcome

Timeframe: Collected in 24 hrs

Population: All enrolled subjects

AUC from time zero to 24 hrs

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24

0.409 hr*ng/ml Standard Deviation 0.0297

SECONDARY outcome

Timeframe: 27 days

Population: All enrolled subjects

Any treatment-emergent adverse events related or likely related to study treatment

Outcome measures

Measure

Experimental [14C] -BVD-523 600mg Single Dose n=6 Participants Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of \[14C\] labeled BVD-523 following a 2-hour fast that follows breakfast. 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.

Treatment-related Adverse Events

2 Participants

Adverse Events

Single Arm Study

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Single Arm Study n=6 participants at risk 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.
General disorders Fatigue	16.7% 1/6 • Number of events 1 • 27 days Adverse event definitions; assignment of severity, causality, action taken, and outcome; and procedures for reporting serious AEs (SAEs) are detailed in Appendix C of the protocol. None of the definitions differ from the clinicaltrials.gov definitions.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Number of events 1 • 27 days Adverse event definitions; assignment of severity, causality, action taken, and outcome; and procedures for reporting serious AEs (SAEs) are detailed in Appendix C of the protocol. None of the definitions differ from the clinicaltrials.gov definitions.

Additional Information

Associate Director of Translational Sciences

Biomed Valley Discoveries

Phone: 636-887-6429

Email: Dknoerzer@biomed-valley.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place