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

A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-BVD-523 Following Single Oral Dose Administration in Healthy Male Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: [14C]-BVD-523

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]-BVD-523 600mg single dose; Open-label, nonrandomized, 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 at least an 8-hour fast from food (not including water).	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.; Other Names: Ulixertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Collected over 5 days
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax	peak (maximum) concentration	Collected over 5 days
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2	Elimination half-life	Collected over 15 days
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC	Area under Curve (AUC), 0-24 hr	Collected over 15 dyas
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F	Oral Clearance (CL/F)	Collected over 15 days
Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F	Apparent volume of distribution (V/F)	Collected over 15 days
Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces)	Percent of dose excreted in feces	Collected over 15 days
Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine)	Percent of dose excreted in urine	Collected over 15 days
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	Collected in 12 hrs
Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24	AUC from time zero to 24 hrs	Collected in 24 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related Adverse Events	Any treatment-emergent adverse events related or likely related to study treatment	27 days

Collaborators and Investigators

• Sponsor: BioMed Valley Discoveries, Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): May 15, 2017

Study Registration Dates

• First Submitted: November 14, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimate): December 16, 2016

Study Record Updates

• Last Update Posted (Actual): June 17, 2019
• Last Update Submitted That Met QC Criteria: March 14, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 523HV001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO