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

NCT02994732 | Completed Phase 1 Results

• 1 other identifier: 523HV001
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (1)

• Treatment-related Adverse Events

  27 days

Study Arms (1)

[14C]-BVD-523 600mg single dose

EXPERIMENTAL

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

Interventions

[14C]-BVD-523 DRUG

\[14C\]-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.

Also known as: Ulixertinib

[14C]-BVD-523 600mg single dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• BioMed Valley Discoveries, Inc: lead

MeSH Terms

Interventions

ulixertinib

Results Point of Contact

• Title: Associate Director of Translational Sciences
• Organization: Biomed Valley Discoveries

Dknoerzer@biomed-valley.com

636-887-6429

Study Officials

• Irene Mirkin, MD

  Covance

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: December 16, 2016
• Study Start: January 1, 2017
• Primary Completion: February 1, 2017
• Study Completion: May 15, 2017
• Last Updated: June 17, 2019
• Results First Posted: June 17, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share