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

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ClinicalTrials.gov Identifier: NCT02994732
Recruitment Status : Completed
First Posted : December 16, 2016
Results First Posted : June 17, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
BioMed Valley Discoveries, Inc

Tracking Information
First Submitted Date  ICMJE November 14, 2016
First Posted Date  ICMJE December 16, 2016
Results First Submitted Date  ICMJE April 24, 2018
Results First Posted Date  ICMJE June 17, 2019
Last Update Posted Date June 17, 2019
Actual Study Start Date  ICMJE January 2017
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax [ Time Frame: 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 [ Time Frame: Collected over 5 days ]
    peak (maximum) concentration
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2 [ Time Frame: Collected over 15 days ]
    Elimination half-life
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC [ Time Frame: 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 [ Time Frame: Collected over 15 days ]
    Oral Clearance (CL/F)
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F [ Time Frame: Collected over 15 days ]
    Apparent volume of distribution (V/F)
  • Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces) [ Time Frame: Collected over 15 days ]
    Percent of dose excreted in feces
  • Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine) [ Time Frame: Collected over 15 days ]
    Percent of dose excreted in urine
  • Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12 [ Time Frame: Collected in 12 hrs ]
    AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation
  • Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24 [ Time Frame: Collected in 24 hrs ]
    AUC from time zero to 24 hrs
Original Primary Outcome Measures  ICMJE
 (submitted: December 13, 2016)
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax [ Time Frame: Collected over 15 days ]
    Time to peak concentration (Tmax)
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax [ Time Frame: Collected over 15 days ]
    peak (maximum) concentration
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2 [ Time Frame: Collected over 15 days ]
    Elimination half-life
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC [ Time Frame: Collected over 15 dyas ]
    Area under Curve (AUC)
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F [ Time Frame: Collected over 15 days ]
    Oral Clearance (CL/F)
  • Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F [ Time Frame: Collected over 15 days ]
    Apparent volume of distribution (V/F)
  • Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces) [ Time Frame: Collected over 15 days ]
    Percent of dose excreted in feces
  • Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine) [ Time Frame: Collected over 15 days ]
    Percent of dose excreted in urine
  • Pharmacokinetics of BVD-523 (in urine) CLR [ Time Frame: Collected over 15 days ]
    Renal clearance (CLR)
  • Excretion rate of 14C-labeled BVD-523 (radioactivity in vomit, if applicable) [ Time Frame: Collected in 15 days ]
    Percent of dose in vomit, if applicable
  • Metabolite identification of BVD-523 in plasma, urine and feces [ Time Frame: Collected in 15 days ]
  • cumulative whole blood: plasma ratio calculated for AUC0-tlast [ Time Frame: Collected in 15 days ]
    AUC from time zero to the last time point with concentration above the lower limit of quantitation
  • Cumulative whole blood: plasma ratio calculated for AUCinf [ Time Frame: Collected in 15 days ]
    AUC from time zero to infinity
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
Treatment-related Adverse Events [ Time Frame: 27 days ]
Any treatment-emergent adverse events related or likely related to study treatment
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2016)
Treatment-related Adverse Events [ Time Frame: 27 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Absorption, Metabolism and Excretion (AME) of Single Dose Radiolabeled BVD-523 in Volunteers
Official Title  ICMJE A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-BVD-523 Following Single Oral Dose Administration in Healthy Male Subjects
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Healthy
Intervention  ICMJE 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 Name: Ulixertinib
Study Arms  ICMJE 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).
Intervention: Drug: [14C]-BVD-523
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 13, 2016)
6
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 15, 2017
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02994732
Other Study ID Numbers  ICMJE 523HV001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BioMed Valley Discoveries, Inc
Study Sponsor  ICMJE BioMed Valley Discoveries, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Irene Mirkin, MD Covance
PRS Account BioMed Valley Discoveries, Inc
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP