Study of the Absorption, Metabolism, and Excretion Following a Single Dose of [14C]-Poziotinib in Healthy Male Subjects

Overview

This will be a Phase 1, open-label, nonrandomized, single-dose study in healthy male subjects to evaluate the Absorption, Metabolism, and Excretion of Poziotinib following a single oral dose of [14C]-poziotinib to healthy male subjects.

Full Title of Study: “Phase 1 Open-label Study of the Absorption, Metabolism, and Excretion of Poziotinib Following a Single Oral Dose of [14C]-Poziotinib in Healthy Male Subjects”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 17, 2020

Detailed Description

Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the dose administration. Subjects will be admitted into the Clinical Research Unit (CRU) on Day -1. On the morning of Day 1, all subjects will receive a single oral dose of 8 mg (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib in the fasted state. Subjects will be confined to the CRU until at least Day 8. Subjects will be discharged from the CRU on Day 8 if the following criteria are met: – ≥90% mass balance recovery in combined urine and feces, and – ≤1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 2 consecutive 24-hour periods in which fecal and urine samples are obtained. If these criteria are not met by Day 8, subjects will remain in the CRU until all discharge criteria are met up to a maximum of Day 15 in order to continue 24-hour blood, urine, and feces collections, unless otherwise agreed upon by the Sponsor and Investigator.

Interventions

  • Drug: [14C]-Poziotinib
    • Single oral administration of 8 mg (as the hydrocholoride salt) of [14C]-poziotinib

Arms, Groups and Cohorts

  • Experimental: Poziotinib
    • A single oral dose of 8 mg poziotinib as a capsule formulation (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib

Clinical Trial Outcome Measures

Primary Measures

  • Maximum Observed Plasma Concentration (Cmax) of [14C]-Poziotinib, Metabolites M1 and M2
    • Time Frame: 1-15 days
  • Cmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
    • Time Frame: 1-15 days
  • Time to Attain Maximum Observed Plasma Concentration (Tmax) of [14C]-Poziotinib, Metabolites M1 and M2
    • Time Frame: 1-15 days
  • Tmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
    • Time Frame: 1-15 days
  • Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC[last]) of [14C]-Poziotinib, Metabolites M1 and M2
    • Time Frame: 1-15 days
  • AUC(last) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
    • Time Frame: 1-15 days
  • Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of [14C]-Poziotinib, Metabolites M1 and M2
    • Time Frame: 1-15 days
  • AUC(inf) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
    • Time Frame: 1-15 days
  • Percentage of AUCinf Derived by Extrapolation (%AUCext) of [14C]-Poziotinib, Metabolites M1 and M2
    • Time Frame: 1-15 days
  • %AUCext of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
    • Time Frame: 1-15 days
  • Apparent Terminal Elimination Half-Life (t1/2) of [14C]-Poziotinib, Metabolites M1 and M2
    • Time Frame: 1-15 days
  • t1/2 of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
    • Time Frame: 1-15 days
  • Elimination Rate Constant (λz, or kel) of [14C]-Poziotinib, Metabolites M1 and M2
    • Time Frame: 1-15 days
  • λz, or kel of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
    • Time Frame: 1-15 days
  • Apparent Volume of Distribution (VZ/F) During Terminal Phase of [14C]-Poziotinib
    • Time Frame: 1-15 days
  • Apparent Oral Clearance (CL/F) of [14C]-Poziotinib
    • Time Frame: 1-15 days
  • Whole Blood : Plasma Concentration Ratios of Total Radioactivity of [14C]-Poziotinib
    • Time Frame: 1-15 days
  • Total Radioactivity of Cumulative Amount Excreted in Urine (Aeu)
    • Time Frame: 1-15 days
  • Total Radioactivity of Fraction of Dose Excreted in Urine (feu)
    • Time Frame: 1-15 days
  • Total Radioactivity of Cumulative Amount Excreted in Feces (Aef)
    • Time Frame: 1-15 days
  • Total Radioactivity of Fraction of Dose Excreted in Feces (fef)
    • Time Frame: 1-15 days
  • Total Radioactivity of Cumulative Total Amount Excreted (Aetotal)
    • Time Frame: 1-15 days
  • Total Radioactivity of Fraction of Dose Excreted in Urine and Feces (fetotal)
    • Time Frame: 1-15 days
  • Poziotinib Metabolite Profiling and Identification in Plasma
    • Time Frame: 1-15 days

Secondary Measures

  • Number of Participants with Adverse Events (AEs)
    • Time Frame: 1-15 days
  • Number of Participants with Hematology, Clinical Chemistry, Urinalysis Laboratory Abnormalities
    • Time Frame: 1-15 days
  • Number of Participants with 12-lead electrocardiograms (ECG) Abnormalities
    • Time Frame: 1-15 days
  • Number of Participants with Vital Sign and Physical Examinations Abnormalities
    • Time Frame: 1-15 days

Participating in This Clinical Trial

Key Inclusion Criteria:

  • Body mass index between 18.0 and 32.0 kg/m2, inclusive – In good health at Screening and/or at Check-in – Subjects must be surgically sterile for at least 90 days, or when sexually active with female partners of childbearing and non-childbearing potential will be required to use a male condom with spermicide from CRU Check-in until 90 days after discharge. Subjects are required to refrain from donation of sperm from CRU Check-in until 90 days after discharge – Able to comprehend and willing to sign an ICF and to abide by the study restrictions – History of at least 1 bowel movement per day Key Exclusion Criteria:

  • Stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs – Swallowing difficulties or ongoing diarrhea of any etiology – Participation in a clinical study involving an investigational drug in the past 30 days prior to dosing – Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in – Use or intend to use any prescription medications/products within 14 days prior to Check-in – Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in – Exposure to significant diagnostic or therapeutic radiation or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Spectrum Pharmaceuticals, Inc
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Shanta Chawla, MD, Study Director, Spectrum Pharmaceuticals, Inc

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