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

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

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit, Inc.

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: Poziotinib; A single oral dose of 8 mg poziotinib as a capsule formulation (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib	Drug: [14C]-Poziotinib; Single oral administration of 8 mg (as the hydrocholoride salt) of [14C]-poziotinib

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2020
• Primary Completion (Actual): July 17, 2020
• Study Completion (Actual): July 17, 2020

Study Registration Dates

• First Submitted: June 11, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Other Study ID Numbers: SPI-POZ-105

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No