Clinical trial NCT04436562: Study of the Absorption, Metabolism, and Excretion Following a Single Dose of [14C]-Poziotinib in Healthy Male Subjects
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy Volunteers
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2020-06-18
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of [14C]-Poziotinib, Metabolites M1 and M2
timeFrame: 1-15 days
measure: Cmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
timeFrame: 1-15 days
measure: Time to Attain Maximum Observed Plasma Concentration (Tmax) of [14C]-Poziotinib, Metabolites M1 and M2
timeFrame: 1-15 days
measure: Tmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
timeFrame: 1-15 days
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC[last]) of [14C]-Poziotinib, Metabolites M1 and M2
timeFrame: 1-15 days
measure: AUC(last) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
timeFrame: 1-15 days
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of [14C]-Poziotinib, Metabolites M1 and M2
timeFrame: 1-15 days
measure: AUC(inf) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
timeFrame: 1-15 days
measure: Percentage of AUCinf Derived by Extrapolation (%AUCext) of [14C]-Poziotinib, Metabolites M1 and M2
timeFrame: 1-15 days
measure: %AUCext of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
timeFrame: 1-15 days
measure: Apparent Terminal Elimination Half-Life (t1/2) of [14C]-Poziotinib, Metabolites M1 and M2
timeFrame: 1-15 days
measure: t1/2 of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
timeFrame: 1-15 days
measure: Elimination Rate Constant (λz, or kel) of [14C]-Poziotinib, Metabolites M1 and M2
timeFrame: 1-15 days
measure: λz, or kel of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
timeFrame: 1-15 days
measure: Apparent Volume of Distribution (VZ/F) During Terminal Phase of [14C]-Poziotinib
timeFrame: 1-15 days
measure: Apparent Oral Clearance (CL/F) of [14C]-Poziotinib
timeFrame: 1-15 days
measure: Whole Blood : Plasma Concentration Ratios of Total Radioactivity of [14C]-Poziotinib
timeFrame: 1-15 days
measure: Total Radioactivity of Cumulative Amount Excreted in Urine (Aeu)
timeFrame: 1-15 days
measure: Total Radioactivity of Fraction of Dose Excreted in Urine (feu)
timeFrame: 1-15 days
measure: Total Radioactivity of Cumulative Amount Excreted in Feces (Aef)
timeFrame: 1-15 days
measure: Total Radioactivity of Fraction of Dose Excreted in Feces (fef)
timeFrame: 1-15 days
measure: Total Radioactivity of Cumulative Total Amount Excreted (Aetotal)
timeFrame: 1-15 days
measure: Total Radioactivity of Fraction of Dose Excreted in Urine and Feces (fetotal)
timeFrame: 1-15 days
measure: Poziotinib Metabolite Profiling and Identification in Plasma
timeFrame: 1-15 days
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: 1-15 days
measure: Number of Participants with Hematology, Clinical Chemistry, Urinalysis Laboratory Abnormalities
timeFrame: 1-15 days
measure: Number of Participants with 12-lead electrocardiograms (ECG) Abnormalities
timeFrame: 1-15 days
measure: Number of Participants with Vital Sign and Physical Examinations Abnormalities
timeFrame: 1-15 days
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit, Inc.
state: Wisconsin
Study officials:
affiliation: Spectrum Pharmaceuticals, Inc
name: Shanta Chawla, MD
role: STUDY_DIRECTOR
References: