This is a single-centre, open-label, non-randomised, single oral dose study in healthy male subjects. It is planned to enrol a single cohort of 6 healthy male subjects to ensure data in 4 evaluable subjects. Each subject will receive a single administration of 120 mg \[14C\] varlitinib oral suspension containing not more than (NMT) 2.9 MBq (79 µCi), in the fed state.
Subjects will be screened for eligibility to participate in the study up to 28 days before dosing. Subjects will be admitted to the clinical unit on the evening prior to IMP administration (Day 1) and will fast overnight for a minimum of 8 h. Subjects will be dosed on the morning of Day 1 following a light breakfast, and will remain resident in the clinic until up to 240 h after dosing (Day 11). It is planned that subjects will be released as a group when all subjects have achieved a mass balance cumulative recovery of \>90%, or if \<1% of the dose administered has been collected in urine and faeces within 2 separate, consecutive 24 h periods. In this case, collection of all samples (blood, urine and faeces) will cease and the subjects will undergo discharge assessments. If this criterion has not been met by all subjects on Day 11, the residency period may be extended by a further 48 h maximum (up to Day 13). If the criterion is still not met by Day 13, or if additional residency is not considered appropriate or necessary, then home collections of urine and/or faeces may be requested at the discretion of the investigator for individual subjects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
6
\[14C\]-Varlitinib
Quotient Clinical Ltd
Nottingham, United Kingdom
Mass balance recovery after a single oral dose of [14C] varlitinib
Mass balance recovery of \[14C\] varlitinib recovered in urine, faeces, and all excreta
Time frame: Assessments will be made up to 13 days postdose
Metabolite profiling and structural identification of metabolites in plasma, urine and faeces
Identification of the chemical structure of metabolites
Time frame: Assessments will be made up to 13 days postdose
Routes and rates of elimination of [14C] varlitinib
Amount \[14C\] varlitinib excreted for urine and faeces
Time frame: Assessments will be made up to 13 days postdose
Determination of the chemical structure of the "major" metabolites of [14C] varlitinib
Identification of the chemical structure of each metabolite accounting for greater than 10%
Time frame: Assessments will be made up to 13 days postdose
Evaluation of whole blood:plasma concentration ratios for total radioactivity
Time frame: Assessments will be made up to 13 days postdose
PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
Peak Plasma Concentration (Cmax)
Time frame: Assessments will be made up to 13 days postdose
PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
Area under the plasma concentration versus time curve (AUC)
Time frame: Assessments will be made up to 13 days postdose
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PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
Half life
Time frame: Assessments will be made up to 13 days postdose
PK of total radioactivity and varlitinib in plasma following a single oral dose of [14C] varlitinib
The time from dosing at which Cmax was apparent
Time frame: Assessments will be made up to 13 days postdose
Collect additional information on the safety and tolerability of varlitinib
Number of participants with abnormal laboratory values and/or adverse events
Time frame: Assessments will be made up to 13 days postdose