This is a non-randomised study in patients with advanced solid malignancies
The aim is to recruit approximately 8 patients with a minimum number of 4 pharmacokinetics (PK) evaluable patients. Each patient will be admitted to the study site pre-dose on Day -1 and will remain at the study site until at least Day 8. Patients will receive a single administration of \[14C\]adavosertib as an oral solution on Day 1. During this study, whole blood, plasma, urine, faeces, and vomit samples (if presented) will be collected at various time points to characterise the absorption, distribution, metabolism, excretion and PK of adavosertib. The duration of the residential period will be evaluated following treatment of the first patient and may be adjusted to ensure recovery of at least 90% of the total radioactivity following the dose of \[14C\]adavosertib and/or until less than 1% of dose is recovered in urine and/or faeces within a 24-hour period.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
2
Patients will receive a single administration of \[14C\]Adavosertib as an oral solution on Day 1.
Research Site
Manchester, United Kingdom
Amount and cumulative amount excreted and expressed as the percentage of the administered dose into the urine and faeces from time t1 to time t2
Assessment of the mass balance of total radioactivity, including the routes and rates of elimination following a single oral dose \[14C\]adavosertib.
Time frame: Urine and fecal samples collected from pre-dose to 168 hours post-dose
Renal clearance of radioactivity (CLR)
Assessment of renal clearance of adavosertib, including the routes and rates of elimination following a single oral dose \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Maximum observed plasma concentration (Cmax)
Assessment of Cmax of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Area under plasma concentration-time curve from time zero to infinity (AUCinf)
Assessment of AUCinf of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Area under the plasma concentration-time curve from zero to time of last quantifiable concentration (AUClast)
Assessment of AUClast of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Time to reach peak or maximum observed concentration following drug administration (tmax)
Assessment of tmax of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
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Terminal elimination rate constant (λz)
Assessment of λz of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Assessment of t½λz of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Assessment of CL/F of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Mean Residence Time of the unchanged drug in the systemic circulation (MRTinf)
Assessment of MRTinf of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Volume of distribution (apparent) at steady state following extravascular administration (Vss/F)
Assessment of Vss/F of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Assessment of Vz/F of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Ratio of AUCinf of plasma adavosertib relative to AUCinf of plasma total radioactivity [AUCinf Plasma:Total Plasma Ratio]
Assessment of AUCinf plasma adavosertib:Total plasma radioactivity ratio following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Ratio of AUCinf of whole blood total radioactivity to AUCinf of plasma total radioactivity [AUCinf Blood:Plasma Ratio]
Assessment of AUCinf Blood:Plasma Ratio total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Amount, cumulative amount, and cumulative percentage of unchanged adavosertib excreted into urine from time t1 to time t2
Assessment of unchanged adavosertib following a single oral dose of \[14C\]adavosertib.
Time frame: Urine collected from pre-dose to 168 hours post-dose
Renal clearance of adavosertib from plasma (CLR)
Assessment of CLR of adavosertib and total radioactivity following a single oral dose of \[14C\]adavosertib.
Time frame: From pre-dose to 168 hours post-dose
Number of patients with adverse events (AE) and serious AEs (SAE)
Assessment of the safety and tolerability of adavosertib following oral dosing in patients with advanced solid tumours.
Time frame: From screening (Day -28 to Day -1) until end of study (within 30 [±7] days of adavosertib dose)