This Phase I, open-label study aims to study to absolute bioavailability of Saruparib (AZD5305) and the absorption, distribution, metabolism and excretion (ADME) of \[14C\]-Saruparib in patients with advanced solid malignancies. This will be done on an inpatient basis in 2 parts (single-dose oral administration with radiolabeled microtracer in Part A, single-dose IV radiolabeled administration in Part B) during which samples will be obtained of plasma, urine, feces and vomitus (where applicable).
This is an open-label, 2-part study in participants with advanced solid malignancies and will be conducted at multiple study sites. Participants will be assessed for study eligibility prior to admission to the study site during a 28-day screening period. Participants will take part in both Parts A and B of the study. Part A will assess the absolute bioavailability and evaluate the PK parameters of oral Saruparib and a radiolabelled IV microdose of \[14C\]-Saruparib Participants will be admitted to the study site pre-dose of Part A and will remain resident at the study site for PK sampling and safety assessments. A washout period will be observed between doses of Saruparib in Parts A and B. Part B will assess the ADME of oral \[14C\]-Saruparib. Participants will be readmitted to the study site for Part B and will remain resident at the study site for excreta (urine, faeces, and any vomitus) collections, PK sampling, and safety assessments. Participants may be discharged from the study site prior to the last indicated day if both the following discharge criteria are met: 1. ≥ 90% mass balance recovery, and 2. \< 1% of the total radioactive dose is recovered in combined excreta (urine and faeces) in 2 consecutive 24-hour periods. Participants will return to the study site for a Follow-up Visit after the last dose of Saruparib which will include routine safety assessments. After the completion of Parts A and B, and following the Follow-up Visit, participants may be allowed further access to Saruparib. Additional safety data collection will be conducted.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
PARP-inhibitor
IV radiolabeled microtracer
IV radiolabeled PARP inhibitor
Research Site
Liverpool, United Kingdom
RECRUITINGResearch Site
Manchester, United Kingdom
RECRUITINGAbsolute bioavailability (F) of Saruparib
Absolute bioavailability (F) of Saruparib
Time frame: Day 4
Total radioactivity recovery in urine and faeces
Total radioactivity recovery in urine and faeces
Time frame: Day 8
Pharmacokinetics of Saruparib(Part B)
AUCinf
Time frame: Day 8
PK parameters characterized by AUCinf
AUCinf
Time frame: Day 4
Ratio of AUCinf of plasma Saruparib relative to AUCinf of metabolite
Ratio of AUCinf of plasma Saruparib relative to AUCinf of metabolite
Time frame: Day 4
Mass balance parameters as characterized by amount excreted and cumulative amount excreted in urine, faeces and total (urine and faeces combined)
Cumulative amount excreted in urine, faeces and total (urine and faeces combined)
Time frame: Day 8
Amount excreted and cumulative amount excreted in urine, faeces and total (urine and faeces combined) expressed as a percentage of the administered dose
Amount excreted and cumulative amount excreted in urine, faeces and total (urine and faeces combined) expressed as a percentage of the administered dose.
Time frame: Day 8
Pharmacokinetics of Saruparib(Part B)
AUClast
Time frame: Day 8
Pharmacokinetics of Saruparib(Part B)
AstraZeneca Clinical Study Information Center
CONTACT
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NONE
Enrollment
8
Cmax
Time frame: Day 8
Pharmacokinetics of Saruparib(Part B)
tmax
Time frame: Day 8
Pharmacokinetics of Saruparib(Part B)
t1/2(lambda)z
Time frame: Day 8
Pharmacokinetics of Saruparib(Part B)
Ratio of AUCinf of plasma Saruparib relative to AUCinf of plasma total radioactivity
Time frame: Day 8
Pharmacokinetics of Saruparib(Part B)
Ratio of AUCinf of whole blood total radioactivity relative to AUCinf of plasma total radioactivity
Time frame: Day 8
PK parameters characterized by AUClast
AUClast
Time frame: Day 4
PK parameters characterized by Cmax
Cmax
Time frame: Day 4
PK parameters characterized by tmax
tmax
Time frame: Day 4
PK parameters characterized by t1/2(lambda)z
t1/2(lambda)z
Time frame: Day 4
Metabolic profiling of a single oral dose of [14C]-Saruparib (Part B)
Determining mass balance parameters following oral administration of a therapeutic dose containing 20uCi of 14C-AZD5305 followed by metabolite profiling and identification in plasma, urine, and feces to quantify the 14C-AZD5305 related material in each matrix to satisfy MIST considerations.
Time frame: Day 8
Characterize the safety of Saruparib in participants with advanced solid malignancies by incidence and severity of AEs, laboratory abnormalities, 12-lead ECG abnormalities, vital signs abnormalities, physical examination findings
incidence and severity of AEs, -incidence of laboratory abnormalities (based on hematology, clinical chemistry, and urinalysis test results), -12-lead ECG abnormalities, vital signs abnormalities, physical examination findings
Time frame: Day 14