Healthy Volunteer
Conditions
Keywords
ASP3082, Setidegrasib, Pharmacokinetics, Healthy Volunteers
Brief summary
Setidegrasib (ASP3082) is being developed for certain cancers. In this study, the researchers want to understand how it is processed by the body in healthy male volunteers. To do this, \[14C\] which is a certain chemical (called a tracer, or radionuclide) has been added to setidegrasib. \[14C\] gives off radiation, but the dose is very low (about the same as the dose from an x-ray) and will leave the body within a few days. \[14C\] will be picked up by a scanner and will be used to follow setidegrasib through the body. \[14C\]setidegrasib will be given as 1 single injection slowly through a vein (infusion). The men will stay overnight in the clinic for at least 2 weeks. They will give regular blood, urine and stool samples during their stay and will be closely monitored. The men will return to the clinic about 1 week later for a final safety check.
Interventions
DRUG14C-labeled ASP3082
Intravenous infusion
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant is healthy and has no clinically significant medical conditions based on the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1. * Participant has regular bowel habits (i.e., at least 1 bowel movement per day). * Male participant: * Must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the investigational period and for 3 months after study intervention administration. * Must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 3 months after study intervention administration. * Must not donate sperm during the investigational period and for 3 months after investigational study intervention administration. * Participant agrees not to participate in another interventional study while participating in the present study. * Participant has a body mass index (BMI) range of 18.0 to 32.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
Exclusion criteria
* Participant has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease. * Participant has a history of malignancy within 2 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence). * Participant has had major surgery (e.g., requiring general anesthesia) within 90 days before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 5 half-lives (approximately 8 to 9 days) after the dose of study drug administration or end-of-study visit (ESV), whichever is longer. * Participant has previously undergone a cholecystectomy. * Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to day -1. * Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria within 2 years before screening. * Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome. * Participant has used any prescribed or nonprescribed drugs (including vitamins and natural and herbal remedies, e.g., St. John's Wort) in the 28 days prior to day -1, except for occasional use of acetaminophen (up to 2 g/day) and topical dermatological products (including corticosteroid products). * Participant has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 28 days prior to day -1. * Participant has received a coronavirus disease 2019 (COVID-19) vaccine within the 14 days prior to day -1 or will have a COVID-19 vaccine dose before the ESV. * Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening. * Participant has participated in more than 2 radiolabeled studies within 12 months prior to day -1 (participation in a previous radiolabeled study has to have been at least 4 months prior to day -1 where exposures are known to the investigator, or 6 months prior to day -1 where exposures are not known to the investigator). * Participant has any liver test result (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and total bilirubin \[TBL\]) ≥ 1.5 × upper limit of normal (ULN) on day -1. * Participant has clinically significant creatinine elevation. * Participant has any of the following conditions on day -1: mean pulse \< 45 or \> 90 bpm; mean systolic blood pressure (SBP) \> 140 mmHg; mean diastolic blood pressure (DBP) \> 90 mmHg (measurements taken in triplicate after participant has been resting in the supine position for at least 5 minutes; pulse measured automatically). If the mean blood pressure exceeds the limits above, 1 additional triplicate may be taken. * Participant has a mean corrected QT interval by Fridericia (QTcF) of \> 450 msec on day -1. * Participant tests positive for alcohol at screening or on day -1. * Participant tests positive for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) at screening or on day -1. * Participant tests positive for cannabinoids on day -1. * Participant has a positive serology test for hepatitis A virus (HAV) antibodies immunoglobulin M (IgM), hepatitis B (HBc) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening. * Participant has any condition, that makes the participant unsuitable for study participation. * Participant has exposure to significant diagnostic or therapeutic radiation (e.g., serial X ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to day -1. * Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used. * Participant has a history of smoking \> 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to day -1 or the participant tests positive for cotinine at screening or day -1. * Participant has a history of consuming \> 10 units of alcoholic beverages per week within 3 months prior to screening (Note: 1 unit = 12 ounces of beer, 5 ounces of wine, 1.5 ounce of spirits/hard liquor). * Participant has used any drugs of abuse (e.g., amphetamines, barbiturates, benzodiazepines, cocaine and/or opiates) within 3 months prior to day -1. * Participant has had significant blood loss, donated ≥ 1 unit (450 mL) of whole blood or donated plasma within 7 days prior to day -1 and/or received a transfusion of any blood or blood products within 60 days prior to day -1. * Participant has had previous exposure with ASP3082. * Participant is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of 14C-labeled ASP3082 (radioactivity in whole blood): area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf) | Up to 21 days | AUCinf will be recorded from the PK whole blood samples collected. |
| PK of 14C-labeled ASP3082 (radioactivity in whole blood): area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast) | Up to 21 days | AUClast will be recorded from the PK whole blood samples collected. |
| PK of 14C-labeled ASP3082 (radioactivity in whole blood): maximum concentration (Cmax) | Up to 21 days | Cmax will be recorded from the PK whole blood samples collected. |
| PK of 14C-labeled ASP3082 (radioactivity in plasma): AUCinf | Up to 21 days | AUCinf will be recorded from the PK plasma samples collected. |
| PK of 14C-labeled ASP3082 (radioactivity in plasma): AUClast | Up to 21 days | AUClast will be recorded from the PK plasma samples collected. |
| PK of 14C-labeled ASP3082 (radioactivity in plasma): Cmax | Up to 21 days | Cmax will be recorded from the PK plasma samples collected. |
| PK of 14C-labeled ASP3082 (radioactivity ratio of whole blood/plasma concentrations): radioactivity ratio of area under the concentration time curve in blood as compared to plasma (AUCblood/AUCplasma) | Up to 21 days | AUCblood/AUCplasma will be recorded from PK whole blood and plasma samples collected. |
| Excretion of 14C-labeled ASP3082 (radioactivity in urine): amount of administered dose excreted (Ae) | Up to 21 days | Ae will be recorded from urine samples collected. |
| Excretion of 14C-labeled ASP3082 (radioactivity in urine): percentage of administered dose excreted (Ae percentage) | Up to 21 days | Ae percentage will be recorded from urine samples collected. |
| Excretion of 14C-labeled ASP3082 (radioactivity in urine): cumulative (over more than 1 sampling interval) amount of administered dose excreted (CumAe) | Up to 21 days | CumAe will be recorded from urine samples collected. |
| Excretion of 14C-labeled ASP3082 (radioactivity in urine): renal clearance (CLr) | Up to 21 days | CLr will be recorded from urine samples collected. |
| Excretion of 14C-labeled ASP3082 (radioactivity in feces): Ae | Up to 21 days | Ae will be recorded from feces samples collected. |
| Excretion of 14C-labeled ASP3082 (radioactivity in feces): Ae percentage | Up to 21 days | Ae percentage will be recorded from feces samples collected. |
| Excretion of 14C-labeled ASP3082 (radioactivity in feces): CumAe | Up to 21 days | CumAe will be recorded from feces samples collected. |
| Excretion of 14C-labeled ASP3082 (combined radioactivity in urine and feces): Ae | Up to 21 days | Combined Ae will be recorded from urine and feces samples collected. |
| Excretion of 14C-labeled ASP3082 (combined radioactivity in urine and feces): Ae percentage | Up to 21 days | Combined Ae percentage will be recorded from urine and feces samples collected. |
| Excretion of 14C-labeled ASP3082 (combined radioactivity in urine and feces): CumAe | Up to 21 days | Combined CumAe will be recorded from urine and feces samples collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) | Up to 30 days | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention |
| Number of Participants with laboratory value abnormalities and/or AEs | Up to 30 days | Number of participants with potentially clinically significant laboratory values. |
| Number of Participants with vital sign abnormalities and/or AEs | Up to 30 days | Number of participants with potentially clinically significant vital sign values. |
| Number of Participants with electrocardiogram (ECG) abnormalities and/or AEs | Up to 30 days | Number of participants with potentially clinically significant ECG values. |
| Metabolite identification of ASP3082 in plasma | Up to 21 days | Identification of metabolites in plasma. |
| Metabolite identification of ASP3082 in urine | Up to 21 days | Identification of metabolites in urine. |
| Metabolite identification of ASP3082 in feces | Up to 21 days | Identification of metabolites in feces. |
Contacts
CONTACTAstellas Pharma Global Development, Inc.
STUDY_DIRECTORMedical Director
Astellas Pharma Global Development, Inc.
Outcome results
None listed