The purpose of the study is to understand how the study medicine ARV-471 is processed in the body of healthy males and females who do not have the potential to have children. This study is seeking for participants who: * are healthy males and females who do not have the potential to have children. * are 18 years of age or older. * weigh more than 110 pounds.
About 6 participants each will receive a single dose of either type of ARV-471. They are taken as liquid suspensions by mouth. Participants will stay in the study site for about 13 days and 12 nights.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
12
Participants will receive a single dose of \[phenyl-14C\]ARV-471 by mouth
Participants will receive a single dose of \[oxoisoindolin-14C\]ARV-471 by mouth
PPD Phase I Clinic
Austin, Texas, United States
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of ARV-471 and ARV-473 (an epimer of ARV-471)
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of ARV-471 and ARV-473 (an epimer of ARV-471)
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of ARV-471 and ARV-473 (an epimer of ARV-471)
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ARV-471 and ARV-473 (an epimer of ARV-471)
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Plasma Decay Half-Life (t1/2) of ARV-471 and ARV-473 (an epimer of ARV-471)
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Apparent Oral Clearance (CL/F) of ARV-471
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Apparent Volume of Distribution (Vz/F) of ARV-471
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Renal Clearance (CLr) of ARV-471 and ARV-473 (an epimer of ARV-471)
Time frame: Day 1 at intervals of 0-6 hours, 6-12 hours, 12-24 hours, and at each subsequent 24-hour interval starting on Day 2 until Day 12 or the discharge day
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Cumulative Amount of Drug Recovered Unchanged in Urine (Ae) of ARV-471 and ARV-473 (an epimer of ARV-471) and the Total Amounts Expressed as a Percent of Dose (Ae(%))
Time frame: Day 1 at intervals of 0-6 hours, 6-12 hours, 12-24 hours, and at each subsequent 24-hour interval starting on Day 2 until Day 12 or the discharge day
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Total Radioactivity
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Total Radioactivity
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Total Radioactivity
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Plasma Decay Half-Life (t1/2) of Total Radioactivity
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Apparent Oral Clearance (CL/F) of Total Radioactivity
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Apparent Volume of Distribution (Vz/F) of Total Radioactivity
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Cumulative recovery (%) of radioactivity in urine and feces
Time frame: Starting on Day 1 to Day 12 or the discharge day
Metabolite identification/profiling in feces, plasma and urine
Time frame: Day 1 pre-dose, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE is defined as one of the following: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. AEs include all SAEs and non-SAEs.
Time frame: Time the participant provides informed consent through and including follow-up contact occurring 28 to 35 calendar days after the last administration of the study intervention.
Number of Participants With Clinical Laboratory Abnormalities
Following parameters were analyzed for laboratory examination: hematology(hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function(aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid, cystatin C);electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry(glucose); urinalysis (dipstick\[decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, bilirubin\], microscopy.
Time frame: Baseline up to Day 12/Discharge
Number of Participants With Electrocardiogram (ECG) Abnormalities
ECG abnormalities criteria include a) a post dose QTcF is increased by \>60 ms from the baseline and is \>450 ms; or b) an absolute QTcF value is \>500ms for any scheduled ECG.
Time frame: Baseline up to Day 12/Discharge
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Blood pressure and pulse rate will be performed following at least a 5-minute rest in a supine position.
Time frame: Baseline up to Day 12/Discharge
Number of Participants With Abnormalities in Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems.
Time frame: Baseline up to Day 12/Discharge