Primary Outcome Measures
- Total Radioactivity Recovery (fet1-t2) – Urine
- Total Radioactivity Recovery (fet1-t2) – Faeces
- Total Radioactivity – Plasma
- Total Radioactivity – Whole Blood
- Plasma Pharmacokinetic Parameters – Maximum observed concentration (Cmax)
- Plasma Pharmacokinetic Parameters – Time to Maximum Observed Concentration (Tmax)
- Plasma Pharmacokinetic Parameters – Terminal Elimination Half-life (t1/2)
- Plasma Pharmacokinetic Parameters – Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞)
- Plasma Pharmacokinetic Parameters – Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-tlast)
- Urinary Recovery – Percentage of the dose administered recovered over the time interval t1 to t2 (fet1-t2)
Secondary Outcome Measures
- Metabolic Profile & Identification – Bemcentinib – Plasma
- Metabolic Profile & Identification – Bemcentinib – Urine
- Metabolic Profile & Identification – Bemcentinib – Faeces
- Adverse Events
- Number of participants who report a change from normal range values for laboratory safety parameters (serum biochemistry, serum haematology or urinalysis) from first dose on Day 1 to study completion.
- Number of participants who report a change from normal range values for any of the associated 12-Lead ECG Parameters from first dose on Day 1 to study completion.
- Number of participants who report a change from normal range values for any of the vital signs parameters from first dose on Day 1 to study completion.
- Number of participants who report a change from normal with respect to physical examination parameters from first dose on Day 1 to study completion.
Inclusion Criteria
- Males of any race, between 35 and 55 years of age, inclusive.
- Body mass index between 18.0 and 32.0 kg/m2, inclusive, and a total body weight between 50 and 100 kg, inclusive.
- In good health, determined by no clinically significant findings from medical history, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert’s syndrome based on total and direct bilirubin] is not acceptable) at screening and check-in and from the physical examination at check-in, as assessed by the investigator (or designee).
- No clinically significant abnormalities in 12-lead ECG determined within 28 days before dose of IMP including average PR > 220 ms and QT interval corrected for heart rate using Fridericia’s formula >450 ms.
- No history of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia, left bundle branch block, or ventricular arrhythmia), atrial fibrillation, or history of familial long QT syndromes.
- Will agree to use contraception as detailed in the study protocol.
- Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
- History of a minimum of 1 bowel movement per day.
Exclusion Criteria
- Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
- History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
- Positive hepatitis panel and/or positive human immunodeficiency virus test.
Prior/concomitant therapy
- Administration of a COVID-19 vaccine in the past 30 days prior to dosing.
- Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John’s wort, within 30 days prior to check-in, unless deemed acceptable by the investigator (or designee).
- Use or intend to use any prescription medications/products within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee).
- Use or intend to use slow-release medications/products considered to still be active within 14 days prior to check-in, unless deemed acceptable by the investigator (or designee).
- Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to check-in, unless deemed acceptable by the investigator (or designee).
Prior/concurrent clinical study experience
- Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
- Subjects who have participated in any clinical study involving a radiolabeled investigational product within 12 months prior to check-in.
- Have previously completed or withdrawn from this study or any other study investigating bemcentinib, and have previously received bemcentinib.
Diet and lifestyle
- Alcohol consumption of > 28 units per week for males. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
- Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening or check-in.
- History of alcoholism or drug/chemical abuse within 2 years prior to check-in.
- Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or positive cotinine at screening or check-in.
- Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages within 7 days prior to check-in.
Other exclusions
- Receipt of blood products within 2 months prior to check-in.
- Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
- Poor peripheral venous access.
- Subjects with exposure to significant diagnostic or therapeutic radiation (eg, serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to check-in.
- Subjects who, in the opinion of the investigator (or designee), should not participate in this study.
