A Study to Evaluate the Absorption, Metabolism, and Excretion and Absolute Bioavailability of Xevinapant in Healthy Male Participants

Study Overview
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Brief Summary
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The purpose of the study is to determine absorption, metabolism, and excretion of a single oral dose of [14C]-xevinapant. This information will enable assessment of absorption and clearance mechanisms of [14C]-xevinapant as well as identify metabolites. In addition, the study will allow to determine absolute bioavailability of xevinapant and understand its intravenous pharmacokinetics.

Official Title
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A Phase 1, Open-label, 2-part, Single-dose Study of the Absorption, Metabolism, and Excretion of Oral [14C]-Xevinapant, and Absolute Oral Bioavailability of Xevinapant in Healthy Male Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Radiolabelled Xevinapant 200 mg (Oral Solution)
* Drug: Radiolabelled Xevinapant 100 μg (IV Solution)
* Drug: Xevinapant 200 mg (Oral Solution)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Males of any race, between 35 and 65 years of age, inclusive. Part 2: Males of any race, between 18 and 65 years of age, inclusive Body mass index between 18.0 and 30.0 kilograms per meter square (kg/m^2), inclusive Weight between 50 kilograms (kg) and 110 kg, inclusive History of a minimum of 1 bowel movement per day. Willing to adhere to the prohibitions and restrictions specified in the study protocol 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 alcohol consumption of >21 units per week. One unit of alcohol equals 12 ounce (oz) [360 millilitre (mL)] beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing, or less than 5 times the half-life, whichever is longer, prior to administration of study drug Poor peripheral venous access Have participated in any clinical study involving a radiolabeled investigational product within 12 months prior to check-in.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiolabeled Xevinapant Oral Solution<br>Participants will receive: • single oral dose of [14C]-xevinapant, as an oral solution | Drug: Radiolabelled Xevinapant 200 mg (Oral Solution)<br>* [14C]-Xevinapant 200 mg administered as an oral solution on Day 1 of Part 1, containing approximately 100 microcurie (μCi) [3.7 megabecquerel (MBq)] in fasted conditions.<br>|
| Experimental: Radiolabeled Xevinapant Intravenous Solution + Xevinapant Oral Solution<br>Participants will receive: • single oral dose of xevinapant, as an oral solution followed by an IV bolus of [14C]-xevinapant, solution for infusion | Drug: Radiolabelled Xevinapant 100 μg (IV Solution)<br>* 100 μg [14C]-xevinapant single dose administered as an IV bolus on Day 1, containing approximately 0.2 μCi [7.4 kilobecquerel (kBq)].<br>Drug: Xevinapant 200 mg (Oral Solution)<br>* Xevinapant 200 mg administered as an oral solution on Day 1 of Part 2 in fasted conditions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mass Balance Recovery Measured Through Total Radioactivity Excreted in Expired Air, Urine and Feces |  | Up to Day 29 | 
| Area Under Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity); Time 0 to 24 Hours (AUC0-24); Time 0 to Last Quantifiable Concentration (AUC0-last) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma |  | Up to Day 29 | 
| Maximum Observed Concentration (Cmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma |  | Up to Day 29 | 
| Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma |  | Up to Day 29 | 
| Apparent Terminal Elimination Half-life (T1/2) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma |  | Up to Day 29 | 
| Apparent Volume of Distribution During Terminal Phase (Vz/F) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma |  | Up to Day 29 | 
| Apparent Total Clearance (CL/F) of Total Radioactivity in Blood and Plasma and of Xevinapant and Metabolite in Plasma |  | Up to Day 29 | 
| Renal Clearance (CLr) of Total Radioactivity, Xevinapant and Metabolite |  | Up to Day 29 | 
| Xevinapant Metabolite Concentrations in Urine, Feces, Blood and Plasma |  | Up to Day 8 | 
| Absolute Bioavailability (F) of Xevinapant in Plasma | Absolute Bioavailability (F) = (AUC0-infinity [oral]/ dose [oral]) /(AUC0-infinity [IV]/ dose [IV]) | Up to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood to Plasma Ratio of Xevinapant and Metabolite |  | Up to Day 8 | 
| Plasma Protein Binding Expressed as Fraction unbound, fu of Xevinapant |  | Up to Day 8 | 
| Safety and Tolerability as Measured by Number of Participants With Treatment-Emergent Adverse Events |  | Up to Day 29 | 
| Safety and Tolerability as Measured by Number of Participants With Clinically significant Laboratory Abnormalities |  | Up to Day 29 | 
| Safety and Tolerability as Measured by Number of Participants With Clinically significant 12-lead ECG Parameters Abnormalities |  | Up to Day 29 | 
| Safety and Tolerability as Measured by Number of Participants With Clinically significant Vital Signs Abnormalities |  | Up to Day 29 | 
| Safety and Tolerability as Measured by Number of Participants With Clinically significant Physical Examination Abnormalities |  | Up to Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xevinapant, Absorption, Distribution, Metabolism and Excretion (ADME), Mass balance, Absolute bioavailability