Healthy Volunteers
Conditions
Keywords
Xevinapant, Absorption, Distribution, Metabolism and Excretion (ADME), Mass balance, Absolute bioavailability
Brief summary
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.
Interventions
DRUGRadiolabelled Xevinapant 200 mg (Oral Solution)
\[14C\]-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.
DRUGRadiolabelled Xevinapant 100 μg (IV Solution)
100 μg \[14C\]-xevinapant single dose administered as an IV bolus on Day 1, containing approximately 0.2 μCi \[7.4 kilobecquerel (kBq)\].
DRUGXevinapant 200 mg (Oral Solution)
Xevinapant 200 mg administered as an oral solution on Day 1 of Part 2 in fasted conditions
Sponsors
Debiopharm International SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bioavailability (F) of Xevinapant in Plasma | Up to Day 5 | Absolute Bioavailability (F) = (AUC0-infinity \[oral\]/ dose \[oral\]) /(AUC0-infinity \[IV\]/ dose \[IV\]) |
| 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 | — |
| 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 | — |
| 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Blood to Plasma Ratio of Xevinapant and Metabolite | Up to Day 8 |
Countries
United Kingdom
Outcome results
None listed