Clinical trial NCT04962724: A Study to Evaluate the Absorption, Metabolism, and Excretion and Absolute Bioavailability of Xevinapant in Healthy Male Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Xevinapant
Absorption, Distribution, Metabolism and Excretion (ADME)
Mass balance
Absolute bioavailability
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2021-07-15
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mass Balance Recovery Measured Through Total Radioactivity Excreted in Expired Air, Urine and Feces
timeFrame: Up to Day 29
measure: 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
timeFrame: Up to Day 29
measure: Maximum Observed Concentration (Cmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
timeFrame: Up to Day 29
measure: Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
timeFrame: Up to Day 29
measure: Apparent Terminal Elimination Half-life (T1/2) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
timeFrame: Up to Day 29
measure: Apparent Volume of Distribution During Terminal Phase (Vz/F) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
timeFrame: Up to Day 29
measure: Apparent Total Clearance (CL/F) of Total Radioactivity in Blood and Plasma and of Xevinapant and Metabolite in Plasma
timeFrame: Up to Day 29
measure: Renal Clearance (CLr) of Total Radioactivity, Xevinapant and Metabolite
timeFrame: Up to Day 29
measure: Xevinapant Metabolite Concentrations in Urine, Feces, Blood and Plasma
timeFrame: Up to Day 8
measure: Absolute Bioavailability (F) of Xevinapant in Plasma
timeFrame: Up to Day 5
Secondary outcomes:
measure: Blood to Plasma Ratio of Xevinapant and Metabolite
timeFrame: Up to Day 8
measure: Plasma Protein Binding Expressed as Fraction unbound, fu of Xevinapant
timeFrame: Up to Day 8
measure: Safety and Tolerability as Measured by Number of Participants With Treatment-Emergent Adverse Events
timeFrame: Up to Day 29
measure: Safety and Tolerability as Measured by Number of Participants With Clinically significant Laboratory Abnormalities
timeFrame: Up to Day 29
measure: Safety and Tolerability as Measured by Number of Participants With Clinically significant 12-lead ECG Parameters Abnormalities
timeFrame: Up to Day 29
measure: Safety and Tolerability as Measured by Number of Participants With Clinically significant Vital Signs Abnormalities
timeFrame: Up to Day 29
measure: Safety and Tolerability as Measured by Number of Participants With Clinically significant Physical Examination Abnormalities
timeFrame: Up to Day 29
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Labcorp Clinical Research Unit
Study officials:
References: