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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Radiolabelled Xevinapant 200 mg (Oral Solution); Drug: Radiolabelled Xevinapant 100 μg (IV Solution); Drug: Xevinapant 200 mg (Oral Solution)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Labcorp Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2021
• Primary Completion (Actual): November 9, 2021
• Study Completion (Actual): November 9, 2021

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: July 2, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): December 27, 2021
• Last Update Submitted That Met QC Criteria: December 23, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Mass balance; Xevinapant; Absorption, Distribution, Metabolism and Excretion (ADME); Absolute bioavailability
• Additional Relevant MeSH Terms: Pharmaceutical Solutions
• Other Study ID Numbers: Debio 1143-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No