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

NCT04962724 | Completed Phase 1

• 1 other identifier: Debio 1143-108
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Xevinapant; Absorption, Distribution, Metabolism and Excretion (ADME); Mass balance; Absolute bioavailability

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (7)

• 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

Study Arms (2)

Radiolabeled Xevinapant Oral Solution

EXPERIMENTAL

Participants will receive: • single oral dose of \[14C\]-xevinapant, as an oral solution

Drug: Radiolabelled Xevinapant 200 mg (Oral Solution)

Radiolabeled Xevinapant Intravenous Solution + Xevinapant Oral Solution

EXPERIMENTAL

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); Drug: Xevinapant 200 mg (Oral Solution)

Interventions

Radiolabelled Xevinapant 200 mg (Oral Solution) DRUG

\[14C\]-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.

Radiolabeled Xevinapant Oral Solution

Radiolabelled Xevinapant 100 μg (IV Solution) DRUG

100 μg \[14C\]-xevinapant single dose administered as an IV bolus on Day 1, containing approximately 0.2 μCi \[7.4 kilobecquerel (kBq)\].

Radiolabeled Xevinapant Intravenous Solution + Xevinapant Oral Solution

Xevinapant 200 mg (Oral Solution) DRUG

Xevinapant 200 mg administered as an oral solution on Day 1 of Part 2 in fasted conditions

Radiolabeled Xevinapant Intravenous Solution + Xevinapant Oral Solution

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (1)

Labcorp Clinical Research Unit

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Interventions

Solutions; Infusions, Intravenous

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: July 15, 2021
• Study Start: August 2, 2021
• Primary Completion: November 9, 2021
• Study Completion: November 9, 2021
• Last Updated: December 27, 2021

Record last verified: 2021-12

Locations

GB (1)