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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04962724
• Other study ID #: Debio 1143-108
• Status: Completed
• Phase: Phase 1
• Start date: August 2, 2021
• Est. completion date: November 9, 2021

Study information

• Verified date: December 2021
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 9, 2021
• Est. primary completion date: November 9, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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.
• 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)].
• Xevinapant 200 mg (Oral Solution)
Xevinapant 200 mg administered as an oral solution on Day 1 of Part 2 in fasted conditions

Locations

Country	Name	City	State
United Kingdom	Labcorp Clinical Research Unit	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mass Balance Recovery Measured Through Total Radioactivity Excreted in Expired Air, Urine and Feces		Up to Day 29
Primary	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
Primary	Maximum Observed Concentration (Cmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma		Up to Day 29
Primary	Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma		Up to Day 29
Primary	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
Primary	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
Primary	Apparent Total Clearance (CL/F) of Total Radioactivity in Blood and Plasma and of Xevinapant and Metabolite in Plasma		Up to Day 29
Primary	Renal Clearance (CLr) of Total Radioactivity, Xevinapant and Metabolite		Up to Day 29
Primary	Xevinapant Metabolite Concentrations in Urine, Feces, Blood and Plasma		Up to Day 8
Primary	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	Blood to Plasma Ratio of Xevinapant and Metabolite		Up to Day 8
Secondary	Plasma Protein Binding Expressed as Fraction unbound, fu of Xevinapant		Up to Day 8
Secondary	Safety and Tolerability as Measured by Number of Participants With Treatment-Emergent Adverse Events		Up to Day 29
Secondary	Safety and Tolerability as Measured by Number of Participants With Clinically significant Laboratory Abnormalities		Up to Day 29
Secondary	Safety and Tolerability as Measured by Number of Participants With Clinically significant 12-lead ECG Parameters Abnormalities		Up to Day 29
Secondary	Safety and Tolerability as Measured by Number of Participants With Clinically significant Vital Signs Abnormalities		Up to Day 29
Secondary	Safety and Tolerability as Measured by Number of Participants With Clinically significant Physical Examination Abnormalities		Up to Day 29