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
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Debiopharm International SA
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Mass Balance Recovery Measured Through Total Radioactivity Excreted in Expired Air, Urine and Feces
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- Male
- Accepts 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.
Arms & Interventions
Radiolabeled Xevinapant Oral Solution
Participants will receive:
• single oral dose of [14C]-xevinapant, as an oral solution
Intervention: Radiolabelled Xevinapant 200 mg (Oral Solution) (Drug)
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
Intervention: Radiolabelled Xevinapant 100 μg (IV Solution) (Drug)
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
Intervention: Xevinapant 200 mg (Oral Solution) (Drug)
Outcomes
Primary Outcomes
Mass Balance Recovery Measured Through Total Radioactivity Excreted in Expired Air, Urine and Feces
Time Frame: 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
Time Frame: 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
Time Frame: Up to Day 29
Maximum Observed Concentration (Cmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
Time Frame: 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
Time Frame: Up to Day 29
Absolute Bioavailability (F) of Xevinapant in Plasma
Time Frame: Up to Day 5
Absolute Bioavailability (F) = (AUC0-infinity \[oral\]/ dose \[oral\]) /(AUC0-infinity \[IV\]/ dose \[IV\])
Time to Maximum Observed Concentration (Tmax) of Total Radioactivity in Blood and Plasma, and of Xevinapant and Metabolite in Plasma
Time Frame: Up to Day 29
Apparent Total Clearance (CL/F) of Total Radioactivity in Blood and Plasma and of Xevinapant and Metabolite in Plasma
Time Frame: Up to Day 29
Renal Clearance (CLr) of Total Radioactivity, Xevinapant and Metabolite
Time Frame: Up to Day 29
Xevinapant Metabolite Concentrations in Urine, Feces, Blood and Plasma
Time Frame: Up to Day 8
Secondary Outcomes
- 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)
- 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 Physical Examination Abnormalities(Up to Day 29)
- Blood to Plasma Ratio of Xevinapant and Metabolite(Up to Day 8)