A Study to Investigate the Effect of Severely Diminished Liver Function on the Metabolism, Safety, and Tolerability of a Single Oral Dose of Enzalutamide in Men

NCT02138162 | Completed Phase 1

• 2 other identifiers: 9785-CL-04042012-004858-29
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The influence of severely diminished liver function on the metabolism, safety, and tolerability of a single oral dose of enzalutamide in a group of 8 men. The results are compared to the data gained from 8 age- and BMI-matched men with normal liver function.

Conditions

Severe Hepatic Impairment; Normal Hepatic Function

Keywords

Phase 1; Pharmacokinetics; Safety; Severe hepatic impairment; Enzalutamide

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics (PK) of enzalutamide after a single oral dose

  area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)

  Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50

• PK of enzalutamide after a single oral dose

  maximum concentration (observed) (Cmax)

  Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50

• PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose

  area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)

  Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50

• PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose

  maximum concentration (observed) (Cmax)

  Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50

Secondary Outcomes (2)

• PK of enzalutamide, M1, M2 and the sum of enzalutamide plus N-desmethyl enzalutamide (M2)

  Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50

• Additional pharmacokinetic variables for enzalutamide, and, as appropriate, for M1 and M2, based upon unbound plasma concentrations

  Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50

Study Arms (2)

1:Single dose of enzalutamide in hepatically impaired subjects

EXPERIMENTAL

Single dose of enzalutamide

Drug: enzalutamide

2:Single dose of enzalutamide in healthy subjects

EXPERIMENTAL

Single dose of enzalutamide

Drug: enzalutamide

Interventions

enzalutamide DRUG

oral

Also known as: ASP9785,, MDV3100,, Xtandi

1:Single dose of enzalutamide in hepatically impaired subjects; 2:Single dose of enzalutamide in healthy subjects

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.
• Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.
• Subject has a Body Mass Index (BMI) range of 18.5 - 34.0 kg/m2 inclusive. The subject weighs at least 50 kg \[at Screening\].
• Subject has a Child-Pugh classification Class C (severe, 10 to 15 points).
• Age- and BMI-matched to subjects with severe liver hepatic impairment.

You may not qualify if:

• Subject has known or suspected hypersensitivity to enzalutamide, or any components of the formulation used.
• Subject has history of seizure or any condition that may predispose to seizure. Also history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit).
• Subject has used grapefruit (or grapefruit containing products) or marmalade in the week prior to admission to the clinical unit (Day -1), as reported by the subject.
• Subject has any of the liver function tests above the upper limit of normal.
• Subject has fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period.
• Subject has surgical porto-systemic shunts, including TIPSS (Trans-jugular intrahepatic portosystemic shunt).
• Subject has presence of severe hepatic encephalopathy (grade \> 2).
• Subject has advanced ascites.
• Subject has esophageal variceal bleeding in the medical history (within 6 months before Day -1).
• Subject has thrombocyte level below 40x109 /L and /or hemoglobin below 90 g/L.
• Subject has significant renal dysfunction (creatinine clearance below 50 mL/min, estimated according to the method of Modification of Diet in Renal Disease (MDRD) formula).
• Subject has had previous liver transplantation.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead
• Medivation, Inc.: collaborator

Study Sites (1)

Comac Medical Ltd.

Sofia, 1612, Bulgaria

Location

MeSH Terms

Interventions

enzalutamide

Study Officials

• Medical Monitor

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

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: May 12, 2014
• First Posted: May 14, 2014
• Study Start: August 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 14, 2014

Record last verified: 2014-05

Locations

BU (1)