Trial record 5 of 79 for:    Enzalutamide

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

This study has been completed.
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT02138162
First received: May 12, 2014
Last updated: NA
Last verified: May 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Severe Hepatic Impairment
Normal Hepatic Function
Drug: enzalutamide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase 1, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of Enzalutamide in Male Subjects With Severe Hepatic Impairment and Normal Hepatic Function

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetics (PK) of enzalutamide after a single oral dose [ Time Frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50 ] [ Designated as safety issue: No ]
    area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)

  • PK of enzalutamide after a single oral dose [ Time Frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50 ] [ Designated as safety issue: No ]
    maximum concentration (observed) (Cmax)

  • PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose [ Time Frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50 ] [ Designated as safety issue: No ]
    area under the plasma concentration - time curve (AUC) extrapolated to infinity (AUC0-inf)

  • PK of enzalutamide plus N-desmethyl enzalutamide (M2) after a single oral dose [ Time Frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50 ] [ Designated as safety issue: No ]
    maximum concentration (observed) (Cmax)


Secondary Outcome Measures:
  • PK of enzalutamide, M1, M2 and the sum of enzalutamide plus N-desmethyl enzalutamide (M2) [ Time Frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50 ] [ Designated as safety issue: No ]
    Cmax and AUC0-inf (M1, M2 only), time to attain Cmax (tmax), AUC up to last quantifiable concentration (AUC0-last), apparent terminal elimination half life (t1/2), apparent volume of distribution during the terminal phase after extra vascular dosing (Vz/F), apparent total body clearance after extra vascular dosing (CL/F) (parent compound only), Metabolite-to-Parent Ratio (MPR), percent extrapolated for AUC0-inf (%AUC)

  • Additional pharmacokinetic variables for enzalutamide, and, as appropriate, for M1 and M2, based upon unbound plasma concentrations [ Time Frame: Days 1-6, 8, 12, 15, 19, 22, 26, 29, 36, 43, 50 ] [ Designated as safety issue: No ]
    Unbound Cmax (Cmax,u), unbound AUC0-inf (AUC0-inf,u), and unbound AUC0-last (AUC0-last,u). Unbound CL/F (CLu/F) and unbound Vz/F (Vz,u/F) (parent only)


Enrollment: 16
Study Start Date: August 2013
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1:Single dose of enzalutamide in hepatically impaired subjects
Single dose of enzalutamide
Drug: enzalutamide
oral
Other Names:
  • ASP9785,
  • MDV3100,
  • Xtandi
Experimental: 2:Single dose of enzalutamide in healthy subjects
Single dose of enzalutamide
Drug: enzalutamide
oral
Other Names:
  • ASP9785,
  • MDV3100,
  • Xtandi

Detailed Description:

Screening takes place between Day -22 and Day -2, and subjects are admitted to the clinic on Day -1. Each subject receives a single oral dose of enzalutamide on Day 1, under fasted conditions. They are discharged on Day 7; ambulant visits take place until Day 50. An End of Study Visit (ESV) occurs 7-10 days after the last PK sampling or early withdrawal.

Full PK profiles are obtained for enzalutamide, metabolite 1 of enzalutamide (M1) and metabolite 2 of enzalutamide (M2) up to 1176 hours (Day 50) after administration.

Safety assessments are performed throughout the study. For subjects with severe hepatic impairment, additional Child-Pugh classification and laboratory safety tests (including liver function tests) are performed regularly after administration.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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].

Inclusion Criteria:Subjects with severe hepatic impairment must also meet the following inclusion criteria:

  • Subject has a Child-Pugh classification Class C (severe, 10 to 15 points).

Inclusion Criteria: For Healthy Subjects Only:

  • Age- and BMI-matched to subjects with severe liver hepatic impairment.

Exclusion Criteria:

  • 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.

Exclusion Criteria: For Healthy Subjects Only:

  • Subject has any of the liver function tests above the upper limit of normal.

Exclusion Criteria: Subjects with severe hepatic impairment must also not have any of the following characteristics:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02138162

Locations
Bulgaria
Comac Medical Ltd.
Sofia, Bulgaria, 1612
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Medivation, Inc.
Investigators
Study Director: Medical Monitor Astellas Pharma Europe B.V.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT02138162     History of Changes
Other Study ID Numbers: 9785-CL-0404, 2012-004858-29
Study First Received: May 12, 2014
Last Updated: May 12, 2014
Health Authority: Bulgaria: Bulgarian Drug Agency
United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Phase 1
Pharmacokinetics
Safety
Severe hepatic impairment
Enzalutamide

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on October 22, 2014