Hepatic Impairment Study With MDV3100 in Subjects With Mild and Moderate Hepatic Impairment Compared to a Healthy Control Group

NCT01901133 | Completed Phase 1

• 1 other identifier: 9785-CL-0009
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the influence of hepatic impairment on the pharmacokinetics, safety and tolerability of a single dose of MDV3100 in male subjects. The study will consist of two treatment arms. Arm A will assess the influence of mild hepatic impairment, and Arm B will assess the influence of moderate hepatic impairment. Data obtained from subjects with hepatic impairment will be compared to data from Body Mass Index (BMI) and age-matched subjects with normal hepatic function.

Conditions

Pharmacokinetics of MDV3100; Healthy Subjects; Kidney Diseases

Keywords

Phase 1; MDV3100; Hepatic Impairment; Kidney Diseases; Xtandi; enzalutamide

Outcome Measures

Primary Outcomes (2)

• Assessment of pharmacokinetics measured by AUC0-inf following single dose of MDV3100

  Area under the plasma concentration - time curve extrapolated to infinity (AUC0-inf) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.

  Day 1 through Day 50 (25 times)

• Assessment of pharmacokinetics measured by Cmax following single dose of MDV3100

  Maximum concentration (observed) (Cmax) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.

  Day 1 through Day 50 (25 times)

Secondary Outcomes (2)

• Composite of pharmacokinetics following single dose of MDV3100

  Day 1 through Day 50 (25 times)

• Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG) and clinical safety laboratory and adverse events

  Day 1 through Day 50

Study Arms (2)

A: Mild hepatic impairment subjects + control

EXPERIMENTAL

Drug: MDV3100

B: Moderate hepatic impairment subjects + control

EXPERIMENTAL

Drug: MDV3100

Interventions

MDV3100 DRUG

Oral

Also known as: Xtandi, enzalutamide

A: Mild hepatic impairment subjects + control; B: Moderate hepatic impairment subjects + control

Eligibility Criteria

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

You may qualify if:

• Subject must be non-fertile, i.e., surgically sterilized or must practice an adequate contraceptive method to prevent pregnancies
• Body Mass Index (BMI) of at least 18.5 and no greater than 34.0 kg/m2.
• Child-Pugh classification Class A (mild, 5 or 6 points) or Class B (moderate, 7 to 9 points) liver function impairment.

You may not qualify if:

• All subjects must not have any of the following characteristics:
• Known or suspected hypersensitivity to MDV3100 or any components of the formulation used.
• 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).
• Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active hay fever).
• Abnormal pulse and/or blood pressure (BP) measurements at the pre-study visit as follows: Pulse \<40 or \>90 bpm; mean systolic BP \>160 mmHg; mean diastolic BP \>100 mmHg (BP measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured
• A QTcF interval of \>450 ms after repeated measurements (consistently after duplicate measurements), a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).
• Significant renal dysfunction (creatinine clearance below 60 mL/min, estimated according to the method of modification of diet in renal disease (MDRD) formula).
• Regular use of any inducer of metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.
• Participation in any clinical study within 3 months or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study, provided that the clinical study did not entail a biological compound with a long terminal half life.
• For subjects with normal hepatic function:
• Regular use of any prescribed or OTC (over-the-counter) drugs, which includes vitamins, natural and herbal remedies (e.g. St John's wort) and food supplements in the 4 weeks prior to admission to the Clinical Unit and use of any drugs in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day).
• Positive serology test for HBsAg, anti HAV (IgM), anti-HCV, anti-HIV-1 or anti-HIV-2.
• For subjects with mild or moderate hepatic impairment:
• 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. (e.g. advanced ascites, infection of ascites, fever, active gastrointestinal bleeding).
• Change in dose regimen of medically required medication within the last two weeks before pre-study examination (allowed co-medication in patients), and/or the use of unallowed co-medication in the 3 weeks prior to admission to the clinical unit (not allowed: any known hepatic enzyme altering agents or compounds known to restrict metabolism).

Sponsors & Collaborators

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

Study Sites (1)

Arensia

Chisinau, Moldova

Location

Related Publications (1)

• Gibbons JA, Ouatas T, Krauwinkel W, Ohtsu Y, van der Walt JS, Beddo V, de Vries M, Mordenti J. Clinical Pharmacokinetic Studies of Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1043-55. doi: 10.1007/s40262-015-0271-5.

  PMID: 25917876 DERIVED

MeSH Terms

Conditions

Kidney Diseases

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Operation Senior Research Manager

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 18, 2013
• First Posted: July 17, 2013
• Study Start: October 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: September 15, 2014

Record last verified: 2014-09

Locations

MO (1)