Trial record 6 of 53 for:    MDV3100

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

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:
NCT01901133
First received: June 18, 2013
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Pharmacokinetics of MDV3100
Healthy Subjects
Kidney Diseases
Drug: MDV3100
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase I, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of MDV3100 in Male Subjects With Mild or Moderate Hepatic Impairment and Normal Hepatic Function

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Assessment of pharmacokinetics measured by AUC0-inf following single dose of MDV3100 [ Time Frame: Day 1 through Day 50 (25 times) ] [ Designated as safety issue: No ]
    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.

  • Assessment of pharmacokinetics measured by Cmax following single dose of MDV3100 [ Time Frame: Day 1 through Day 50 (25 times) ] [ Designated as safety issue: No ]
    Maximum concentration (observed) (Cmax) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.


Secondary Outcome Measures:
  • Composite of pharmacokinetics following single dose of MDV3100 [ Time Frame: Day 1 through Day 50 (25 times) ] [ Designated as safety issue: No ]
    Measured by 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), Cmax, t1/2, AUC0-inf, Unbound maximum concentration (observed) (Cmax,u), Unbound AUC extrapolated to infinity (AUC0-inf,u), Unbound apparent total body clearance after extra vascular dosing (CLu/F), Unbound apparent volume of distribution during the terminal phase after extra vascular dosing (Vz,u/F), Fraction unbound (fu).

  • Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG) and clinical safety laboratory and adverse events [ Time Frame: Day 1 through Day 50 ] [ Designated as safety issue: Yes ]
    For hepatic impaired subjects, additional Child-Pugh classification will be performed after MDV3100 administration.


Enrollment: 33
Study Start Date: October 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: Mild hepatic impairment subjects + control Drug: MDV3100
Oral
Other Names:
  • Xtandi
  • enzalutamide
Experimental: B: Moderate hepatic impairment subjects + control Drug: MDV3100
Oral
Other Names:
  • Xtandi
  • enzalutamide

  Eligibility

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

Inclusion Criteria:

  • All subjects must meet all of the following inclusion criteria:

    • 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.
  • Subjects with mild or moderate hepatic impairment must also meet the following inclusion criteria:

    • Child-Pugh classification Class A (mild, 5 or 6 points) or Class B (moderate, 7 to 9 points) liver function impairment.

Exclusion Criteria:

  • 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).
    • Presence of a hepatocellular carcinoma, or an acute liver disease caused by an infection or drug toxicity.
    • Severe portal hypertension or surgical porto-systemic shunts, including TIPSS (Transjugular intrahepatic portosystemic shunt).
    • Biliary obstruction or other cause of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
    • Signs of significant hepatic encephalopathy (Hepatic encephalopathy score >2).
    • Severe ascites and/or pleural effusion
    • Esophageal variceal bleeding in the medical history.
    • Thrombocyte level below 40x109/L and /or hemoglobin below 90 g/L.
    • Previous liver transplantation.
    • Positive serology test for, anti HAV (IgM), anti-HIV-1 or anti-HIV-2.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01901133

Locations
Moldova, Republic of
Arensia
Chisinau, Moldova, Republic of
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Medivation, Inc.
Investigators
Study Chair: Operation Senior Research Manager Astellas Pharma Europe B.V.
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01901133     History of Changes
Other Study ID Numbers: 9785-CL-0009
Study First Received: June 18, 2013
Last Updated: July 15, 2013
Health Authority: Moldova: Ministry of Health

Keywords provided by Astellas Pharma Inc:
Phase 1
MDV3100
Hepatic Impairment
Kidney Diseases
Xtandi
enzalutamide

Additional relevant MeSH terms:
Kidney Diseases
Liver Diseases
Urologic Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 17, 2014