Status:

COMPLETED

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

Lead Sponsor:

Astellas Pharma Europe B.V.

Collaborating Sponsors:

Medivation, Inc.

Conditions:

Pharmacokinetics of MDV3100

Healthy Subjects

Eligibility:

MALE

18-69 years

Phase:

PHASE1

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....

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

October 1 2011

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 1 2012

Estimated Enrollment :

33 Patients enrolled

Trial Details

Trial ID

NCT01901133

Start Date

October 1 2011

End Date

January 1 2012

Last Update

September 15 2014

Active Locations (1)

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Arensia

Chisinau, Moldova