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

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.