hepatic impairment study with mdv3100 in subjects with mild and moderate hepatic impairment compared to a healthy control group

Conditions: Pharmacokinetics of MDV3100; Healthy Subjects; Kidney Diseases

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.


Eligibility 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 \ 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.

Keywords: phase 1 mdv3100 hepatic impairment kidney diseases xtandi enzalutamide