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

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Astellas Pharma Europe B.V.
• Collaborator: Medivation, Inc.

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.