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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01901133
• Other study ID #: 9785-CL-0009
• Status: Completed
• Phase: Phase 1
• First received: June 18, 2013
• Last updated: September 12, 2014
• Start date: October 2011
• Est. completion date: January 2012

Study information

• Verified date: September 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: Moldova: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 69 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Subjects
• Kidney Diseases
• Liver Diseases
• Pharmacokinetics of MDV3100

Intervention

Drug:
• MDV3100
Oral

Locations

Country	Name	City	State
Moldova, Republic of	Arensia	Chisinau

Sponsors (2)

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

Country where clinical trial is conducted

Moldova, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of pharmacokinetics measured by AUC0-inf following single dose of MDV3100	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.	Day 1 through Day 50 (25 times)	No
Primary	Assessment of pharmacokinetics measured by Cmax following single dose of MDV3100	Maximum concentration (observed) (Cmax) in subjects with mild and moderate hepatic impairment to matched control subjects with normal hepatic function.	Day 1 through Day 50 (25 times)	No
Secondary	Composite of pharmacokinetics following single dose of MDV3100	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).	Day 1 through Day 50 (25 times)	No
Secondary	Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG) and clinical safety laboratory and adverse events	For hepatic impaired subjects, additional Child-Pugh classification will be performed after MDV3100 administration.	Day 1 through Day 50	Yes

External Links

•   Link to Results on JAPIC - enter 140591 in the JapicCTI-RNo. field