TMC435-TiDP16-C113: A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics of TMC435

This is a Phase I, open-label trial to investigate the pharmacokinetics (how the drug is
absorbed into the bloodstream, distributed in the body and eliminated from the body) of
TMC435 in 8 participants with moderate hepatic impairment and 8 participants with severe
hepatic impairment as compared to 8 participants with normal hepatic function, matched for
age, gender, race, BMI (body mass index = weight in kilogram divided by square of height in
meters) and smoking status. Open-label means that the study doctor and the participants know
what treatment will be assigned to them. All participants will receive 150 mg of TMC435 by
mouth for 7 days. Participants with severe hepatic impairment will be treated when the
pharmacokinetic profiles of TMC435 in participants with moderate hepatic impairment have
been evaluated. The dose of TMC435 may be changed for participants with severe hepatic
impairment after evaluation of the blood levels TMC435 in participants with moderately
impaired hepatic function. Tolerability and safety of TMC435 will be assessed throughout the
trial period. Illnesses and side effects will be checked at every visit. Blood samples will
be taken at screening, on the day before TMC435 intake, on days 2, 3, 5, 6, 7 (11 times), 8
and 9 and at 2 follow-up visits. Blood levels of TMC435 will be determined on days 2, 5, 6,
7, 8 and 9. Urine samples, ECG and vital signs will be taken at screening, twice on day 7
and at 2 follow-up visits. A physical examination will be done at screening, on the day
before TMC435 intake, on day 9 and at both follow-up visits. All participants will receive a
150 mg dose of TMC435 for 7 days, given by mouth as 2 capsules of 75 mg. After evaluation of
the pharmacokinetic profiles of TMC435 in participants with moderate hepatic impairment, the
dose may be changed for participants with severe hepatic impairment.