A Study to Assess the Pharmacokinetics of the Hydrocodone Extended-Release Tablet (CEP-33237) in Subjects With Normal Renal Function and Subjects With Varying Degrees of Renal Impairment

This is a multicenter, open-label, parallel-group pharmacokinetic and safety study to assess
the effect of varying degrees of renal impairment (mild, moderate, severe and end stage
renal disease [ESRD])on the pharmacokinetics of the hydrocodone bitartrate extended-release
tablet at a single dose of 45 mg as compared with subjects with normal renal function. The
study consists of a screening visit within 21 days before study drug administration (visit
1), followed by a single-dose administration period including a 144-hour pharmacokinetic
sampling period (visit 2) with a final assessment after the final pharmacokinetic sample is
collected or upon early withdrawal, and a follow-up visit 48 to 72 hours after the last
discharge from the study center (visit 3). Subjects will be categorized into either the
control group with normal renal function or one of the four groups of subjects with varying
degrees of renal impairment. Up to 12 subjects in each of the 5 groups will be enrolled
with the intent that a minimum of 8 subjects in each group will complete the study.

Eligible subjects will check in to the study center on day -1. Subjects who continue to
meet the criteria for enrollment will receive a single dose of the hydrocodone bitartrate
extended-release tablet on day 1. Subjects will receive one 50-mg tablet of naltrexone
hydrochloride to block opioid receptors and minimize opioid related adverse events
approximately 15 and 3 hours before and approximately 9 and 21 hours after study drug
administration. Blood and urine samples will be collected just before study drug
administration and over a 144-hour period after study drug administration. Safety will be
assessed throughout the study by monitoring the occurrence of adverse events, clinical
laboratory test results, vital signs measurements,12-lead ECG findings, physical examination
findings, SpO2 findings, and use of concomitant medications. Subjects who complete all
scheduled visits will have final procedures and assessments performed prior to discharge
from the study center after pharmacokinetic sampling is complete. All subjects will be
asked to return for a follow-up visit.