Hyperion Therapeutics Announces Results of Phase I Study in Patients With Liver...( - Company preparing to initiate phase...),Health

- Company preparing to initiate phase II trial in hepatic encephalopathy -

SOUTH SAN FRANCISCO, Calif., June 2 /PRNewswire/ -- Hyperion Therapeutics, Inc. today announced top-line results from a phase I study of HPN-100 in patients with liver cirrhosis. The data were presented as part of the 2009 Digestive Disease Week meeting. The abstract is titled "Pharmacokinetic (PK) and Safety Analyses of a Novel Ammonia-Reducing Agent in Healthy Adults and Patients with Cirrhosis."

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This open-label study was designed to determine the safety, tolerability, and PK and pharmacodynamic (PD) profiles of HPN-100 administered orally to subjects with hepatic impairment and cirrhosis and to subjects with normal hepatic function. A total of thirty-two subjects were enrolled, including twenty four with cirrhosis (eight each Child-Pugh score A, B, and C), and eight age- and gender-matched healthy subjects with normal hepatic function. Subjects received a single oral dose (100mg/kg/d) of HPN-100 on day 1, two doses of 100mg/kg on each of days 8-14 (total of 200mg/kg/d), and a single dose on day 15 (100mg/kg/d). In order to assess the effects of food on HPN-100 PK, the dose was given fasting on Day 1 and with a meal on Day 8.

HPN-100 was metabolized via the expected major pathway, from phenylbutyrate (PBA) to phenylacetic acid (PAA) and then to phenylacetylglutamine (PAGN). PAGN mediates waste nitrogen excretion and ammonia removal. The extent of plasma exposure to PAA significantly correlated with MELD score (r2= 0.15; p= 0.03), but did not correlate significantly with glomerular filtration rate (r2= 0.01; p= 0.54) or Child-Pugh score (r2= 0.10; p= 0.08). No consistent differences between cirrhotic subjects and healthy volunteers were seen for the plasma PK variables on
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