Ocera Therapeutics Completes Phase 2B Enrollment in the ASTUTE Trial

SAN DIEGO, Feb. 23 /PRNewswire/ -- Ocera Therapeutics, Inc. announced today that the ASTUTE Study (AST-120 Used to Treat Hepatic Encephalopathy) has completed enrollment for its Phase 2B study ahead of schedule, with data expected mid 2010.

AST-120 adsorbs ammonia and other gut derived toxins that factor prominently in the underlying cause of mild hepatic encephalopathy (MHE), a neurocognitive disorder present in a majority of patients with cirrhosis of the liver. Because MHE leads to a change in cognitive function including personality changes and intellectual impairment, the disorder has a profound negative impact on quality of life. MHE patients are at increased risk of motor vehicle accidents, losing their job and eventually hospitalization due to acute hepatic encephalopathy.

"This first study of MHE enrolled ahead of schedule and established prospectively that a majority of patients with otherwise stable cirrhosis suffer from MHE - which speaks to the pent-up demand for a safe and well tolerated treatment option for MHE patients.  The Phase 2B study is the first to use a more sensitive and validated assessment instead of the West Haven Conn criteria which has been deemed unreliable in this population," stated Laurent Fischer, M.D., CEO of Ocera Therapeutics. "There is a great unmet medical need to routinely diagnose and offer a safe and well tolerated treatment option for the majority of the people with liver cirrhosis who have MHE but are not aware of the specific disorder."

"The importance of MHE has, until recently, been under appreciated, but this landmark study, shows that we can no longer ignore MHE.  The scope of the problem is simply too big to avoid and we should consider screening all patients with severe liver disease for neurocognitive deficits," said Dr. Kevin Mullen, Consultant Hepatologist and Professor of Medicine at Case Western Reserve University. "AST-120 is a potentially attractive treatment option for MHE because of its well established safety profile, which appears similar to placebo, and its lack of known interaction with other drugs."

The study is a randomized, double blind, multicenter study which enrolled 150 patients with MHE. The study employed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to screen and evaluate cirrhotic patients for evidence of MHE, and found that MHE was present in over half of patients screened. Subjects were randomly assigned to receive either AST-120 or placebo for up to eight weeks. The study was designed to evaluate the effects of AST-120 on neurocognitive function using a variety of validated instruments. In addition, quality of life, clinical global evaluations and safety assessments will be conducted.  

About AST-120

AST-120 (spherical carbon adsorbent) is a novel proprietary adsorbent with selective adsorption for a variety of unwanted substances and toxins, most importantly ammonia, the lead toxin responsible for hepatic encephalopathy in patients with liver cirrhosis. Preclinical studies show that AST-120 lowers ammonia and reduces brain swelling in a model of cirrhosis.  A Phase 2 study presented at EASL 2009 showed that AST-120 improved West Haven score and complex computation and was better tolerated than lactulose. In addition, only AST-120 reduced bile acid levels and itching associated with liver cirrhosis. AST-120 also adsorbs other substances, which may be responsible for conditions including Irritable Bowel Syndrome. Adsorbed substances include ammonia, serotonin, histamine, advanced glycation endproducts, and bacterial toxins. Ocera Therapeutics licensed AST-120 from Kureha (Japan) in 2005.  AST-120 has been used chronically by over 360,000 patients in Japan where the drug is marketed and studied in over 3,000 patients worldwide.

About Hepatic Encephalopathy and Liver Cirrhosis

About one million people in the United States have liver cirrhosis as a result of chronic Hepatitis C, alcohol abuse and NASH, a complication of obesity. Hepatic Encephalopathy (HE) is a neuropsychiatric condition in which severe liver disease contributes to an accumulation of toxic substances, including ammonia that impair brain function. HE ranges in severity from mild personality changes to disorientation, delirium, coma and death. It has been reported that up to 80 percent of patients with cirrhosis of the liver who do not have evidence of overt HE will still have neuropsychiatric impairment if tested using an instrument such as the RBANS. This more subtle impairment previously known as minimal or subclinical HE has been termed Mild HE, and is associated with impaired quality of life, job loss and increased risk of motor vehicle accident. For the last 30 years, lactulose, a non-absorbed disaccharide, has been the standard of care for the treatment of Acute HE but is poorly tolerated due to its side effects including diarrhea and bloating.  Patients with liver cirrhosis are currently rarely diagnosed with Mild HE and the current West Haven Conn score is unreliable for patients with mild forms of the disease.  Guidelines issued in 2009 recommend to use validated neurocognitive tools to diagnose MHE, a condition for which there is no approved treatment.

About Ocera Therapeutics, Inc.

Based in San Diego, CA, and privately held, Ocera is focused on the development of proprietary treatments for acute and chronic liver diseases and gastrointestinal disorders. Ocera is also developing OCR-002, an ammonia detoxification agent, for the treatment of hospitalized patients with acute hepatic encephalopathy and acute liver failure. Ocera raised $62 million dollars in venture financing from Domain Associates, Sofinnova Ventures, Thomas, McNerney & Partners, Montagu Newhall and InterWest Partners. Additional information can be found at www.oceratherapeutics.com.

SOURCE Ocera Therapeutics, Inc.