Methods of treating hepatic encephalopathy
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Publication Number
US-10709694-B2
Publication Date
2020-07-14
Expiration Date
Abstract
The application describes treatment of hepatic encephalopathy using gastrointestinal specific antibiotics. One example of a gastrointestinal specific antibiotic is rifaximin.
Core Innovation
The invention relates to a method of reducing a subject's risk of experiencing a breakthrough overt hepatic encephalopathy (HE) episode. The method comprises administering rifaximin daily to the subject for about 6 months or longer, in an amount between about 1000 mg and about 1200 mg.
The document describes hepatic encephalopathy as linked to gut-derived nitrogenous toxins and ammonia, and describes rifaximin as a gastrointestinal (GI)-specific antibiotic with negligible systemic absorption and gut-focused activity. This supports reducing risk of breakthrough overt HE by targeting the gut source.
The document describes breakthrough overt HE using Conn (West Haven) score, including Conn score grade thresholds and optionally asterixis grade. Multiple efficacy endpoints are described, including increased time to breakthrough HE, reduced risk of HE-related and HE-caused hospitalizations, improved or maintained Conn scores and asterixis grades, reductions in venous ammonia concentration, and improvements in critical flicker frequency (CFF).
Claims Coverage
The partial content includes one independent claim. It covers a daily rifaximin regimen of about 1000 mg to about 1200 mg administered for about 6 months or longer to reduce the risk of breakthrough overt hepatic encephalopathy (HE) episodes, with dependent claim refinements that add specific dosing schedules and characterize breakthrough overt HE using Conn (West Haven) criteria.
Reducing risk of breakthrough overt hepatic encephalopathy with daily rifaximin
A method of reducing a subject's risk of experiencing a breakthrough overt hepatic encephalopathy (HE) episode by administering to the subject between about 1000 mg to about 1200 mg of rifaximin daily for a period of about 6 months or longer.
Administering rifaximin at 1100 mg per day
A method wherein 1100 mg of rifaximin is administered each day.
Administering rifaximin at 550 mg twice daily
A method wherein 550 mg of rifaximin is administered twice daily.
Defining breakthrough overt HE by Conn score grade threshold
A method wherein a breakthrough overt HE episode is characterized by an increase in the Conn score to a grade of at least 2.
Selecting subjects by MELD score range
A method performed for a subject whose Model for End-Stage Liver Disease (MELD) score is between 1 and 24.
Optional administration of lactulose
A method further comprises administering lactulose.
Across the claim set shown, coverage centers on administering rifaximin within about 1000–1200 mg/day for about 6 months or longer to reduce the risk of breakthrough overt HE, with dependent claim limitations specifying particular daily or twice-daily rifaximin dosing, Conn (West Haven) score-based characterization of breakthrough overt HE, eligibility by MELD score range, and optional lactulose combination.
Stated Advantages
Reduces a subject's risk of experiencing a breakthrough overt hepatic encephalopathy (HE) episode.
Increases time to breakthrough HE.
Reduces the risk of HE-related hospitalizations and HE-caused hospitalizations.
Improves or maintains Conn scores and asterixis grades.
Reduces venous ammonia concentration.
Improves critical flicker frequency (CFF).
Rifaximin is described as having negligible systemic absorption with gut-focused activity.
Documented Applications
Preventing breakthrough overt hepatic encephalopathy (HE) episodes in subjects, using rifaximin administered daily for about 6 months or longer.
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