Liver disease
Inventors
Patel, Mahesh V. • Chidambaram, Nachiappan • Nachaegari, Satish K. • Byrne, Burke • Kim, Kilyoung • Baker, Jonathan A.
Assignees
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Publication Number
US-12150945-B2
Publication Date
2024-11-26
Expiration Date
Abstract
Methods of treating a liver disease or condition, or a symptom thereof, in a subject in need of treatment, are disclosed and described. One method comprises orally administering to a subject, a pharmaceutical composition having an amount of a testosterone, or an ester thereof, sufficient to treat the liver disease or condition, or symptom thereof.
Core Innovation
The invention relates to oral testosterone-ester pharmaceutical compositions for treating a fatty liver condition in a subject having hepatocellular ballooning. The pharmaceutical composition includes a testosterone ester component (TEC) consisting essentially of testosterone dodecanoate (TD), and in response to oral administration hepatocellular ballooning is resolved by a reduction of hepatocellular ballooning by at least one NAS point. The disclosed treatment is also linked to resolution of at least one of NASH, NASH with cirrhosis, and NAFLD.
The disclosed method applies sex-specific TEC dosing, with TEC provided at about 200 mg to about 750 mg when the subject is male and at about 1/10th to about 1/15th of about 200 mg to about 750 mg when the subject is female. Resolution is determined by histopathological interpretation and includes endpoints such as a hepatocellular ballooning score of zero and an inflammation score of no more than one. Additional embodiments define resolution by a reduction in liver fat, a reduction in inflammation, and no worsening of fibrosis.
The document further describes oral testosterone-ester formulations and excipient/carrier compositions for soft gel capsules and hard gel capsules, including hydrophilic additives, solubilizers, surfactants, polymers, antioxidants, glycerides, and fatty acids. It also includes associated clinical trial and study reporting for oral testosterone-ester approaches, with reported outcomes including MRI-PDFF liver fat reductions, NAFLD/NASH resolution-related results, and biomarker and laboratory parameter changes.
Claims Coverage
The provided claim set identifies four independent claims. Across these claims, the inventive features center on oral administration of a TD-containing testosterone ester component with sex-specific dosing and histopathology-defined resolution of fatty liver conditions, including hepatocellular ballooning and related endpoints.
Oral testosterone dodecanoate testosterone ester component to resolve hepatocellular ballooning
Orally administering a pharmaceutical composition to a subject having hepatocellular ballooning, where the pharmaceutical composition includes a testosterone ester component (TEC) consisting essentially of testosterone dodecanoate (TD), and wherein in response to the administration hepatocellular ballooning is resolved by a reduction of hepatocellular ballooning by at least one NAS point.
Sex-specific TD dosing for resolution confirmed by histopathological interpretation
Orally administering the pharmaceutical composition to a subject having at least one of NASH, NASH with cirrhosis, and NAFLD, where the composition includes a TEC consisting essentially of TD administered at about 200 mg to about 750 mg when the subject is male and at about 1/10th to about 1/15th of about 200 mg to about 750 mg when the subject is female, and wherein resolution is confirmed by histopathological interpretation indicating a hepatocellular ballooning score of zero and an inflammation score of no more than one.
Resolution defined by multiple liver-fat, ballooning, inflammation, and fibrosis-worsening endpoints
Orally administering a pharmaceutical composition to a subject having at least one of NASH, NASH with cirrhosis, and NAFLD, where the composition includes a TEC consisting essentially of TD administered at about 200 mg to about 750 mg when the subject is male and at about 1/10th to about 1/15th of about 200 mg to about 750 mg when the subject is female, and wherein resolution comprises at least one of a reduction in liver fat, a reduction in hepatocellular ballooning, a reduction in inflammation, and no worsening of fibrosis.
Hepatocellular ballooning reduction combined with liver fat and inflammation improvement without fibrosis worsening
Orally administering a pharmaceutical composition to a subject having at least one of NASH, NASH with cirrhosis, and NAFLD, where the composition includes a TEC consisting essentially of TD administered at about 200 mg to about 750 mg when the subject is male and at about 1/10th to about 1/15th of about 200 mg to about 750 mg when the subject is female, and wherein resolution comprises a reduction in hepatocellular ballooning and at least one of a reduction in liver fat, a reduction in inflammation, and no worsening of fibrosis.
Across the independent claims, the coverage centers on oral administration of a TD-containing testosterone ester component with sex-specific dosing and resolution of fatty liver conditions. Resolution is supported by histopathological interpretation endpoints and/or by improvement definitions spanning hepatocellular ballooning, liver fat, inflammation, and no worsening of fibrosis.
Stated Advantages
Resolves hepatocellular ballooning as shown by a reduction of hepatocellular ballooning by at least one NAS point.
Resolves at least one of NASH, NASH with cirrhosis, and NAFLD.
Resolves NASH/NAFLD with histopathological confirmation including a hepatocellular ballooning score of zero and an inflammation score of no more than one.
Provides resolution that includes reductions in liver fat and inflammation and avoids worsening of fibrosis.
Documented Applications
Treating a fatty liver condition by orally administering a testosterone ester component consisting essentially of testosterone dodecanoate to resolve hepatocellular ballooning in subjects.
Treating fatty liver conditions including NASH, NASH with cirrhosis, and NAFLD by oral administration of a TEC consisting essentially of TD, with resolution confirmed histopathologically.
Clinical trial evaluation of oral testosterone therapy (example clinical trial described).
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