Composition and method for oral delivery of androgen prodrugs
Inventors
Patel, Mahesh V. • Chidambaram, Nachiappan • Nachaegari, Satish K.
Assignees
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Publication Number
US-12310978-B2
Publication Date
2025-05-27
Expiration Date
Abstract
Provided oral testosterone undecanoate compositions can be administered to hypogonadal males with a meal without the fat content of the meal substantially effecting bioavailability.
Core Innovation
The disclosure provides oral testosterone undecanoate pharmaceutical compositions for replacement therapy in a male having a condition associated with a deficiency or absence of endogenous testosterone. The method orally administers testosterone undecanoate with a meal that includes a predetermined amount of fat, or includes meals containing at least one of standard fat, low fat, and high fat. The administration provides bioequivalent amounts of serum testosterone and related analyte levels, including testosterone undecanoate, dihydrotestosterone, or dihydrotestosterone undecanoate levels.
The disclosure frames the performance requirement as maintenance of bioequivalence across meal fat conditions, including equivalence of serum testosterone pharmacokinetic measures. The described measures include serum testosterone and metabolite-related comparisons such as Cmax and Cavg, as well as AUC(0-t) and AUC(0-infinity). Meal-fat impact is addressed by conducting comparisons across fasted and fed conditions and by defining meal conditions using meal fat content or weight-percent fat ranges.
The compositions are further characterized by formulation components and pharmaceutically acceptable carriers, including both a lipophilic additive and a hydrophilic additive. Example formulation exemplars are described, including Maisine 35-1 (glyceryl monolinoleate), Cremophor RH 40 (polyoxyl 40 hydrogenated castor oil), and PEG 8000. The disclosure also provides oral unit dosage forms and meal-associated labeling concepts, tied to ensuring bioequivalent serum testosterone-related levels across fat-containing meals.
Claims Coverage
The independent claims cover meal-associated oral testosterone undecanoate replacement therapy and require bioequivalent serum testosterone-related levels across meal fat conditions, with specified ranges and additional constraints. Across the independent claims, the main inventive features total 4 core concepts.
Meal-associated oral testosterone undecanoate bioequivalence across fat content
Orally administering to a male having a condition associated with a deficiency or absence of endogenous testosterone, with a meal having a fat content of a predetermined amount, a pharmaceutical composition comprising testosterone undecanoate and a pharmaceutically acceptable carrier, wherein the composition provides bioequivalent amounts of serum testosterone, testosterone undecanoate, dihydrotestosterone, or dihydrotestosterone undecanoate levels regardless of the amount or wt % fat of the meal.
Serum testosterone Cavg range with twice-a-day administration
Providing a serum testosterone Cavg in the range of 300 ng/dl to 1100 ng/dL and administering the method twice-a-day.
Daily testosterone undecanoate amount and unit dosage forms per day
Administering a daily amount of testosterone undecanoate and administering the pharmaceutical composition as multiple unit dosage forms per day.
Lipophilic and hydrophilic additive formulation
Providing a pharmaceutical composition that comprises a lipophilic additive and a hydrophilic additive.
Collectively, the independent claims require meal-associated oral dosing of testosterone undecanoate for replacement therapy such that serum testosterone-related analyte levels are bioequivalent across meal fat conditions, while also specifying a serum testosterone Cavg range, twice-a-day dosing, and a formulation that includes both a lipophilic additive and a hydrophilic additive.
Stated Advantages
Bioequivalent amounts of serum testosterone and related analyte levels are provided regardless of the amount or wt % fat of the meal.
Maintains a serum testosterone Cavg in the range of 300 ng/dL to 1100 ng/dL when administered twice-a-day.
Documented Applications
Replacement therapy in a male for a condition associated with a deficiency or absence of endogenous testosterone using oral administration of testosterone undecanoate with a meal containing fat.
Use of meal-associated labeling concepts such as “WITH A MEAL” and “NOT ON EMPTY STOMACH” tied to bioequivalent serum testosterone-related levels across fat-containing meals.
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