Claims for Patent: 11,433,083

Summary for Patent: 11,433,083

Title:	High-strength testosterone undecanoate compositions
Abstract:	The present disclosure is drawn to pharmaceutical compositions and oral dosage capsules containing testosterone undecanoate, as well as related methods. The capsule includes a capsule shell and a capsule fill. The capsule fill can include a solubilizer and about 14 wt % to about 35 wt % testosterone undecanoate based on the total capsule fill. The oral dosage capsule is such that when a single oral administration to a male subject of one or more capsules with a total testosterone undecanoate daily dose of about 350 mg to about 650 mg it provides a ratio of serum testosterone Cmax to serum testosterone Cave of about 2.7 or less. In yet another embodiment, a method for providing a serum concentration of testosterone within a target serum testosterone concentration Cave range for a male subject is provided.
Inventor(s):	Chandrashekar Giliyar, Basawaraj Chickmath, Nachiappan Chidambaram, Mahesh V. Patel, Srinivansan Venkateshwaran
Assignee:	Lipocine Inc
Application Number:	US16/412,360
Patent Claims:	1. A method for providing a serum concentration of testosterone within a target serum testosterone concentration Cave range for a male subject, comprising: 1) orally administering to the male subject an initial regimen including an initial daily dose of a testosterone undecanoate-containing composition, wherein the testosterone undecanoate comprises 15 to 20 total weight of composition % (wt %) of the testosterone undecanoate-containing composition and wherein the initial daily dose provides about 440 mg to about 490 mg of testosterone undecanoate to the male subject, and wherein the testosterone undecanoate-containing composition further comprises from 63 wt % to 68 wt % maize oil monoglycerides and 8 wt % to 16 wt % polyoxyl 40 hydrogenated castor oil; 2) determining a dose titration metric based on a measurement of serum testosterone concentration for the male subject on at least one titration node day within the initial regimen; and 3) orally administering to the male subject a maintenance regimen including a maintenance daily dose of testosterone undecanoate-containing composition, wherein the testosterone undecanoate-containing composition comprises 15 wt % to 20 wt % of the testosterone undecanoate-containing composition and wherein the maintenance regimen provides a maintenance daily dose of testosterone undecanoate to the subject based on the titration metric determined on the at least one titration node day of the initial regimen that is within 40% of the initial daily dose and sufficient to provide a serum testosterone plasma concentration within the target serum testosterone concentration Cave range of from about 300 ng/dL to about 1100 ng/dL. 2. The method of claim 1, further comprising: 4) determining the dose titration metric based on a measurement of serum testosterone concentration for the male subject on at least one titration node day within the maintenance regimen; 5) orally administering to the male subject a second maintenance regimen including a second maintenance daily dose of testosterone undecanoate-containing composition, wherein the testosterone undecanoate-containing composition comprises 15 wt % to 20 wt % of the testosterone undecanoate-containing composition and wherein the second maintenance regimen provides a second maintenance daily dose of testosterone undecanoate to the subject based on the titration metric determined on the at least one titration node day of the maintenance regimen sufficient to provide a serum testosterone plasma concentration within the target serum testosterone concentration Cave. 3. The method of claim 1, wherein the initial daily dose administered in the initial regimen is the same dosage amount as the daily dose administered in the maintenance regimen. 4. The method of claim 1, wherein the titration node day is any single day from day 15 to day 84 following the start of the initial regimen. 5. The method of claim 1, wherein the testosterone undecanoate dose titration is such that: i) if at time (t) of 1 to less than 3 hours following administration the serum testosterone concentration is less than 2.0 ng/mL there is an increase in dose, and if the serum testosterone concentration is more than 9.4 ng/mL there is a decrease in dose; ii) if at time (t) of 3 to less than 8 hours following administration the serum testosterone concentration is less than 4.1 ng/mL there is an increase in dose, and if the serum testosterone concentration is more than 18.1 ng/mL there is a decrease in dose; iii) if at time (t) of 8 to less than 12 hours following administration the serum testosterone concentration is less than 3.0 ng/mL there is an increase in dose and if the serum testosterone concentration is more than 7.8 ng/mL there is a decrease in dose; or iv) if at time (t) of 12 to less than 14 hours following administration the serum testosterone concentration is less than 1.4 ng/mL there is an increase in dose and if the serum testosterone concentration is more than 2.9 ng/mL there is a decrease in dose. 6. The method of claim 1, wherein the maintenance daily dose of the maintenance regimen provides an amount of testosterone undecanoate that is about 45% to about 155% of that of the initial daily dose. 7. The method of claim 1, wherein the target serum testosterone Cave range is about 300 ng/dL to about 1100 ng/dL and is achieved on or after day 84 following the start of the initial regimen. 8. The method of claim 1, wherein the initial daily dose during the initial regimen and the maintenance daily dose during the maintenance regimen includes twice-a-day administration of the testosterone undecanoate-containing composition in conjunction with meals. 9. The method of claim 1, wherein the method provides a serum testosterone Cavg in the range of 300 ng/dL to 1100 ng/dL in 75% or more of hypogonadal males after 84 days from the start of the initial regimen based on a minimum group size of 24 hypogonadal males. 10. The method of claim 1, wherein the method provides a serum testosterone Cmax in the range of 300 ng/dL to 1500 ng/dL in less than or equal to 85% of hypogonadal males after 84 days from the start of the initial regimen based on a minimum group size of 24 hypogonadal males. 11. The method of claim 1, wherein the method provides a serum testosterone Cmax in the range of 1800 ng/dL to 2500 ng/dL in about 5% or less of hypogonadal males after 84 days from the start of the initial regimen based on a minimum group size of 24 hypogonadal males. 12. The method of claim 1, wherein the method provides a serum testosterone Cmax of 2500 ng/dL in about 1% or less of hypogonadal males after 84 days from the start of the initial regimen based on a minimum group size of 24 hypogonadal males. 13. The method of claim 1, wherein the male subject is a hypogonadal male.