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US 12,576,090 B1Granted
Oral brexanolone compositions and methods of preparation and use
OwnerNachiappan Chidambaram, Mahesh V. Patel +5inventors
InventorsNachiappan Chidambaram, Mahesh V. Patel, Jonathan Ogle, Kongnara Papangkorn, Samuel Akapo, Joel Frank, Benjamin J. Bruno
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Abstract
Disclosed is a method and a brexanolone containing oral composition for treating CNS disorders such as depression. An embodiment of the invention comprises orally administering a brexanolone containing composition to a subject having a CNS disorder. The composition and methods disclosed herein exhibit effective oral absorption/bioavailability and a predetermined ratio of bioavailability in a fed state administration relative to a fasted state administration.
Claims30
A method for use in treating depression comprising administering to a subject having depression a pharmaceutical composition (PC) comprising brexanolone or a prodrug thereof (brex-P) and at least one additive (BPC),
- wherein administration of said BPC without food to a group of recipients (fasted administration) results in a group mean brexanolone level in said group of recipients of a predetermined value for Cmax and AUC (fasted PK values), and
- wherein administration of said BPC with food comprising a high fat content to a group of recipients (Hi fed administration) results in a group mean brexanolone level in said group of recipients of a predetermined value for Cmax and AUC (Hi fed PK values), and
- wherein administration of said BPC results in at least one of the following comprising:
- a geometric mean ratio of at least one fasted PK value resulting from a first fasted administration to a first group of recipients that falls within a range of about 70% to about 143% of a geometric mean ratio of at least one corresponding fasted PK value resulting from a second fasted administration to said first group of recipients,
- a geometric mean ratio of at least one fasted PK value resulting from a fasted administration to a first group of recipients that falls within a range of about 70.0% to about 143.0% of a geometric mean ratio of at least one corresponding fasted PK value resulting from a fasted administration to a second group of recipients,
- a geometric mean ratio of at least one fasted PK value resulting from a first fasted administration to a first group of recipients that falls within a range of about 70% to about 143% of a 90% CI of geometric mean ratio of at least one corresponding fasted PK value resulting from a second fasted administration to said first group of recipients,
- a geometric mean ratio of at least one fasted PK value resulting from a fasted administration to a first group of recipients that falls within a range of about 70.0% to about 143.0% of a 90% CI of a geometric mean ratio of at least one corresponding fasted PK value resulting from a fasted administration to a second group of recipients,
- a geometric mean ratio of at least one Hi fed PK value resulting from a first Hi fed administration to a first group of recipients that falls within a range of about 70.0% to about 143.0% of a geometric mean ratio of at least one corresponding Hi fed PK value resulting from a second Hi fed administration to said first group of recipients,
- a geometric mean ratio of at least one Hi fed PK value resulting from a Hi fed administration to a first group of recipients that falls within a range of about 70.0% to about 143.0% of a geometric mean ratio of at least one corresponding Hi fed PK value resulting from a Hi fed administration to a second group of recipients,
- a geometric mean ratio of at least one Hi fed PK value resulting from a first Hi fed administration to a first group of recipients that falls within a range of about 70.0% to about 143.0% of a 90% CI of a geometric mean ratio of at least one corresponding Hi fed PK value resulting from a second Hi fed administration to said first group of recipients, and
- a geometric mean ratio of at least one Hi fed PK value resulting from a Hi fed administration to a first group of recipients that falls within a range of about 70.0% to about 143.0% of a 90% CI of a geometric mean ratio of at least one corresponding Hi fed PK value resulting from a Hi fed administration to a second group of recipients.
8 more elements
A method for use in treating depression comprising administering to a subject having depression a PC comprising BPC,
- wherein administration of said BPC without food to a group of recipients (fasted administration) results in a group mean brexanolone level in said group of recipients of a predetermined value for Cmax, AUC, and Tmax (fasted PK values), and
- wherein administration of said BPC with food comprising a high fat content to a group of recipients (Hi fed administration) results in a group mean brexanolone level in said group of recipients of a predetermined value for Cmax, AUC, and Tmax (Hi fed PK values), and wherein
- administration of said BPC results in at least one of the following comprising:
- in a Hi fed administration to a first group of recipients relative to a fasted administration to said first group of recipients at least one of:
- substantially no change in Tmax, and
- an increase of about 2.25 fold to about 10 fold in at least one Hi fed PK value relative to at least one corresponding fasted PK value, and
- in a Hi fed administration to a first group of recipients relative to a fasted administration to a second group of recipients at least one of:
- substantially no change in Tmax, and
- an increase of about 2.25 fold to about 10 fold in at least one Hi fed PK value relative to at least one corresponding fasted PK value.
6 more elements
A method for use in treating depression comprising administering to a subject having depression a PC comprising BPC,
- wherein administration of said BPC without food to a group of recipients (fasted administration) results in a group mean brexanolone level in said group of recipients of a predetermined value for Cmax, AUC, and Tmax (fasted PK values), and
- wherein administration of said BPC with food comprising a high fat content to a group of recipients (Hi fed administration) results in a group mean brexanolone level in said group of recipients of a predetermined value for Cmax, AUC, and Tmax (Hi fed PK values), and wherein
- administration of said BPC results in at least one of the following comprising:
- in a Hi fed administration to a first group of recipients relative to a fasted administration to said first group of recipients at least one of:
- substantially no change in Tmax,
- an increase of about 76 ng/ml to about 356 ng/ml said Hi fed Cmax PK value relative to said fasted Cmax PK value, and
- an increase of about 250 h*ng/ml to about 810 h*ng/ml in said Hi fed AUC PK value relative to said fasted AUC PK value, and
- in a Hi fed administration to a first group of recipients relative to a fasted administration to a second group of recipients at least one of:
- substantially no change in Tmax,
- an increase of about 76 ng/ml to about 356 ng/ml in at least one Hi fed PK value relative to at least one corresponding fasted PK value,
- an increase of about 250 h*ng/ml to about 810 h*ng/ml in said Hi fed AUC PK value relative to said fasted AUC PK value.
8 more elements
A method for use in treating depression comprising administering a treatment regimen to a subject having depression, said regimen comprising administering a dose of two of about 250 mg tablets comprising brexanolone at an interval frequency of about eight hours for a duration of at least one of six doses, seven doses, and eight doses.
Dependencies are inferred from the claim text.