Hydroxyprogesterone caproate compositions and methods of use in preventing preterm birth

A method of preventing or reducing the likelihood of recurrent PTB in a subject, said method comprising orally administering to said subject an oral dosage form having an effective amount of a pharmaceutical composition comprising HPC, and

• wherein said administration results in a Cmin of HPC in said subject of about 4 ng/ml to about 16 ng/ml, and
• wherein said administration comprises a dosing regimen comprising at least one of a once-a-day administration, a twice-a-day administration, and a three-times-a-day administration, and
• wherein said dosing regimen comprises a total daily administration of HPC of about 1,200 mg to about 1600 mg, and
• wherein said method comprises at least one of:
• said dosing regimen begins at a GA of a fetus of said subject of at least one of no more than 14 weeks, no more than 15 weeks, no more than 16 weeks, no more than 17 weeks, and less than 18 weeks. and
• said subject has had a qualified PTB of less than at least one of 35 weeks, 34 weeks, 33 weeks, and 32 weeks, and
• wherein in comparison to the administration of a placebo, said administration of said HPC results in a minimum improvement of a total NCI outcome of a neonate of said subject of at least one of 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, and 50%, and a plurality of:
• a reduced likelihood of death of a neonate of said subject prior to hospital discharge thereof,
• an improvement in a grade III or IV intraventricular hemorrhage of a neonate of said subject,
• an improvement in respiratory distress syndrome of a neonate of said subject,
• an improvement of bronchopulmonary dysplasia of a neonate of said subject,
• an improvement of necrotizing enterocolitis of a neonate of said subject,
• an improvement of proven sepsis of a neonate of said subject,
• a reduction in a length of stay (LOS) of a neonate of said subject in a medical care facility of at least three days, and
• a minimum responder rate of at least one of 5%, 7%, 9%, 10%, 12%, 13%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, and 50% for said subject giving birth at no earlier than at least one of 32 weeks, 35 weeks, and 37 weeks, when said HPC is administered to a group of subjects.

A method of preventing or reducing the likelihood of recurrent PTB in a subject, said method comprising orally administering to said subject an oral dosage form having an effective amount of a pharmaceutical composition comprising HPC, and

• wherein said administration results in a Cmin of HPC in said subject of about 4 ng/ml to about 16 ng/ml, and
• wherein said administration comprises a dosing regimen comprising at least one of a once-a-day administration, a twice-a-day administration, and a three-times-a-day administration, and
• wherein said dosing regimen comprises a total daily administration of HPC of about 1,200 mg to about 1600 mg, and
• wherein said method comprises at least one of:
• said dosing regimen begins at a GA of a fetus of said subject of at least one of no more than 14 weeks, no more than 15 weeks, no more than 16 weeks, no more than 17 weeks, and less than 18 weeks, and
• said subject has had a qualified PTB of less than at least one of 35 weeks, 34 weeks, 33 weeks, and 32 weeks, and
• wherein in comparison to the administration of a placebo, said administration of said HPC results in a minimum improvement of a total NCI outcome of a neonate of said subject of at least one of 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, and 50%, and
• wherein said administration results in an at least one of:
• a Cmax in said subject in the range of about 35 ng/ml to about 180 ng/ml,
• a Cavg in said subject in the range of about 6 ng/ml to about 50 ng/ml,
• an effective level of HPC in said subject in about one day to about one week,
• a Tmax in the range of about 2 hours to about 12 hours post administration,
• a Cavg post administration efficacy minimum threshold level (EMTL) of plasma HPC concentration in said subject in less than at least one of 7 days, 6 days, 5 days, 4 days, 3 days, and 2 days, and
• a daily minimum fluctuation ratio of at least one of 6, 8, 10, 13, 15, 18, 20, 25, 30, 35, 40, and 44.

A method of preventing or reducing the likelihood of recurrent PTB in a subject, said method comprising orally administering to a subject an oral dosage form having an effective amount of a pharmaceutical composition comprising HPC, and

• wherein said administration results in a Cmin of HPC in said subject of about 4 ng/ml to about 16 ng/ml, and
• wherein said administration comprises a dosing regimen comprising at least one of a once-a-day administration, a twice-a-day administration, and a three-times-a-day administration, and
• wherein said dosing regimen comprises a total daily administration of HPC of about 1,200 mg to about 1600 mg, and
• wherein said method comprises at least one of:
• wherein said dosing regimen begins at a GA of a fetus of said subject of at least one of no more than 14 weeks, no more than 15 weeks, no more than 16 weeks, no more than 17 weeks, and less than 18 weeks, and
• said subject has had a qualified PTB of less than at least one of 35 weeks, 34 weeks, 33 weeks, and 32 weeks, and
• wherein in comparison to the administration of a placebo, said administration of said HPC results in a minimum improvement of a total NCI outcome of a neonate of said subject of at least one of 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, and 50%, and
• wherein said subject is at altered risk of PTB.