Onapristone extended-release compositions and methods
Onapristone extended-release formulations and methods of administering onapristone extended-release formulations are provided. Onapristone extended-release formulations provide sufficient therapeutic activity as compared to immediate-release formulations with reduced potential for adverse side effects.
1. A method of administering onapristone to a patient having cancer comprising administering an extended-release onapristone pharmaceutical composition to the patient, wherein the extended-release onapristone pharmaceutical composition comprises about 5% (wt/wt) onapristone, about 20.5% (wt/wt) lactose monohydrate, about 20.5% (wt/wt) microcrystalline cellulose, about 20% (wt/wt) pregelatinized starch, about 33% (wt/wt) hydroxypropyl methylcellulose, about 0.5% silicon dioxide, and about 0.5% magnesium stearate.
2. The method of claim 1 , wherein the extended-release onapristone pharmaceutical composition is administered twice per day.
3. The method of claim 1 , wherein the onapristone is at least about 98% pure.
4. The method of claim 1 , wherein the cancer expresses the progesterone receptor.
5. The method of claim 4 , wherein the cancer is selected from the group consisting of breast, prostate, ovarian, and uterine endometrioid cancers.
6. A method of treating a human subject having a cancer which expresses the progesterone receptor comprising administering an extended-release onapristone pharmaceutical composition to the human subject wherein the extended-release onapristone pharmaceutical composition comprises about 5% (wt/wt) onapristone, about 20.5% (wt/wt) lactose monohydrate, about 20.5% (wt/wt) microcrystalline cellulose, about 20% (wt/wt) pregelatinized starch, about 33% (wt/wt) hydroxypropyl methylcellulose, about 0.5% silicon dioxide, and about 0.5% magnesium stearate, and wherein the AUC of onapristone following the administration of the extended-release onapristone pharmaceutical composition is at least about 1578 ng*h/ml over about 8-12 hours.
7. The method of claim 6 , wherein the extended-release onapristone pharmaceutical composition is administered to the human subject once per day.
8. A method of treating a human subject having a cancer which expresses the progesterone receptor comprising administering an extended-release onapristone pharmaceutical composition wherein the extended-release onapristone pharmaceutical composition comprises about 5% (wt/wt) onapristone, about 20.5% (wt/wt) lactose monohydrate, about 20.5% (wt/wt) microcrystalline cellulose, about 20% (wt/wt) pregelatinized starch, about 33% (wt/wt) hydroxypropyl methylcellulose, about 0.5% silicon dioxide, and about 0.5% magnesium stearate, and wherein the Cmax of onapristone following the administration of the extended-release onapristone pharmaceutical composition in the human subject is at least about 240 ng/ml over about 8-12 hours.
9. The method of claim 8 , wherein the extended-release onapristone pharmaceutical composition is administered to the human subject once per day.
10. A method of treating a human subject having a cancer which expresses the progesterone receptor comprising administering an extended-release pharmaceutical composition wherein the extended-release onapristone pharmaceutical composition comprises about 5% (wt/wt) onapristone, about 20.5% (wt/wt) lactose monohydrate, about 20.5% (wt/wt) microcrystalline cellulose, about 20% (wt/wt) pregelatinized starch, about 33% (wt/wt) hydroxypropyl methylcellulose, about 0.5% silicon dioxide, and about 0.5% magnesium stearate, and wherein a steady state plasma concentration of onapristone following the administration of the extended-release onapristone pharmaceutical composition in the human subject is achieved at about 8 days.
11. The method of claim 10 , wherein the extended-release onapristone pharmaceutical composition is administered to the human subject once per day.
12. The method of claim 6 , wherein the cancer which expresses the progesterone receptor is selected from group consisting of breast cancer, endometrial cancer, prostate cancer, ovarian, and uterine cancers.
13. The method of claim 1 , wherein the extended-release onapristone pharmaceutical composition is administered once per day.
14. The method of claim 6 , wherein the extended-release onapristone pharmaceutical composition is administered twice per day.
15. The method of claim 8 , wherein the extended-release onapristone pharmaceutical composition is administered twice per day.
16. The method of claim 10 , wherein the extended-release onapristone pharmaceutical composition is administered twice per day.