Details for Patent: 9,918,940

Title:	Methods for controlled release oral dosage of a vitamin D compound
Abstract:	A stable, controlled release formulation for oral dosing of vitamin D compounds is disclosed. The formulation is prepared by incorporating one or more vitamin D compounds into a solid or semi-solid mixture of waxy materials. Oral dosage forms can be prepared by melt-blending the components described herein and filling gelatin capsules with the formulation.
Inventor(s):	Bishop; Charles W. (Miami Beach, FL), Tabash; Samir P. (Whitby, CA), Agudoawu; Sammy A. (Mississauga, CA), White; Jay A. (Newmarket, CA), Crawford; Keith H. (Highlands Ranch, CO), Messner; Eric J. (Lake Forest, IL), Petkovich; P. Martin (Kingston, CA)
Assignee:	OPKO RENAL, LLC (N/A) OPKO IRELAND GLOBAL HOLDINGS, LTD. (Grand Cayman, KY)
Filing Date:	Jun 16, 2014
Application Number:	14/305,863
Claims:	1. A method of increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral-dosage form comprising 25-hydroxyvitamin D to raise or maintain the patient's blood 1,25-dihydroxyvitamin D level to at least about 25 pg/mL without causing hypercalcemia, wherein the patient has a vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof, and the 25-hydroxyvitamin D is administered in an amount of 1 to 1000 .mu.g per unit dose. 2. The method of claim 1, wherein the 25-hydroxyvitamin D comprises 25-hydroxyvitamin D.sub.3, 25-hydroxyvitamin D.sub.2, or a combination thereof. 3. The method of claim 1, wherein the 25-hydroxyvitamin D comprises 25-hydroxyvitamin D.sub.3. 4. The method of claim 1, wherein the 25-hydroxyvitamin D consists of 25-hydroxyvitamin D.sub.3. 5. The method of claim 1, wherein said administration maintains blood 1,25-dihydroxyvitamin D level above 25 pg/mL. 6. The method of claim 1, wherein said administration raises or maintains blood 1,25-dihydroxyvitamin D level to at least 30 pg/mL. 7. The method of claim 1, wherein said administration raises or maintains blood 1,25-dihydroxyvitamin D level to a concentration in a range of about 25 pg/mL to about 65 pg/mL. 8. The method of claim 1, wherein the effective amount of said controlled release, oral dosage form of 25-hydroxyvitamin D does not increase total serum or blood level of 1,25-dihydroxyvitamin D by greater than 75 pg/mL after administration of said dose. 9. The method of claim 1, wherein said administration is continued to maintain said increased blood level of 1,25-dihydroxyvitamin D for at least one month. 10. The method of claim 9, wherein said administration is continued to maintain said increased blood level of 1,25-dihydroxyvitamin D for at least three months. 11. The method of claim 10, wherein said administration is continued to maintain said increased blood level of 1,25-dihydroxyvitamin D for at least six months. 12. The method of claim 1, wherein the patient is vitamin D insufficient or deficient. 13. The method of claim 1, wherein the patient is vitamin D replete. 14. The method of claim 1, wherein the patient has a disease selected from the group consisting of hyperparathyroidism, secondary hyperparathyroidism, and combinations thereof. 15. A method of increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral dosage form comprising 25-hydroxyvitamin D.sub.3 to increase or maintain blood 1,25-dihydroxyvitamin D level in a range of about 25 pg/mL to about 65 pg/mL and continuing said administering to maintain said increased blood 1,25-dihydroxyvitamin D level for at least one month without causing hypercalcemia, wherein the patient has vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof and wherein the 25-hydroxyvitamin D.sub.3 is administered in an amount of 1 to 1000 .mu.g per unit dose. 16. A method of increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral dosage form consisting of 25-hydroxyvitamin D.sub.3 to increase or maintain blood 1,25-dihydroxyvitamin D level to at least about 25 pg/mL without causing hypercalcemia wherein the effective amount of said controlled release, oral dosage form of 25-hydroxyvitamin D does not increase total serum or blood level of 1,25-dihydroxyvitamin D by greater than 75 pg/mL after administration of said dose, wherein the patient has a vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof and wherein the 25-hydroxyvitamin D.sub.3 is administered in an amount of 1 to 1000 .mu.g per unit dose. 17. A method of increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral dosage form comprising 25-hydroxyvitamin D to raise or maintain blood 1,25-dihydroxyvitamin D level to at least about 25 pg/mL without causing substantially increased catabolism of the administered 25-hydroxyvitamin D or hypercalcemia, wherein the patient has a vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof and wherein the 25-hydroxyvitamin D.sub.3 is administered in an amount of 1 to 1000 .mu.g per unit dose.