Claims for Patent: 9,498,486

Summary for Patent: 9,498,486

Title:	Method 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), Messner; Eric J. (Lake Forest, IL), Petkovich; P. Martin (Kingston, CA), Crawford; Keith H. (Lone Tree, CO)
Assignee:	OPKO RENAL, LLC (Miami, FL) OPKO IRELAND GLOBAL HOLDINGS, LTD. (Grand Cayman, KY)
Application Number:	15/231,357
Patent Claims:	1. A method of treating secondary hyperparathyroidism in a human patient having Chronic Kidney Disease (CKD), comprising administering to the human patient having CKD an effective amount of a sustained release, oral dosage form of 25-hydroxyvitamin D to treat the secondary hyperparathyroidism and reduce the patient's serum parathyroid hormone level, wherein the administration avoids transient increases in blood levels of 25-hydroxyvitamin D of greater than 3 ng/mL following a unit dose. 2. The method of claim 1, comprising administering 30 .mu.g or 60 .mu.g of 25-hydroxyvitamin D.sub.3. 3. The method of claim 1, wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier. 4. The method of claim 3, wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier, a lipoidic agent, and an oily vehicle for the 25-hydroxyvitamin D compound. 5. The method of claim 1, comprising administering said oral dosage on a schedule of once per day. 6. The method of claim 1, wherein the patient has CKD Stage 5. 7. The method of claim 1, wherein the patient has CKD Stage 1 or 2. 8. The method of claim 1, wherein the patient has CKD Stage 3 or 4. 9. A method of treating secondary hyperparathyroidism in a human patient having Chronic Kidney Disease (CKD), comprising administering to the human patient having CKD an effective amount of a sustained release, oral dosage form of 25-hydroxyvitamin D to treat the secondary hyperparathyroidism and reduce the patient's serum parathyroid hormone level, wherein the sustained release is effected over a period of at least four hours. 10. The method of claim 9, comprising administering 30 .mu.g or 60 .mu.g of 25-hydroxyvitamin D.sub.3. 11. The method of claim 9, wherein the administration avoids transient increases in blood levels of 25-hydroxyvitamin D of greater than 3 ng/mL following a unit dose. 12. The method of claim 9, wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier. 13. The method of claim 9, comprising administering said oral dosage on a schedule of once per day. 14. The method of claim 9, wherein the patient has CKD Stage 5. 15. The method of claim 9, wherein the patient has CKD Stage 1 or 2. 16. The method of claim 9, wherein the patient has CKD Stage 3 or 4. 17. A method of treating secondary hyperparathyroidism in a human patient having Chronic Kidney Disease (CKD), comprising administering to the human patient having CKD an effective amount of a sustained release, oral dosage form of 25-hydroxyvitamin D to treat the secondary hyperparathyroidism and reduce the patient's serum parathyroid hormone level, such that (a) the ratio of the maximum serum concentration within 24 hours after administration of the vitamin D compound to the concentration 24 hours after administration (Cmax.sub.24hr/C.sub.24hr) is reduced as compared to an equivalent amount of the vitamin D compound administered by an immediate-release, oral dosage form and/or (b) the time for the plasma concentration of the vitamin D compound to reach its maximum in a dose interval following administration (Tmax) is increased as compared to Tmax for an equivalent amount of the vitamin D compound administered by an equivalent immediate-release, oral dosage form, wherein the vitamin D compound comprises 25-hydroxyvitamin D.sub.3. 18. The method of claim 17, comprising administering 30 .mu.g or 60 .mu.g of 25-hydroxyvitamin D.sub.3. 19. The method of claim 17, wherein the administration avoids transient increases in blood levels of 25-hydroxyvitamin D of greater than 3 ng/mL following a unit dose. 20. The method of claim 17, wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier. 21. The method of claim 17, comprising administering said oral dosage on a schedule of once per day. 22. The method of claim 17, wherein the patient has CKD Stage 5. 23. The method of claim 17, wherein the patient has CKD Stage 1 or 2. 24. The method of claim 17, wherein the patient has CKD Stage 3 or 4. 25. A method of treating a disease or condition, comprising administering to a human patient 30 .mu.g or 60 .mu.g of an extended release, oral dosage form of 25-hydroxyvitamin D.sub.3 once daily, wherein the disease or condition is secondary hyperparathyroidism in an adult human patient having Chronic Kidney Disease (CKD) Stage 3 or 4 and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. 26. The method of claim 25, wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier. 27. The method of claim 26, wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier, a lipoidic agent, and an oily vehicle for the 25-hydroxyvitamin D compound. 28. The method of claim 25, wherein the patient has CKD Stage 5. 29. The method of claim 25, wherein the patient has CKD Stage 1 or 2. 30. The method of claim 25, wherein the patient has CKD Stage 3 or 4.