Claims for Patent: 10,493,084

Summary for Patent: 10,493,084

Title:	Adjunctive therapy with 25-hydroxyvitamin D and articles therefor
Abstract:	Methods, compositions, and kits for adjunctive therapy using 25-hydroxyvitamin D are disclosed. The 25-hydroxyvitamin D may be administered with an agent that increases the risk of hypocalcemia, such as cinacalcet or a salt thereof, and/or an anticancer agent. The adjunctive therapy is effective to treat and prevent iatrogenic hypocalcemia and/or secondary hyperparathyroidism, as well as delay cancer progression and the time to a post-treatment skeletal related event.
Inventor(s):	Petkovich; P. Martin (Kingston, CA), Melnick; Joel Z. (Evanston, IL), White; Jay A. (Newmarket, CA), Tabash; Samir P. (Whitby, CA), Bishop; Charles W. (Miami Beach, FL), Peers; Susan (Toronto, CA), Strugnell; Stephen A. (Bay Harbor Islands, FL)
Assignee:	OPKO IRELAND GLOBAL HOLDINGS, LTD. (Grand Cayman, KY)
Application Number:	16/243,549
Patent Claims:	1. A method of managing iatrogenic hypocalcemia and secondary hyperparathyroidism in a patient receiving therapy with cinacalcet or a salt thereof, comprising administering to said patient a pharmaceutical formulation comprising (a) a 25-hydroxyvitamin D compound and (b) an agent that increases the risk of hypocalcemia, optionally cinacalcet or a salt thereof. 2. The method of claim 1, wherein the patient has impaired renal function, optionally associated with Chronic Kidney Disease Stage 1, 2, 3, 4, or 5. 3. The method of claim 1, wherein the patient is receiving dialysis. 4. The method of claim 1, wherein the patient is not on dialysis. 5. The method of claim 1, wherein the effective amount of 25-hydroxyvitamin D is effective to restore or maintain the patient's serum calcium level to at least about 8.0 mg/dL, optionally in a range of about 8.3 mg/dL to about 11.6 mg/dL. 6. The method of claim 1, wherein the effective amount of 25-hydroxyvitamin D is effective to safely increase the patient's serum level of 25-hydroxyvitamin D to at least 30 ng/mL, optionally in a range of about 30 ng/mL to about 100 ng/mL. 7. The method of claim 1, wherein the effective amount of 25-hydroxyvitamin D is effective to decrease the patient's serum parathyroid hormone level, optionally by 30% or more. 8. The method of claim 1, wherein the effective amount of 25-hydroxyvitamin D is administered in an oral modified release formulation, optionally a sustained release formulation. 9. The method of claim 1, wherein the 25-hydroxyvitamin D is co-administered in an oral formulation comprising cinacalcet or a salt thereof. 10. 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. 11. The method of claim 10, wherein the 25-hydroxyvitamin D comprises 25-hydroxyvitamin D.sub.3. 12. The method of claim 1, wherein the 25-hydroxyvitamin D is administered in a dosage of 1 mcg to 1000 mcg per day. 13. The method of claim 1, wherein the cinacalcet or salt thereof comprises cinacalcet HCI. 14. The method of claim 1, wherein the patient is receiving cinacalcet administered in a dosage of 1 mg to 400 mg per day. 15. A method of treating secondary hyperparathyroidism in Chronic Kidney Disease in a patient on dialysis comprising administering to said patient an effective amount of a 25-hydroxyvitamin D compound by modified release and an effective dose of cinacalcet or a salt thereof in an amount of less than 360 mg daily, wherein said effective amount of cinacalcet is a reduced dose compared to the effective dose of cinacalcet in the absence of said 25-hydroxyvitamin D administration. 16. The method of claim 15, comprising an initial dose of cinacalcet in a range of about 20 mg to about 25 mg once daily. 17. A method of treating hypercalcemia in a patient with parathyroid carcinoma, comprising administering to said patient an effective amount of a 25-hydroxyvitamin D compound by modified release and an effective dose of cinacalcet or a salt thereof in an amount of less than 360 mg daily, wherein said effective amount of cinacalcet or a salt thereof is a reduced dose compared to the effective dose of cinacalcet in the absence of said 25-hydroxyvitamin D administration. 18. A method of treating severe hypercalcemia in a patient with primary hyperparathyroidism who is unable to undergo parathyroidectomy, comprising administering to said patient an effective amount of a 25-hydroxyvitamin D compound by modified release and an effective dose of cinacalcet or a salt thereof in an amount of less than 360 mg daily, wherein said effective amount of cinacalcet or a salt thereof is a reduced dose compared to the effective dose of cinacalcet in the absence of said 25-hydroxyvitamin D administration. 19. The method of claim 17, comprising an initial dose of cinacalcet in a range of about 20 mg to about 25 mg once daily. 20. The method of claim 1, wherein the effective amount of 25-hydroxyvitamin D is in a range of about 100 mcg to about 300 mcg. 21. A method of treating a patient treated with an agent that increases the risk of hypocalcemia to (i) increase bone mineral density, (ii) decrease the blood level of a bone resorption marker, (iii) treat bone pain, (iv) increase the time to the first post-treatments skeletal-related event, said method comprising administering to the patient an effective amount of 25-hydroxyvitamin D, optionally, wherein 25-hydroxyvitamin D is administered in an amount effective to effectively and safely restore blood 25-hydroxyvitamin D levels to at least 30 ng/mL and to maintain blood 25-hydroxyvitamin D levels at such optimal levels. 22. A method of lowering elevated serum parathyroid hormone levels and/or stabilizing serum calcium levels in a patient having a bone metastasis and treated with an antiresorptive agent comprising administering an effective amount of 25-hydroxyvitamin D.

Details for Patent 10,493,084

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2034-08-07