METHOD OF TREATING AND PREVENTING HYPERPARATHYROIDISM WITH ACTIVE VITAMIN D ANALOGS

• US 20100087404A1
• Filed: 05/06/2009
• Published: 04/08/2010
• Est. Priority Date: 04/03/1995
• Status: Abandoned Application

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Mazess, Richard B., Knutson, Joyce C., Strugnell, Stephen A.
• Application Number:
  US12/436,173
• Publication Number:
  US 20100087404A1
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/592 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 31/714 Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/16 Fluorine compounds
• CPC Class Codes: A61K 33/22 Boron compounds
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 5/20 for decreasing, blocking or antagonising the activity of PTH
• CPC Class Codes: C07C 401/00 Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation

Abstract

This invention relates to a method for treating or preventing hyperthyroidism secondary to chronic kidney disease by administering a sufficient amount of an active vitamin D analog utilizing a variety of effective treatment protocols.

Claims

1. A method of lowering or maintaining lowered serum parathyroid hormone level in human patients suffering from hyperparathyroidism secondary to chronic kidney disease, comprising administering to the patients an effective amount of a vitamin D analog to lower and maintain lowered serum parathyroid hormone levels, the analog comprising a compound of formula (I):

wherein A¹ and A² are each either hydrogen, or together represent a carbon-carbon double bond; and

X¹ is either hydrogen or hydroxyl.

2. A method in accordance with claim 1 wherein the active vitamin D analog is 1 α

-(OH)-vitamin D₂, 1 α

,24-(OH)₂-vitamin D₂ or 1 α

,24(S)—

(OH)₂-vitamin D₂.

3. A method in accordance with claim 2 wherein the active vitamin D analog is 1 α

-(OH)-vitamin D₂.

4. A method in accordance with claim 2, wherein the vitamin D analog is 1 α

,24-(OH)₂-vitamin D₂.

5. A method in accordance with claim 2, wherein the vitamin D analog is 1 α

,24(S)—

(OH)₂-vitamin D₂.

6. A method in accordance with claim 1, wherein the patients have a glomerular filtration rate (GFR) of <

60 mL/min/m².

7. A method in accordance with claim 1, wherein the patients have a glomerular filtration rate (GFR) of >

15-29 mL/min/m².

8. A method in accordance with claim 1, wherein the patients have a glomerular filtration rate (GFR) of ≧

30 mL/min/m².

9. A method in accordance with claim 1, wherein the chronic kidney disease is stage 1, stage 2, stage 3 or stage 4.

10. A method in accordance with claim 9, wherein the chronic kidney disease is stage 2 or stage 3.

11. A method in accordance with claim 1 wherein the amount of the vitamin D analog is administered parenterally or orally in combination with a pharmaceutically acceptable carrier.

12. A method in accordance with claim 11 wherein the amount of vitamin D analog is administered parenterally.

13. A method in accordance with claim 12 wherein the amount of vitamin D analog is administered intravenously.

14. A method in accordance with claim 11 wherein the amount of vitamin D analog is administered orally.

15. A method in accordance with claim 11 wherein the active vitamin D analog is co-administered with a phosphate binder.

16. A method in accordance with claim 12 wherein the active vitamin D compound is administered is by intravenous injection, nasopharyngeal or mucosal absorption, or transdermal absorption.

17. A method in accordance with claim 2 wherein the active vitamin D analog is administered in a weekly dosage of about 0.5 μ

.g to about 100 μ

g.

18. A method in accordance with claim 2 wherein the active vitamin D analog is administered in a weekly dosage of about 0.5 μ

g to about 25 μ

g.

19. A method in accordance with claim 17, wherein the vitamin D analog is in a 0.5 μ

g per unit dosage form.

20. A method in accordance with claim 17, wherein the vitamin D analog is in a 2.5 μ

g per unit dosage form.

21. A method in accordance with claim 1, wherein the active vitamin D is co-administered with a calcium-based phosphate binder.

22. A method in accordance with claim 1, wherein the vitamin D analog is co-administered with at least one agent characterized by said agent'"'"'s ability to reduce loss of bone mass, or bone mineral content in patients.

23. A method in accordance with claim 22, wherein the agent is other vitamin D compounds, conjugated estrogens, sodium fluorides, biphosphonates, cobalamin, pertussin toxin or boron.

24. A method in accordance with claim 22, wherein the vitamin D analog is administered before, after or concurrently with the other agent.

25. A method of treating hyperparathyroidism associated with chronic kidney disease, comprising administering to a subject suffering therefrom an amount of an active vitamin D analog which includes at least one of 1α

-OH-vitamin D₂;

1α

,24-(OH)₂-vitamin D₂; and

1α

,24(S)—

(OH)₂-vitamin D₂ sufficient to lower or maintain lowered blood parathyroid hormone (PTH) levels.

26. A method in accordance with claim 25, wherein the active vitamin D compound is 1α

-OH-vitamin D₂.

27. A method in accordance with claim 25, wherein the active vitamin D compound is 1α

,24-(OH)₂-vitamin D₂.

28. A method in accordance with claim 25, wherein the active vitamin D compound is 1α

,24(S)—

(OH)₂-vitamin D₂.

29. A method of treating hyperparathyroidism secondary to chronic kidney disease, comprising administering to a patient suffering therefrom an amount of 1α

-OH-vitamin D₂ sufficient to lower or maintain lowered blood parathyroid hormone (PTH) levels.

30. A method in accordance with claim 29, wherein the patient has a glomerular filtration rate of <

60 mL/min/m².

31. A method in accordance with claim 29, wherein the patients have a glomerular filtration rate (GFR) of >

15-29 mL/min/m².

32. A method in accordance with claim 29, wherein the patients have a glomerular filtration rate (GFR) of ≧

30 mL/min/m².

33. A method in accordance with claim 29, wherein the chronic kidney disease is stage 1, stage 2, stage 3 or stage 4.

34. A method in accordance with claim 33, wherein the chronic kidney disease is stage 2 or stage 3.