Rapid establishment and/or termination of substantial steady-state drug delivery

• US 20110076317A1
• Filed: 09/21/2010
• Published: 03/31/2011
• Est. Priority Date: 09/28/2009
• Status: Active Grant

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Alessi, Thomas R., Luskey, Kenneth L.
• Granted Patent: US 8,298,561 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 5/0013 Implantable devices or invasive measures
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61M 2005/14513 with secondary fluid driving or regulating the infusion
• CPC Class Codes: A61M 2205/04 implanted
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present invention is directed to treatment methods for a disease or condition, in a subject in need of such treatment, that provide alternatives to treatment by injection that give, relative to treatment by injection, improved treatment outcomes, 100% treatment compliance, reduced side effects, and rapid establishment and/or termination of substantial steady-state drug delivery. The method typically includes providing continuous delivery of a drug from an implanted osmotic delivery device, wherein substantial steady-state delivery of the drug at therapeutic concentrations is typically achieved within about 7 days or less after implantation of the osmotic delivery device in the subject and the substantial steady-state delivery of the drug from the osmotic delivery device is continuous over a period of at least about 3 months. In one embodiment, the present invention is directed to treatment of type 2 diabetes mellitus using incretin mimetics.

Claims

1. A method of treating type 2 diabetes mellitus in a subject in need of treatment, comprising

providing continuous delivery of an incretin mimetic from an osmotic delivery device, wherein substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within a time period of about 7 days or less after implantation of the osmotic delivery device in the subject and the substantial steady-state delivery of the incretin mimetic from the osmotic delivery device is continuous over an administration period of at least about 3 months.

2. The method of claim 1, wherein substantial steady-state delivery of the incretin mimetic at therapeutic concentrations is achieved after implantation of the osmotic delivery device in the subject within a time period selected from the group consisting of about 5 days or less, about 4 days or less, about 3 days or less, about 2 days or less, about 1 day or less.

3. The method of claim 1, wherein the substantial steady-state delivery of the incretin mimetic from the osmotic delivery device is continuous over an administration period selected from the group consisting of at least about 3 months to about a year, at least about 4 months to about a year, at least about 5 months to about a year, at least about 6 months to about a year, at least about 8 months to about a year, and at least about 9 months to about a year.

4. The method of claim 1, further comprising providing a significant decrease in the subject'"'"'s fasting plasma glucose concentration after implantation of the osmotic delivery device in the subject, relative to the subject'"'"'s fasting plasma glucose concentration before implantation of the osmotic delivery device, within a number of days selected from the group consisting of about 7 days or less, about 6 days or less, about 5 days or less, about 4 days or less, about 3 days or less, about 2 days or less, and about 1 day or less.

5. The method of claim 4, wherein the significant decrease in the subject'"'"'s fasting plasma glucose concentration is achieved, relative to the subject'"'"'s fasting plasma glucose concentration before implantation of the osmotic device, within about 1 day of implantation of the osmotic delivery device in the subject.

6. The method of claim 4, wherein the significant decrease in fasting plasma glucose is maintained over the administration period.

7. The method of claim 1, further comprising the capability to terminate the continuous delivery of the incretin mimetic such that the concentration of the incretin mimetic is substantially undetectable in a blood sample from the subject within about 6 half-lives or less of the incretin mimetic after termination of continuous delivery, within about 5 half-lives or less of the incretin mimetic after termination of continuous delivery, within about 4 half-lives or less of the incretin mimetic after termination of continuous delivery, or within about 3 half-lives or less of the incretin mimetic after termination of continuous delivery.

8. The method of claim 7, wherein termination of continuous delivery is removal of the osmotic delivery device from the subject.

9. The method of claim 7, wherein the incretin mimetic is detected by a radioimmunoassay.

10. The method of claim 1, wherein the osmotic delivery device comprises

an impermeable reservoir comprising interior and exterior surfaces and first and second open ends,

a semi-permeable membrane in sealing relationship with the first open end of the reservoir,

an osmotic engine within the reservoir and adjacent the semi-permeable membrane,

a piston adjacent the osmotic engine, wherein the piston forms a movable seal with the interior surface of the reservoir, the piston divides the reservoir into a first chamber and a second chamber, the first chamber comprising the osmotic engine,

a suspension formulation, wherein the second chamber comprises the suspension formulation and the suspension formulation is flowable and comprises the incretin mimetic, and

a diffusion moderator inserted in the second open end of the reservoir, the diffusion moderator adjacent the suspension formulation.

12. The method of claim 10, wherein the suspension formulation comprises

a particle formulation comprising the incretin mimetic, and

a vehicle formulation.

13. The method of claim 12, wherein the incretin mimetic comprises an exenatide peptide, a peptide analog thereof, or a peptide derivative thereof.

14. The method of claim 13, wherein the incretin mimetic is exenatide having the amino acid sequence of exendin-4.

15. The method of claim 14, wherein the continuous delivery provides to the subject a mcg/day dose of exenatide selected from the group consisting of about 10 mcg/day, about 20 mcg/day, about 30 mcg/day, about 40 mcg/day, about 60 mcg/day, or about 80 mcg/day.

16. The method of claim 14, further comprising the capability to terminate the continuous delivery such that the concentration of exenatide is substantially undetectable in a blood sample from the subject after termination of continuous delivery in a number of hours selected from the group consisting of less than about 72 hours, less than about 48 hours, less than about 24, and less than about 12 hours.

17. The method of claim 1, wherein the method further comprises a first continuous administration period of the incretin mimetic at a first mcg/day dose that is followed by a second continuous administration period providing a dose escalation of the incretin mimetic to a second mcg/day dose, wherein the second mcg/day dose is greater than the first mcg/day dose.

18. The method of claim 17, wherein the first mcg/day dose is delivered by a first osmotic delivery device and the second mcg/day dose is delivered by a second osmotic delivery device, and delivery of the incretin mimetic from at least the first or the second osmotic delivery device is continuous over the administration period of at least about 3 months.

19. The method of claim 18, wherein the second mcg/day dose is at least two times greater than the first mcg/day dose.

20. The method of claim 17, wherein the method comprises at least one more continuous administration period providing a dose escalation of the incretin mimetic to a higher mcg/day dose relative to the second mcg/day dose.

21. The method of claim 17, wherein the incretin mimetic is an exenatide, and the first mcg/day dose followed by the second mcg/day dose for continuous delivery are selected from the group consisting of:

about 10 mcg/day followed by about 20 mcg/day;

about 10 mcg/day followed by about 40 mcg/day;

about 10 mcg/day followed by about 60 mcg/day;

about 10 mcg/day followed by about 80 mcg/day;

about 20 mcg/day followed by about 40 mcg/day;

about 20 mcg/day followed by about 60 mcg/day;

about 20 mcg/day followed by about 80 mcg/day;

about 40 mcg/day followed by about 60 mcg/day;

about 40 mcg/day followed by about 80 mcg/day; and

about 60 mcg/day followed by about 80 mcg/day.

22. The method of claim 12, wherein the incretin mimetic comprises a GLP-1 peptide, a peptide analog thereof, or a peptide derivative thereof.

23. The method of claim 12, wherein the incretin mimetic is selected from the group consisting of lixisenatide, liraglutide, albiglutide, and taspoglutide.

24. The method of claim 12, wherein the vehicle formulation comprises a solvent and a polymer.

25. The method of claim 24, wherein the solvent is selected from the group consisting of benzyl benzoate, lauryl lactate, and lauryl alcohol.

26. The method of claim 24, wherein the polymer is a polyvinvylpyrrolidone.

27. The method of claim 1, wherein the subject is a human.

11. The method of 10, wherein the reservoir comprises titanium or a titanium alloy.

28. A method of treating a disease or condition in a subject in need of treatment, comprising

providing continuous delivery of a drug from an osmotic delivery device, wherein substantial steady-state delivery of the drug at therapeutic concentrations is achieved within a time period of about 7 days or less after implantation of the osmotic delivery device in the subject and the substantial steady-state delivery of the drug from the osmotic delivery device is continuous over an administration period of at least about 3 months, wherein the drug has a half-life.

29. The method of claim 28, further comprising the capability to terminate the continuous delivery such that the concentration of the drug is substantially undetectable in a blood sample from the subject within about 6 half-lives or less of the drug after termination of continuous delivery.

30. The method of claim 29, wherein termination of continuous delivery is removal of the osmotic delivery device from the subject.

31. The method of claim 28, wherein the method further comprises a first continuous administration period of the drug at a dose/day that is followed by a second continuous administration period providing a dose escalation of the drug to a second dose/day, wherein the second dose/day is greater than the first dose/day.

32. The method of claim 31, wherein the first dose/day is delivered by a first osmotic delivery device and the second dose/day is delivered by a second osmotic delivery device, and delivery of the drug from at least the first or the second osmotic delivery device is continuous over the administration period of at least about 3 months.

33. The method of claim 28, further comprising the proviso that the disease or condition is not prostate cancer.

34. The method of claim 28, wherein the osmotic delivery device comprises a drug formulation, and the drug formulation comprises the drug and a vehicle formulation.

35. The method of claim 28, wherein the osmotic delivery device comprises a suspension formulation, and the suspension formulation comprises

a particle formulation comprising the drug, and

a vehicle formulation.

36. The method of claim 35, wherein the drug comprises a polypeptide.

37. The method of claim 36, wherein the polypeptide is selected from the group consisting of recombinant antibodies, antibody fragments, humanized antibodies, single chain antibodies, monoclonal antibodies, and avimers.

38. The method of claim 36, wherein the polypeptide is selected from the group consisting of human growth hormone, epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor, and nerve growth factor.

39. The method of claim 28, wherein the subject is a human.