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

• US 10,231,923 B2
• Filed: 08/22/2016
• Issued: 03/19/2019
• 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
• Primary Examiner(s): Tran, Susan T
• Application Number:
  US15/242,732
• Publication Number:
  US 20160354305A1
• Time in Patent Office: 939 Days
• Field of Search: None
• 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 for treating type 2 diabetes mellitus in a human subject, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device, wherein

(i) continuous administration comprises a first continuous administration period of the incretin mimetic at a first mcg/day dose, followed by a second continuous administration period of the incretin mimetic at a second mcg/day dose, wherein the second mcg/day dose is greater than the first mcg/day dose,

(ii) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(iii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months,

(iv) the first mcg/day dose followed by the second mcg/day dose is about 20 mcg/day followed by about 60 mcg/day, and

(v) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.

18. The method according to claim 1, wherein the human subject is on metformin-only background treatment.

19. The method according to claim 1, wherein the substantial steady-state delivery of the incretin mimetic from the at least one osmotic delivery device is continuous over at least one administration period of about three months to about one year.

20. The method according to claim 1, further comprising providing a significant decrease in the subject'"'"'s fasting plasma glucose concentration in about 7 days or less after implantation of the at least one osmotic delivery device in the human subject, relative to the human subject'"'"'s fasting plasma glucose concentration before implantation of the at least one osmotic delivery device.

21. The method according to claim 1, comprising providing a significant decrease in the subject'"'"'s HbA1c plasma concentration in about 7 days or less after implantation of the at least one osmotic delivery device in the human subject, relative to the human subject'"'"'s HbA1c plasma concentration before implantation of the at least one osmotic delivery device.

22. The method according to claim 1, further comprising the capability to terminate the continuous administration such that the concentration of incretin mimetic is substantially undetectable in a blood sample from the subject in less than about 72 hours after termination of continuous administration.

23. The method according to claim 22, wherein termination of continuous administration is removal of the at least one osmotic delivery device from the subject.

24. The method according to claim 23, wherein the incretin mimetic is detected by a radioimmunoassay.

25. The method according to claim 1, wherein the first mcg/day dose is administered by a first osmotic delivery device and the second mcg/day dose is administered by a second osmotic delivery device.

26. The method according to claim 1, wherein the method comprises at least one more continuous administration period providing a dose escalation of the incretin mimetic to a third mcg/day dose that is higher relative to the second mcg/day dose.

27. The method according to claim 1, wherein the first mcg/day dose for about 3 months is followed by the second mcg/day dose for about 6 months.

28. The method according to claim 1, wherein substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 3 days after each implantation of an osmotic delivery device.

29. The method according to claim 1, wherein the incretin mimetic comprises an exenatide peptide, exenatide peptide analog, exenatide peptide derivative, GLP-1 peptide, GLP-1 peptide analog, or GLP-1 peptide derivative.

30. The method according to claim 29, wherein the incretin mimetic comprises an exenatide peptide having the amino acid sequence of exendin-4.

31. The method according to 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

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

32. The method according to claim 31, wherein the reservoir comprises titanium or a titanium alloy.

33. The method according to claim 31, wherein the suspension formulation is flowable, the suspension formulation comprising a particle formulation comprising exenatide peptide, and a vehicle formulation, wherein the vehicle formulation comprises a solvent and a polymer, wherein the solvent is selected from the group consisting of benzyl benzoate, lauryl lactate, and lauryl alcohol, and the polymer is polyvinylpyrrolidone.

34. The method according to claim 1, wherein the human subject has tolerized to the incretin mimetic following the first administration period at the first mcg/day dose.

2. A method for reducing body weight, treating obesity, suppressing appetite or facilitating weight loss in a human subject, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device, wherein

(i) continuous administration comprises a first continuous administration period of the incretin mimetic at a first mcg/day dose, followed by a second continuous administration period of the incretin mimetic at a second mcg/day dose, wherein the second mcg/day dose is greater than the first mcg/day dose,

(ii) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(iii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months,

(iv) the first mcg/day dose followed by the second mcg/day dose is about 20 mcg/day followed by about 60 mcg/day, and

(v) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.

9. The method according to claim 2, for reducing body weight in a human subject.

10. The method according to claim 2, to facilitate weight loss in a human subject.

11. The method according to claim 2, for treating obesity in a human subject.

12. The method according to claim 2, for suppressing appetite in a human subject.

3. A method for reducing HbA1c plasma concentration, reducing systolic blood pressure, reducing LDL-C, reducing glucose levels, or reducing fructosamine levels in a human subject, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device, wherein

(i) continuous administration comprises a first continuous administration period of the incretin mimetic at a first mcg/day dose, followed by a second continuous administration period of the incretin mimetic at a second mcg/day dose, wherein the second mcg/day dose is greater than the first mcg/day dose,

(ii) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(iii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months,

(iv) the first mcg/day dose followed by the second mcg/day dose is about 20 mcg/day followed by about 60 mcg/day, and

(v) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.

13. The method according to claim 3, for reducing HbA1c plasma concentration in a human subject.

14. The method according to claim 3, for reducing LDL-C in a human subject.

15. The method according to claim 3, for reducing glucose levels in a human subject.

16. The method according to claim 3, for reducing fructosamine levels in a human subject.

17. The method according to claim 3, for reducing systolic blood pressure in a human subject.

4. A method for mitigating nausea in a human subject, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device, wherein

(i) continuous administration comprises a first continuous administration period of the incretin mimetic at a first mcg/day dose, followed by a second continuous administration period of the incretin mimetic at a second mcg/day dose, wherein the second mcg/day dose is greater than the first mcg/day dose,

(ii) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(iii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months,

(iv) the first mcg/day dose followed by the second mcg/day dose is about 20 mcg/day followed by about 60 mcg/day, and

(v) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.

5. A method for treating type 2 diabetes mellitus in a human subject who has been administered an incretin mimetic during a first administration period at a first mcg/day dose, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device during a second continuous administration period at a second mcg/day dose that is 60 mcg/day, wherein

(i) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(ii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months, and

(iii) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.

6. A method for reducing body weight, treating obesity, suppressing appetite or to facilitate weight loss in a human subject who has been administered an incretin mimetic during a first administration period at a first mcg/day dose, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device during a second continuous administration period at a second mcg/day dose that is 60 mcg/day, wherein

(i) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(ii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months, and

(iii) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.

7. A method for reducing HbA1c plasma concentration, reducing LDL-C, reducing systolic blood pressure, reducing glucose levels, or reducing fructosamine levels in a human subject who has been administered an incretin mimetic during a first administration period at a first mcg/day dose, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device during a second continuous administration period at a second mcg/day dose that is 60 mcg/day, wherein

(i) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(ii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months, and

(iii) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.

8. A method for mitigating nausea in a human subject who has been administered an incretin mimetic during a first administration period at a first mcg/day dose, the method comprising:

implanting in the human subject at least one osmotic delivery device comprising an incretin mimetic to provide continuous administration of the incretin mimetic from the at least one osmotic delivery device during a second continuous administration period at a second mcg/day dose that is 60 mcg/day, wherein

(i) substantial steady-state delivery of the incretin mimetic at a therapeutic concentration is achieved within about 5 days after each implantation of an osmotic delivery device,

(ii) substantial steady-state delivery of the incretin mimetic is continuous for at least about 3 months, and

(iii) the osmotic delivery device comprises a cylindrical reservoir that is capped at one end by a controlled-rate, semi-permeable membrane and capped at the other end by a diffusion moderator.