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

• US 8,298,561 B2
• Filed: 09/21/2010
• Issued: 10/30/2012
• 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.
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US12/924,175
• Publication Number:
  US 20110076317A1
• Time in Patent Office: 770 Days
• Field of Search: None
• US Class Current: 424/422
• 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 exenatide from an osmotic delivery device, the osmotic delivery device comprising

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, the osmotic engine 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 containing the osmotic engine,

a suspension formulation contained in the second chamber, the suspension formulation comprising a particle formulation and a vehicle formulation, wherein

the particle formulation comprises particles comprising exenatide in particles of less than 10 microns in diameter, and

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, the vehicle formulation having a viscosity between about 10,000 poise and about 20,000 poise at 37°

C., and

a diffusion moderator that defines a delivery orifice inserted in the second open end of the reservoir, the diffusion moderator adjacent the suspension formulation;

wherein (i) substantial steady-state delivery of the exenatide at a therapeutic concentration is achieved within a time period of 5 days or less after implantation of the osmotic delivery device in the subject, and (ii) the substantial steady-state delivery of the exenatide from the osmotic delivery device is continuous over an administration period of at least about 3 months at 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, and about 80 mcg/day.

2. The method of claim 1, wherein substantial steady-state delivery of exenatide 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 4 days or less, about 3 days or less, and about 2 days or less, and about 1 day or less.

3. The method of claim 1, wherein the substantial steady-state delivery of exenatide 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 termination of continuous delivery by removal of the osmotic delivery device from the subject 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 72 hours, less than 48 hours, less than 24 hours, and less than 12 hours.

8. The method of claim 7, wherein exenatide is detected by a radioimmunoassay.

9. The method of claim 1, wherein the reservoir comprises titanium or a titanium alloy.

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

11. The method of claim 10, wherein the first mcg/day dose is delivered by the osmotic delivery device and the second mcg/day dose is delivered by a second osmotic delivery device.

12. The method of claim 10, wherein the method further comprises at least one more continuous administration period providing a dose escalation of exenatide to a higher mcg/day dose relative to the second mcg/day dose.

13. The method of claim 10, wherein 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.

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