Rapid establishment and/or termination of substantial steady-state drug delivery
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.
1. A drug dosage form comprising a first implantable osmotic delivery device and a second implantable osmotic delivery device separately in two kits, wherein:
the first implantable osmotic delivery device comprises exenatide, provides continuous administration of 20 mcg/day exenatide, and is configured for administration during a first dosing period;
the second implantable osmotic delivery device comprises exenatide, provides continuous administration from 40 mcg/day to 80 mcg/day exenatide, and is configured for administration during a second dosing period; and
the drug dosage form is configured to provide a dose escalation of exenatide to a human subject upon implantation of the first osmotic delivery device in the human subject, removal of the first osmotic delivery device from the human subject, and implantation of the second osmotic delivery device in the human subject.
2. The drug dosage form according to claim 1 , wherein the second implantable osmotic delivery device provides continuous administration of 40 mcg/day exenatide.
3. The drug dosage form according to claim 1 , wherein the second implantable osmotic delivery device provides continuous administration of 60 mcg/day exenatide.
4. The drug dosage form according to claim 1 , wherein the second implantable osmotic delivery device provides continuous administration of 80 mcg/day exenatide.
5. The drug dosage form according to claim 1 , wherein each of the first and second implantable osmotic delivery devices comprises a suspension formulation of the exenatide.
6. The drug dosage form according to claim 5 , wherein the suspension formulation comprises a particle formulation of the exenatide.
7. The drug dosage form according to claim 5 , wherein the suspension formulation comprises a particle formulation of the exenatide 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.
8. The drug dosage form according to claim 1 , wherein each of the first and second implantable osmotic delivery devices is further configured to provide substantial steady-state delivery of the exenatide that is continuous for at least about three months to about one year.
9. The drug dosage form according to claim 1 , wherein each of the first and second implantable osmotic delivery devices is further configured to provide substantial steady-state delivery of exenatide that is continuous for at least about three months.
10. The drug dosage form according to claim 1 , wherein the first implantable osmotic delivery device provides continuous administration of 20 mcg/day of exenatide for about three months.
11. The drug dosage form according to claim 1 , wherein the first implantable osmotic delivery device provides continuous administration of 20 mcg/day of exenatide for about three months, and the second implantable osmotic delivery device provides continuous administration of 60 mcg/day of exenatide for about six months.
12. The drug dosage form according to claim 1 , wherein each of the first and second implantable osmotic delivery devices comprises a cylindrical reservoir that is capped at one end by a rate-controlled semi-permeable membrane and capped at the other end by a diffusion moderator.
13. The drug dosage form according to claim 12 , wherein each 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.
14. The drug dosage form according to claim 1 , configured for treating type 2 diabetes in the human subject.
15. The drug dosage form according to claim 1 , configured for reducing body weight in the human subject.
16. The drug dosage form according to claim 1 , configured to facilitate weight loss in the human subject.
17. The drug dosage form according to claim 1 , configured for treating obesity in the human subject.
18. The drug dosage form according to claim 1 , configured for suppressing appetite in the human subject.
19. The drug dosage form according to claim 1 , configured for reducing HbA1c plasma concentration in the human subject.
20. The drug dosage form according to claim 1 , configured for reducing LDL-C in the human subject.
21. The drug dosage form according to claim 1 , configured for reducing glucose levels in the human subject.
22. The drug dosage form according to claim 1 , configured for reducing fructosamine levels in the human subject.
23. The drug dosage form according to claim 1 , configured for reducing systolic blood pressure in the human subject.
24. The drug dosage form according to claim 1 , wherein each of the first and second implantable osmotic delivery devices is configured to provide substantial steady-state delivery of exenatide at a therapeutic concentration within about 5 days after each implantation of each osmotic delivery device.