Rapid establishment and/or termination of substantial steady-state drug delivery
Inventors
Alessi, Thomas R. • Luskey, Kenneth
Assignees
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Publication Number
US-12042557-B2
Publication Date
2024-07-23
Expiration Date
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.
Core Innovation
The invention relates to a drug dosage form that uses implanted osmotic delivery to deliver incretin mimetics, including exenatide, in a continuous manner. Implantation rapidly establishes substantial steady-state therapeutic drug concentrations in the blood and maintains continuous delivery for an extended period.
The disclosed delivery concept emphasizes that the implanted device can be stopped by removing the device, which causes the blood drug concentration to become substantially undetectable within a period defined by drug half-lives. The background problem addressed is the need for pharmaceutical treatment in which exenatide can reach substantial steady-state therapeutic concentrations rapidly, provide continuous administration for months, and then be rapidly terminated when desired.
A key implementation described is a drug dosage form that includes a first and a second implantable osmotic delivery device, provided separately in two kits. The first implantable osmotic delivery device administers exenatide continuously during a first dosing period, after which the first device is removed and the second device is implanted for a second dosing period, providing a dose escalation of exenatide to a human subject.
The osmotic delivery device architecture described includes a reservoir, a rate-controlled semi-permeable membrane, and an osmotic engine with a piston, together with a diffusion moderator and an exenatide suspension formulation. The description associates this architecture with reaching substantial steady-state concentrations within about 5 days and maintaining delivery over months.
Claims Coverage
The partial content identifies one independent claim. It includes four inventive features directed to escalation dosing of exenatide using two separately packaged implantable osmotic delivery devices, continuous administration during first and second dosing periods, and dose escalation triggered by implantation, removal, and re-implantation.
Two implantable osmotic delivery devices in separate kits for exenatide escalation
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 and second devices each comprise exenatide and are used to provide a dose escalation upon sequential implantation and replacement.
First device for a first dosing period with continuous exenatide administration
The first implantable osmotic delivery device provides continuous administration of exenatide and is configured for administration during a first dosing period.
Second device for a second dosing period with continuous exenatide administration
The second implantable osmotic delivery device provides continuous administration of exenatide and is configured for administration during a second dosing period.
Escalation configured by removing the first device and implanting the second device
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, removal of the first osmotic delivery device, and implantation of the second osmotic delivery device.
Across the identified independent claim, the core coverage is the escalation of exenatide dosing in a human subject using two separately packaged implantable osmotic delivery devices that provide continuous administration during first and second dosing periods, with escalation achieved by sequential implantation and removal of the devices.
Stated Advantages
Rapid establishment of substantial steady-state therapeutic drug concentrations after implantation.
Continuous delivery for an administration period of months.
Rapid termination by removing the implantable device, with blood drug concentration becoming substantially undetectable within a defined period.
Reduced gastrointestinal adverse events such as nausea compared with injection.
Improved quality of life (DM-SAT).
100% compliance due to elimination of self-injection.
Documented Applications
Pharmaceutical treatment in humans with type 2 diabetes mellitus, including outcomes such as fasting plasma glucose reduction and improvements in HbA1c and fructosamine, and weight loss.
Treatment in which drug delivery is compared with injection, including reduction of gastrointestinal adverse events such as nausea/vomiting and assessment of quality of life (DM-SAT).
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