Infusion delivery devices and methods

Abstract

Devices that include multi-reservoir infusion devices and systems for dispensing compositions for the treatment of subjects with an amylin agonist (e.g., the amylin agonist analog, pramlintide), wherein amylin agonists are administered in certain differential bolus and basal ratios to an administered insulin, as well as methods, compositions, and kits and articles of manufacture comprising said compositions for use in the treatment of responsive patients with an amylin and an insulin in ratios thereof that are distinct for bolus and basal administration.

What is claimed is: 
     
         1 . A medical infusion pump system for delivering an insulin and an amylin agonist analog to a patient, said system comprising a user interface, an insulin drug reservoir, an amylin agonist analog drug reservoir, and independent pumping mechanisms for said drug reservoirs, wherein said pumping mechanisms can be regulated by the patient and/or one or more computer algorithms via a processor that (a) sets the basal and bolus rates of insulin infusion according to individual patient needs and (b) calculates the basal and bolus rates of amylin agonist analog infusion in ratios to said basal and bolus insulin infusion rates, wherein the amylin agonist analog/insulin basal ratio is different from and higher than the amylin agonist analog/insulin bolus ratio. 
     
     
         2 . A medical infusion pump system according to  claim 1 , wherein said computer algorithm(s) is/are configured to provide basal and bolus dosing of said insulin and said amylin agonist analog that will stabilize plasma glucose levels in said patient. 
     
     
         3 . A medical infusion pump system according to  claim 1 , wherein said computer algorithm(s) is/are configured to provide basal and bolus dosing of said insulin and said amylin agonist analog that will improve the glucagon counter-regulatory response in said patient. 
     
     
         4 . A medical infusion pump system according to  claim 1  that is programmable and the molar ratio of basal amylin agonist analog to basal insulin is from about 1:14 to about 1:6 or 1:7; and the ratio of bolus amylin agonist analog to bolus insulin is about 1:50 to about 1:20. 
     
     
         5 . A medical infusion pump system according to  claim 1 , wherein the user interface is a touchscreen, a smart phone, or a smart watch or other wearable device. 
     
     
         6 . A medical infusion pump system according to  claim 1 , wherein the processor is programmed to calculate a basal amount of an amylin agonist analog and to deliver said amylin agonist analog from said drug reservoir at a basal rate by comparing the pharmacokinetics of said amylin agonist analog and said insulin in order to maintain a basal plasma level of said amylin agonist analog that is from about 7% to about 15% or from about 5% to 22% of the basal plasma levels of said insulin. 
     
     
         7 . A medical infusion pump system according to  claim 1 , wherein the processor is programmed to calculate and deliver a bolus amount of an amylin agonist analog by comparing the pharmacokinetics of said amylin analog and said insulin in order to deliver a bolus of said amylin agonist analog to yield a plasma level that is from about 2% to 5% or from about 2% to about 7% of the plasma level resulting from said bolus administration of said insulin. 
     
     
         8 . A medical infusion pump system according to  claim 1 , wherein the processor is programmed to calculate the basal amount of said amylin agonist analog to be delivered by further evaluating one or more dosing parameters selected from the group consisting of mean or median values of amylin agonist analog/insulin ratios generated from clinical studies, and ranges thereof; subject age; subject body mass index; expected levels of glucagon secretion; subject exercise; and, subject diet. 
     
     
         9 . A medical infusion pump system according to  claim 1 , wherein the processor is programmed to receive data specifying a bolus amount, the duration of administration of the bolus amount, the portion of the bolus amount to be delivered immediately upon executing a deliver command and a remainder of the bolus amount to deliver over the duration upon executing a deliver command, and execute the deliver command thereby controlling the drug pump to deliver the bolus. 
     
     
         10 . A medical infusion pump system according to  claim 1 , wherein the amylin agonist analog is pramlintide, and the pump is programmed (a) to administer pramlintide to said subject in an amount and frequency to provide a basal pramlintide level over a 24-hour period that is equal to about 15% of said basal insulin level, and (b) to administer a mealtime bolus of pramlintide one or more times per day in an amount and frequency to provide a mealtime bolus of pramlintide to said subject that is equal to about 5% of a mealtime bolus amount of said insulin administered to said subject. 
     
     
         11 . A medical infusion pump system selected from the group consisting of:
 a. a programmable medical infusion pump system having a user interface, said pump comprising a drug reservoir, a drug pump, a data input device, and a processor in data communication with a user interface and arranged to control the drug pump, wherein the processor is programmed to deliver an amylin agonist from said drug reservoir at a differential basal rate and a bolus rate to a user by prompting the user to select a basal or bolus insulin infusion rate or by referencing a preselected basal or bolus insulin infusion rate, calculating a delivery rate for said amylin agonist based on a predetermined ratio of basal or bolus amylin agonist to said basal or bolus insulin over a predetermined period of time, and controlling the drug pump to deliver said amylin agonist from said drug reservoir at a delivery rate substantially equal to the calculated basal or bolus rate during the period of time; and   b. a programmable medical infusion pump system having a touchscreen, said pump comprising a drug pump, a data input device, and a processor in data communication with a touchscreen and arranged to control the drug pump, wherein (a) the processor is programmed to deliver an amylin agonist at a basal rate to a user by prompting the user to select a basal insulin infusion rate or by referencing a preselected basal insulin infusion rate, calculating a delivery rate for said amylin agonist based on a predetermined ratio of basal amylin agonist to said basal insulin over a predetermined period of time, (b) the processor is programmed to deliver a mealtime bolus amount of an amylin agonist to a user by prompting the user to select a mealtime bolus amount of an insulin or by referencing a preselected mealtime insulin bolus amount and infusion rate, calculating a delivery rate for said amylin agonist based on a predetermined ratio of said mealtime amylin agonist bolus to said mealtime insulin bolus over a predetermined period of time, and (c) the processor controls the drug pump to deliver said amylin agonist in amounts and at delivery rates substantially equal to the calculated basal amount and rate and the calculated mealtime bolus amount over said predetermined periods of time;   c. a programmable medical infusion pump system having a keypad or touchscreen, said pump comprising an amylin agonist drug reservoir, an insulin drug reservoir, one or more drug pumps, a data input device, and a processor in data communication with a keypad or touchscreen and arranged to control the drug pump(s), wherein the processor is programmed (a) to deliver a basal insulin amount from said insulin drug reservoir, (b) to deliver an amylin agonist from said amylin agonist drug reservoir at a basal rate to a user by prompting the user to select a basal insulin infusion rate or by referencing a preselected basal insulin infusion rate, calculating a delivery rate for said amylin agonist based on a predetermined ratio of basal amylin agonist to said basal insulin over a predetermined period of time, and (c) to control a drug pump to deliver said amylin agonist from said drug reservoir at a delivery rate substantially equal to the calculated basal rate during the period of time   d. a programmable medical infusion pump system having a keypad or touchscreen, said pump comprising an amylin agonist drug reservoir, an insulin drug reservoir, one or more drug pumps, a data input device, and a processor in data communication with a keypad or touchscreen and arranged to control the drug pump, wherein the processor is programmed to (a) deliver a mealtime bolus amount of an insulin from said insulin drug reservoir, (b) to deliver a mealtime bolus amount of an amylin agonist from said amylin agonist drug reservoir to a user by prompting the user to select a mealtime bolus amount of an insulin or by referencing a preselected mealtime insulin bolus amount and infusion rate, calculating a delivery rate for said amylin agonist based on a predetermined ratio of said mealtime amylin agonist bolus to said mealtime insulin bolus over a predetermined period of time, and controlling the drug pump to deliver said amylin agonist from said drug reservoir at a delivery rate substantially equal to the calculated mealtime bolus during the period of time; and   e. a medical infusion pump system containing a pharmaceutical formulation comprising an amylin agonist and a pharmaceutical formulation comprising an insulin, said pump being programmed to administer said amylin agonist and said insulin to a subject in an amount and frequency to provide a basal level of said insulin and to provide a basal plasma level of said amylin agonist over a 24-hour period that is equal to from between about 7% to about 15% of said basal level of insulin, and, optionally, programmed to administer a mealtime bolus of insulin and to administer a mealtime bolus of an amylin agonist wherein said amylin agonist is administered one or more times per day in an amount and frequency to provide a mealtime bolus of said amylin agonist to said subject that is equal to from between about 2% to about 5% of a mealtime bolus amount of an insulin administered to said subject.   
     
     
         12 . A medical infusion pump system according to  claim 11 , wherein the amylin agonist is pramlintide, and the pump is programmed (a) to administer pramlintide to said subject in an amount and frequency to provide a basal pramlintide level over a 24-hour period that is equal to about 15% of said basal insulin level, and (b) to administer a mealtime bolus of pramlintide one or more times per day in an amount and frequency to provide a mealtime bolus of pramlintide to said subject that is equal to about 5% of a mealtime bolus amount of said insulin administered to said subject. 
     
     
         13 . A medical infusion pump system according to  claim 11  that is programmable and further comprises at least one of the following:
 a. the molar ratio of basal amylin agonist to basal insulin is about 1:6 or 1:7; 
 b. the amylin agonist is pramlintide, the insulin is a short-acting insulin, and the ratio of basal pramlintide to basal insulin infusion is from about 1:14 to about 1:6 or 1:7; 
 c. the drug pump is configured to administer said amylin agonist from said drug reservoir by continuous subcutaneous infusion; 
 d. said user interface is a keypad or touchscreen; 
 e. the ratio of bolus amylin agonist to bolus insulin is about 1:20; 
 f. the amylin agonist is pramlintide, the insulin is a long-acting insulin, and the ratio of basal pramlintide to basal insulin infusion is from about 1:50 to about 1:20; and 
 g. a user interface that is a smart phone or smart watch; 
 h. the processor is programmed to calculate a basal amount of an amylin agonist and to deliver said amylin agonist from said drug reservoir at a basal rate by comparing the pharmacokinetics of said amylin agonist and said insulin in order to maintain a basal plasma level of said amylin agonist that is from about 7% to about 15% or from about 5% to 22% of the basal plasma levels of said insulin; 
 i. the processor is programmed to calculate and deliver a bolus amount of an amylin agonist by comparing the pharmacokinetics of said amylin agonist and said insulin in order to deliver a bolus of said amylin agonist to yield a plasma level that is from about 2% to 5% or from about 2% to about 7% of the plasma level resulting from said bolus administration of said insulin; 
 j. processor is programmed to calculate the basal amount of said amylin agonist to be delivered by further evaluating one or more dosing parameters selected from the group consisting of mean or median values of amylin agonist/insulin ratios generated from clinical studies, and ranges thereof; subject age; subject body mass index; expected levels of glucagon secretion; subject exercise; and, subject diet; and 
 k. the processor is programmed to receive data specifying a bolus amount, the duration of administration of the bolus amount, the portion of the bolus amount to be delivered immediately upon executing a deliver command and a remainder of the bolus amount to deliver over the duration upon executing a deliver command, and execute the deliver command thereby controlling the drug pump to deliver the bolus. 
 
     
     
         14 . A method selected from the group consisting of:
 a. for treating an insulin-using subject with an amylin agonist, comprising administering an amylin agonist to said subject in an amount and frequency to provide a basal plasma level of said amylin agonist over a 24-hour period that is equal to from between about 7% to about 15% of a basal plasma level of an insulin administered to said subject, and administering an amylin agonist one or more times per day in an amount and frequency to provide a mealtime bolus of said amylin agonist that is equal to from between about 2% to about 5% of a mealtime bolus amount of an insulin administered to said subject;   b. a method of treating hyperglycemia, comprising (a) administering an amylin agonist in an amount and frequency to provide a basal plasma level of said amylin agonist over a 24-hour period that is equal to from between about 7% to about 15% of a basal level of an insulin administered to said subject, and (b) administering an amylin agonist one or more times per day in an amount and frequency to provide a mealtime bolus of said amylin agonist that is equal to from between about 2% to about 5% of a mealtime bolus amount of an insulin administered to said subject;   
     
     
         15 . A method according to  claim 14  that further comprises at least one of the following:
 a. the amylin agonist is a derivative of amylin; 
 b. the amylin agonist is an agonist analog of amylin; 
 c. the amylin agonist is pramlintide; 
 d. the amylin agonist is administered in conjunction with insulin; 
 e. the amylin agonist administered to provide a basal level of amylin agonist and the amylin agonist administered as a mealtime bolus of said amylin agonist is pramlintide; 
 f. the insulin administered with the bolus amylin agonist is a short-acting insulin; 
 g. the insulin administered with the basal amylin agonist is a long-acting insulin; 
 h. the insulin administered to provide a basal level of insulin and the insulin administered as a mealtime bolus is a short-acting insulin and a long-acting insulin, respectively; 
 i. the amylin agonist is administered by injection; 
 j. the amylin agonist is administered by infusion; 
 k. the amylin agonist is administered by infusion from a medical infusion pump system; 
 l. the amylin agonist is administered by subcutaneous continuous infusion; 
 m. the amylin agonist is administered by subcutaneous infusion; 
 n. the amylin agonist and the insulin are administered by subcutaneous continuous infusion; 
 o. the amylin agonist and the insulin are administered by subcutaneous infusion; 
 p. the amylin agonist and the insulin are administered by subcutaneous continuous infusion from a programmable medical infusion pump system; 
 q. the bolus amylin agonist and the bolus insulin are administered by subcutaneous infusion from a programmable medical infusion pump system; 
 r. the subject is a human; 
 s. the subject has Type 1 diabetes; 
 t. the subject has Type 2 diabetes 
 u. the amylin agonist and/or the insulin is administered by a patch pump. 
 
     
     
         16 . An article of manufacture selected from the group consisting of:
 a. a pharmaceutical composition for administration to a subject, comprising a basal blend of an insulin and an amylin agonist, said amylin agonist and said insulin being present in a ratio ranging from about 1:14 to about 1:6 or 1:7;   b. a pharmaceutical composition for administration to a subject, comprising a basal blend of an insulin and an amylin agonist, wherein said amylin agonist and said insulin are present in a ratio of about 1:6 or 1:7;   c. a pharmaceutical composition for administration to a subject, comprising a basal blend of an insulin and an amylin agonist wherein said amylin agonist is pramlintide and said insulin is a long-acting insulin;   d. a pharmaceutical composition for administration to a subject comprising a bolus blend of an insulin and an amylin agonist, said amylin agonist and said insulin being present in a ratio ranging from about 1:50 to about 1:20;   e. a pharmaceutical composition for administration to a subject comprising a bolus blend of an insulin and an amylin agonist, wherein said amylin agonist and said insulin are present in a ratio of about 1:20;   f. a pharmaceutical composition for administration to a subject comprising a bolus blend of an insulin and an amylin agonist, wherein said amylin agonist is pramlintide and said insulin is a short-acting insulin; and   g. a commercial package containing a pharmaceutical formulation containing an amylin agonist for parenteral administration to an insulin-using subject, said package comprising instructions for administering said amylin agonist in an amount and frequency to provide a basal plasma level of said amylin agonist over a 24-hour period that is equal to from between about 7% to about 15% of a basal level of an insulin to be administered to said subject.   
     
     
         17 . An article of manufacture according to  claim 16  that is a commercial package, wherein the commercial package further comprising at least one of the following:
 a. instructions for administering said amylin agonist one or more times per day in an amount and frequency to provide a mealtime bolus of said amylin agonist that is equal to from between about 2% to about 5% of a mealtime bolus amount of an insulin to be administered to said subject; 
 b. the amylin agonist for basal administration is a long-acting amylin agonist; 
 c. the amylin agonist for basal administration is pramlintide; 
 d. the amylin agonist for basal administration is pramlintide; 
 e. the amylin agonist for basal administration is pramlintide, and the basal plasma level of pramlintide to be administered over a 24-hour period is equal to about 15% of the basal level of an insulin to be administered to said subject over the 24-hour period; and 
 f. the amylin agonist to be administered as a mealtime bolus is pramlintide, and the amount of pramlintide to be administered as a mealtime bolus is equal to about 5% of the amount of an insulin to be administered as a mealtime bolus to said subject.