DEVICES AND METHODS FOR DELIVERING OPIOID ANTAGONISTS INCLUDING FORMULATIONS FOR NALOXONE

• US 20160015895A1
• Filed: 07/18/2014
• Published: 01/21/2016
• Est. Priority Date: 07/18/2014
• Status: Active Grant

• Current Assignee: Kaleo, Inc.
• Original Assignee: Kaleo, Inc.
• Inventors: Blondino, Frank E., Edwards, Eric S., Edwards, Evan T., Kelley, Glen L., Meyers, Paul F.
• Granted Patent: US 9,517,307 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61M 11/02 operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised sprayers for horticulture A01G, A01H; killing insects A01M; air humidifying by nozzles F24F6/14, F24F6/18; cooling by spraying F28B, F28C
• CPC Class Codes: A61M 5/2033 Spring-loaded one-shot injectors with or without automatic needle insertion multishot dosing syringes A61M5/31525, needle insertion only A61M5/3287
• CPC Class Codes: A61M 5/2053 Media being expelled from injector by pressurised fluid or vacuum for infusion A61M5/145, A61M5/155
• CPC Class Codes: A61M 5/3234 Fully automatic needle retraction, i.e. in which triggering of the needle does not require a deliberate action by the user
• CPC Class Codes: A61M 5/3287 Accessories for bringing the needle into the body; Automatic needle insertion A61M5/20, A61M5/31525 take precedence
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An apparatus includes a container, a needle, and an actuation assembly. The container contains a dose of a naloxone composition having a delivered volume of at least about 0.34 mL. The actuation assembly includes an energy storage member that produces a force on a movable member to move the needle and to deliver the dose of the naloxone composition. The 90% confidence interval of at least one of the relative mean maximum naloxone plasma concentration after dose delivery into the body (C_max), time to reach the maximum naloxone plasma concentration (T_max), area under the plasma concentration-time curve from pre-dose (time 0) extrapolated to infinity (AUC_0-∞), or area under the plasma concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (T_last) (AUC_0-t) of the delivered dose to a delivered dose of a corresponding naloxone composition delivered via a manually-actuated syringe is within 80% to 125%.

Claims

1. An apparatus, comprising:

a housing;

a medicament container disposed within the housing, the medicament container containing a dose of a naloxone composition, the dose having a delivered volume of at least about 0.34 ml;

a needle configured to move between a first needle position, in which the needle is disposed within the housing, and a second needle position, in which a portion of the needle extends from the housing, the needle configured to be placed in fluid communication with the medicament container when the needle is in the second needle position; and

an actuation assembly including an energy storage member and a movable member, the energy storage member configured to produce a force on the movable member to move the needle from the first needle position to the second needle position and deliver the dose of the naloxone composition from the medicament container via the needle,

when actuated, the actuation assembly delivers the dose of the naloxone composition into a body in less than about 0.5 seconds and such that the 90% confidence interval of at least one of the relative mean maximum naloxone plasma concentration after the dose is delivered into the body (C_max), time to reach the maximum naloxone plasma concentration (T_max), area under the plasma concentration-time curve from pre-dose (time

     0) extrapolated to infinity (AUC_0-∞

), or area under the plasma concentration-time curve from pre-dose (time

     0) to the time of the last quantifiable concentration (T_last) (AUC_0-t) of the delivered dose to a delivered dose of a corresponding naloxone composition delivered via a manually-actuated syringe is within 80% to 125%.

3. The apparatus of claim 1, wherein the force delivered by the actuation assembly on the movable member decreases during delivery of the dose from a start force to an end force.

4. The apparatus of claim 1, wherein the force delivered by the actuation assembly on the movable member decreases during delivery of the dose from a start force to an end force, the start force being between about between about 30 pounds and about 38 pounds, the end force being between about 23 pounds and about 31 pounds.

5. The apparatus of claim 1, wherein when the actuation assembly is actuated, a pressure produced within the medicament container by the movable member decreases during delivery of the dose from a start pressure to an end pressure, the start pressure being between about between about 525 pounds per square inch and about 670 pounds per square inch, the end pressure being between about 400 pounds per square inch and about 545 pounds per square inch.

6. The apparatus of claim 1, further comprising:

a retraction mechanism configured to produce a retraction force to move the needle from the second needle position towards the first needle position after delivery of the dose.

7. The apparatus of claim 1, further comprising:

a retraction mechanism configured to produce a retraction force of about 5 pounds to move the needle from the second needle position towards the first needle position after delivery of the dose.

8. The apparatus of claim 1, further comprising:

a retraction spring configured to urge the needle towards the first needle position; and

a release member, the movable member configured to interface with a release member after delivery of the dose to release the force from the movable member, the actuation assembly and the release member configured such that about 0.4 ml of the naloxone composition is delivered before the needle begins movement from the second needle position towards the first needle position.

9. The apparatus of claim 1, wherein the delivered volume is about 0.4 ml.

10. The apparatus of claim 1, wherein the delivered volume is between about 0.34 ml and about 0.46 ml.

11. The apparatus of claim 1, wherein the delivered volume is between about 0.34 ml and about 2 ml.

12. The apparatus of claim 1, wherein the amount of the dose is about 0.4 mg.

13. The apparatus of claim 1, wherein the amount of the dose is between about 0.4 mg and about 1 mg.

14. The apparatus of claim 1, wherein the amount of the dose is between about 0.4 mg and about 2 mg.

15. The apparatus of claim 1, wherein the amount of the dose is between about 0.4 mg and about 10 mg.

16. The apparatus of claim 1, wherein the energy storage member is a compressed gas container having an initial container pressure of about 1100 pounds per square inch.

26. The apparatus of claim 1, wherein when actuated, the actuation assembly delivers the dose of the naloxone composition into a body such that the 90% confidence interval of the relative mean C_max of the delivered dose to a delivered dose of a corresponding naloxone composition delivered via a manually-actuated syringe is within 100% to 125%.

31. The apparatus of claim 1, wherein the needle has an exposed needle length of about 0.5 inches when the needle is in the second needle position.

2. (canceled)

17-22. -22. (canceled)

23. A method, comprising:

placing a medicament injector against a body, the medicament injector including;

a housing;

a medicament container disposed within the housing, the medicament container containing a dose of a naloxone composition, the dose having a delivered volume of at least about 0.34 ml;

a needle configured to move between a first needle position and a second needle position, a portion of the needle extending from the housing when the needle is in the second needle position, the needle configured to be placed in fluid communication with the medicament container when the needle is in the second needle position; and

an actuation assembly including an energy storage member and a movable member; and

actuating the medicament injector such that the energy storage member produces a force on the movable member to move the needle from the first needle position to the second needle position and deliver the dose of the naloxone composition from the medicament container via the needle into the body in less than about 0.5 seconds and in a manner such that the 90% confidence interval of at least one of the relative mean maximum naloxone plasma concentration after the dose is delivered into the body (C_max), time to reach the maximum naloxone plasma concentration (T_max), area under the plasma concentration-time curve from pre-dose (time

     0) extrapolated to infinity (AUC_0-∞

), or area under the plasma concentration-time curve from pre-dose (time

     0) to the time of the last quantifiable concentration (T_last) (AUC_0-t) of the delivered dose to a delivered dose of a corresponding naloxone composition delivered via a manually-actuated syringe is within 80% to 125%.

24. The method of claim 23, wherein the actuating includes pressing a distal end portion of the housing against the body.

32. The apparatus of claim 23, wherein the portion of the needle has a length of about 0.5 inches.

25. (canceled)

27-30. -30. (canceled)