Devices and methods for delivering opioid antagonists including formulations for naloxone

• US 10,220,158 B2
• Filed: 12/07/2016
• Issued: 03/05/2019
• 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.
• Primary Examiner(s): Stiles, Amber
• Application Number:
  US15/371,515
• Publication Number:
  US 20170232206A1
• Time in Patent Office: 818 Days
• 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 0.34 ml;

a needle configured to be placed in fluid communication with the medicament container when an end portion of the needle is extended outside of the housing; and

an actuation assembly including an energy storage member configured to produce a force on an elastomeric member within the medicament container to 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 0.5 seconds such that a 90% confidence interval of at least one of a relative mean maximum naloxone plasma concentration after the dose is delivered into the body (C_max), a time to reach a maximum naloxone plasma concentration (T_max), an area under a plasma concentration-time curve from pre-dose (time

     0) extrapolated to infinity (AUC_0-∞

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

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

2. The apparatus of claim 1, wherein the actuation assembly is configured such that the force on the elastomeric member decreases during delivery of the dose from a start force to an end force, the start force being between about between 30 pounds and 38 pounds, the end force being between 23 pounds and 31 pounds.

3. The apparatus of claim 1, wherein the needle is configured to move between a first needle position, in which the end portion of the needle is within the housing, and a second needle position, in which the end portion of the needle extends from the housing, the apparatus further comprising:

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

a release member configured to release the force from the elastomeric member after delivery of the dose, the actuation assembly and the release member configured such that at least 0.34 ml of the naloxone composition is delivered before the needle begins movement from the second needle position towards the first needle position.

4. The apparatus of claim 1, wherein the energy storage member is any one of a spring, a compressed gas container, or a propellant container.

5. The apparatus of claim 1, wherein:

the needle is configured to move between a first needle position, in which the end portion of the needle is within the housing, and a second needle position, in which the end portion of the needle extends from the housing; and

the force moves the needle from the first needle position to the second needle position.

6. The apparatus of claim 5, wherein the needle has a length sufficient to penetrate clothing and deliver any of a subcutaneous injection or an intramuscular injection of the dose of the naloxone composition.

7. The apparatus of claim 1, wherein an amount of the dose is between 0.2 mg and 10 mg.

8. The apparatus of claim 1, wherein the naloxone composition includes 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one in a concentration of between 0.01 mg/mL and 50 mg/mL.

9. The apparatus of claim 8, wherein the concentration of the 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one is between 0.01 mg/mL and 10 mg/mL.

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

11. The apparatus of claim 1, wherein the energy storage member is any one of a compressed gas container or a propellant container that produces a pressurized gas within the housing to produce the force, the force moving the needle from a first needle position to a second needle position before the dose of the naloxone composition is delivered, the end portion of the needle being within the housing when the needle is in the first needle position, the end portion of the needle extended from the housing when the needle is in the second needle position, the apparatus further comprising:

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

a release member configured to release the pressurized gas from within the housing after delivery of the dose.

12. A method of delivering a dose of a naloxone composition, 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 the dose of the naloxone composition, the dose having a delivered volume of at least 0.34 ml;

a needle coupled to the medicament container; and

an actuation assembly including an energy storage member; and

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

     0) extrapolated to infinity (AUC_0-∞

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

     0) to a time of a 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%.

13. The method of claim 12, wherein:

the actuating the medicament injector causes the force to move the needle from a first needle position to a second needle position before the dose of the naloxone composition is delivered, the end portion of the needle being within the housing when the needle is in the first needle position, the end portion of the needle extended from the housing when the needle is in the second needle position.

14. The method of claim 13, wherein:

the energy storage member is any one of a compressed gas container or a propellant container that produces a pressurized gas within the housing to produce the force; and

the medicament injector includes a retraction spring and a release member, the retraction spring configured to urge the needle towards the first needle position, the release member releasing the pressurized gas from within the housing after delivery of the dose.

15. The method of claim 13, wherein the end portion of the needle extends from the housing by a length sufficient to penetrate clothing and deliver any of a subcutaneous injection or an intramuscular injection of the dose of the naloxone composition.

16. The method of claim 12, wherein an amount of the dose is between 0.2 mg and 10 mg.

17. The method of claim 12, wherein the naloxone composition includes 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one in a concentration of between 0.01 mg/mL and 50 mg/mL.

18. The method of claim 17, wherein the concentration of the 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one is between 0.01 mg/mL and 10 mg/mL.

19. The method of claim 12, wherein the delivered volume is between 0.34 ml and 2 ml.

20. The method of claim 12, further comprising:

storing, before the placing, the medicament injector for at least six months.

21. The method of claim 20, wherein the storing includes storing the medicament injector within a case, the method further comprising:

removing, before the placing, the medicament injector from the case.