Needle assisted jet injection administration of testosterone compositions

• US 9,950,125 B2
• Filed: 04/05/2013
• Issued: 04/24/2018
• Est. Priority Date: 04/06/2012
• Status: Active Grant

• Current Assignee: Antares Pharma Incorporated
• Original Assignee: Antares Pharma Incorporated
• Inventors: Wotton, Paul K., Dave, Kaushik J., Hayes, John W., Sadowski, Peter L., Jooste, Hermanus L., Jaffe, Jonathan
• Primary Examiner(s): BORGEEST, CHRISTINA M
• Application Number:
  US13/857,859
• Publication Number:
  US 20130303985A1
• Time in Patent Office: 1,845 Days
• Field of Search: None
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• 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 2005/2013 triggering of discharging means by contact of injector with patient body
• CPC Class Codes: A61M 2005/206 With automatic needle insertion
• CPC Class Codes: A61M 2005/2073 preventing premature release, e.g. by making use of a safety lock
• CPC Class Codes: A61M 2205/3613 by body heat
• CPC Class Codes: A61M 2205/364 by chemical reaction
• CPC Class Codes: A61M 2205/3673 thermo-electric, e.g. Peltier effect, thermocouples, semi-conductors
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 5/002 Packages specially adapted therefor, e.g. for syringes or needles, kits for diabetics needle protection, e.g. caps, A61M5/3202; for sharps A61B50/3001
• 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 5/30 Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
• CPC Class Codes: A61M 5/3153 by single stroke limiting means
• CPC Class Codes: A61M 5/3202 Devices for protection of the needle before use, e.g. caps A61M5/50 takes precedence; for infusion spikes A61M5/1626; protectors for sharps A61B50/3001
• CPC Class Codes: A61M 5/326 Fully automatic sleeve extension, i.e. in which triggering of the sleeve does not require a deliberate action by the user
• CPC Class Codes: A61M 5/425 Protruding skin to facilitate piercing, e.g. vacuum cylinders, vein immobilising means
• CPC Class Codes: A61M 5/44 having means for cooling or heating the devices or media
• CPC Class Codes: A61P 5/26 Androgens

Abstract

The present invention provides compositions and methods for treating a subject in need of treatment with testosterone, including introducing testosterone into the subject subcutaneously, intradermally, or intramuscularly, from a needle assisted jet injection device.

Claims

1. A method of administering testosterone comprising:

administering a preservative-free composition comprising a unit dose of testosterone or a pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal,

wherein after administration, a plasma level of testosterone is maintained between about 200 ng/dl and about 1800 ng/dl for a Z1 time period,

wherein the Z1 time period is at least 1 day, and

wherein administering the preservative-free composition consists of an injection via a powered injector comprising a housing, a chamber disposed within the housing and configured to receive the preservative-free composition, and a needle operatively associated with the chamber.

2. The method of claim 1, wherein the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl to about 1100 ng/dl, about 350 ng/dl to about 1050 ng/dl, about 400 ng/dl to about 1000 ng/dl, about 450 ng/dl to about 950 ng/dl, about 500 ng/dl to about 900 ng/dl, about 550 ng/dl to about 850 ng/dl, about 600 ng/dl to about 800 ng/dl, about 650 ng/dl to about 750 ng/dl, and about 675 ng/dl to about 725 ng/dl.

3. The method of claim 1, wherein the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl, about 350 ng/dl, about 400 ng/dl, about 450 ng/dl, about 500 ng/dl, about 550 ng/dl, about 600 ng/dl, about 650 ng/dl, about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, and about 1100 ng/dl.

4. The method of claim 1, wherein the plasma level of testosterone is maintained at a value selected from the group consisting of at least about 300 ng/dl, at least about 350 ng/dl, at least about 400 ng/dl, at least about 450 ng/dl, at least about 500 ng/dl, at least about 550 ng/dl, at least about 600 ng/dl, at least about 650 ng/dl, at least about 700 ng/dl, at least about 750 ng/dl, at least about 800 ng/dl, at least about 850 ng/dl, at least about 900 ng/dl, at least about 950 ng/dl, at least about 1000 ng/dl, at least about 1050 ng/dl, and at least about 1100 ng/dl.

5. The method of claim 1, wherein the Z1 time period is at least 6 days.

6. The method of claim 1, wherein the Z1 time period is at least 6.5 days.

7. The method of claim 1, wherein the Z1 time period is at least 7 days.

8. The method of claim 1, wherein the preservative-free composition comprises a liquid composition.

9. The method of claim 1, wherein administering the preservative-free composition consists of administering a single unit dose.

10. A method of administering testosterone comprising:

administering a preservative-free composition comprising a unit dose of testosterone or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal,

wherein after administration the plasma level of testosterone is maintained at a therapeutically effective level for a Z2 time period,

wherein the Z2 time period is at least 1 day, and

wherein administering the preservative-free composition consists of a single injection via a powered injector comprising a housing, a chamber disposed within the housing and configured to receive the preservative-free composition, and a needle operatively associated with the chamber.

11. The method of claim 10, wherein the preservative-free composition comprises a liquid composition.

12. A method of maintaining elevated plasma levels of testosterone in a mammal in need thereof comprising administering a preservative-free composition comprising:

a unit dose of testosterone or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal,

wherein after administration the plasma level of testosterone is maintained at a therapeutically effective level of up to about 1800 ng/dl for a Z2 time period,

wherein the Z2 time period is at least 1 day, and

wherein administering the preservative-free composition consists of a single injection via a powered injector comprising a housing, a chamber disposed within the housing and configured to receive the preservative-free composition, and a needle operatively associated with the chamber.

13. The method of claim 12, wherein the preservative-free composition comprises a liquid composition.

14. A method of administering testosterone comprising administering a preservative-free composition comprising a unit dose of testosterone or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained between about 700 ng/dl and about 1800 ng/dl for a Z2 time period, wherein the plasma level of testosterone is also maintained between about 300 ng/dl and about 1100 ng/dl for Z3 time period, after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration, and wherein administering the preservative-free composition consists of an injection via a powered injector comprising a housing, a chamber disposed within the housing and configured to receive the preservative-free composition, and a needle operatively associated with the chamber.

15. The method of claim 14, wherein after administration, the plasma level of testosterone is maintained, for a Z2 time period, at a level selected from the group consisting of about 750 ng/dl and about 1750 ng/dl, about 800 ng/dl and about 1700 ng/dl, about 850 ng/dl and about 1650 ng/dl, about 900 ng/dl and about 1600 ng/dl, about 950 ng/dl and about 1550 ng/dl, about 1000 ng/dl and about 1500 ng/dl, about 1050 ng/dl and about 1450 ng/dl, about 1100 ng/dl and about 1400 ng/dl, about 1150 ng/dl and about 1350 ng/dl, and about 1200 ng/dl and about 1300 ng/dl.

16. The method of claim 14, wherein after administration, the plasma level of testosterone is maintained, for a Z2 time period, at a level selected from the group consisting of about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, about 1100 ng/dl, about 1150 ng/dl, about 1200 ng/dl, about 1250 ng/dl, about 1300 ng/dl, about 1350 ng/dl, about 1400 ng/dl, about 1450 ng/dl, about 1500 ng/dl, about 1550 ng/dl, about 1600 ng/dl, about 1650 ng/dl, about 1700 mg/ml, about 1750 mg/ml, and about 1800 ng/dl.

17. The method of claim 14, wherein the plasma level of testosterone is maintained for a Z3 time period after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration, at a value selected from the group consisting of about 350 ng/dl to about 1050 ng/dl, about 400 ng/dl to about 1000 ng/dl, about 450 ng/dl to about 950 ng/dl, about 500 ng/dl to about 900 ng/dl, about 550 ng/dl to about 850 ng/dl, about 600 ng/dl to about 800 ng/dl, about 650 ng/dl to about 750 ng/dl, and about 675 ng/dl to about 725 ng/dl.

18. The method of claim 14, wherein the plasma level of testosterone is maintained, for Z3 time period after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration, at a value selected from the group consisting of about 300 ng/dl, about 350 ng/dl, about 400 ng/dl, about 450 ng/dl, about 500 ng/dl, about 550 ng/dl, about 600 ng/dl, about 650 ng/dl, about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, and about 1100 ng/dl.