9-aminomethyl minocycline compounds and uses thereof
View Patent ↗Methods and compositions for using a tetracycline compound to treat bacterial infections are described. In one embodiment, for example, the invention provides a method of treating a subject for an infection, comprising administering to said subject an effective amount of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof, such that said subject is treated, wherein the 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline is administered orally at a dose of about 450 mg per day for two consecutive days, then at a dose of about 300 mg per day for 5 or more days.
1. A method of treating a human subject in need of treatment for a bacterial skin or skin structure infection, comprising orally administering to said subject an effective amount of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof, such that said subject is treated, wherein said 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline is administered orally at a dose of about 450 mg per day for two consecutive days, then at a dose of about 300 mg per day for 5 or more days.
2. The method of claim 1 , wherein the bacterial skin or skin structure infection is wound infection, cellulitis/erysipelas, major abscess, furuncles/boils, carbuncle, Staphylococcal scalded skin syndrome (SSSS), or ecthyma.
3. The method of claim 1 , wherein the bacterial skin or skin structure infection is Acute Bacterial Skin and Skin Structure Infection (ABSSSI).
4. The method of claim 3 , wherein the ABSSSI is community-acquired ABSSSI.
5. The method of claim 4 , wherein the ABSSSI comprises wound infection, cellulitis/erysipelas, and/or major abscess.
6. The method of claim 1 , wherein said bacterial skin or skin structure infection is a result of skin injury including but not limited to trauma, a surgical procedure, or IV drug use.
7. The method of claim 1 , wherein said human subject is administered 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline under fasting condition.
8. The method of claim 1 , wherein said 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline is administered once per day.
9. The method of claim 1 , wherein said subject is treated up to and including about 14 days, up to and including about 10 days, up to and including about 9 days, up to and including about 8 days, or up to and including about 7 days, up to and including about 5 days, such that said subject is treated.
10. The method of claim 9 , wherein said subject is treated for 7-10 days.
11. The method of claim 1 , wherein said salt is a tosylate salt.
12. The method of claim 1 , wherein said bacterial skin or skin structure infection is known or suspected to be caused by Gram-positive pathogens selected from the group consisting of: Staphylococcus aureus, Staphylococcus lugdunensis, Streptococcus species, Streptococcus agalactiae, Streptococcus mitis, Enterococcus species ( Enterococcus faecalis (such as VRE or VSE), or Enterococcus faecium (such as VRE or VSE)), Streptococcus anginosus group ( S. anginosus, S. constellatus , and S. intermedius , that is beta-, alpha- or non-hemolytic), Viridans group Streptococci (VGS), Clostridium perfringens, Finegoldia magna , and a combination thereof.
13. The method of claim 12 , wherein:
(a) said Staphylococcus aureus is methicillin-resistant Staphylococcus aureus (MRSA), or methicillin-susceptible Staphylococcus aureus (MSSA);
(b) said Streptococcus species include Streptococcus anginosus group;
(c) said Streptococcus species include beta-hemolytic Streptococci or S. anginosus;
(d) said Streptococcus species include non-hemolytic Streptococci or S. intermedius;
(e) said Streptococcus species include alpha-hemolytic Streptococci or S. constellatus;
(f) said Enterococcus species include Enterococcus faecalis (VSE); or,
(g) said Streptococcus species include Streptococcus pyogenes.
14. The method of claim 1 , wherein said bacterial skin or skin structure infection is known or suspected to be caused by Gram-negative pathogens selected from the group consisting of: Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Prevotella denticola, Prevotella melaninogenica , and a combination thereof.
15. The method of claim 1 , wherein GI adverse events (AEs) associated with treatment are predominantly mild, or do not result in discontinuation of therapy.
16. The method of claim 1 , wherein Area Under the Curve from 0-24 hours (AUC 0-24 ) after the first two doses of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof is about 10,000 ng*h/mL.
17. The method of claim 1 , wherein each dose of said 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or salt thereof is administered as 150 mg tablets.