Treatment of diabetes mellitus by long-acting formulations of insulins

• US 10,092,513 B2
• Filed: 04/01/2014
• Issued: 10/09/2018
• Est. Priority Date: 04/03/2013
• Status: Active Grant

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Muhlen-Bartmer, Isabel, Ziemen, Monika
• Primary Examiner(s): Bradley, Christina
• Application Number:
  US14/781,857
• Publication Number:
  US 20160030339A1
• Time in Patent Office: 1,652 Days
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

The application relates to an aqueous pharmaceutical formulation for use in the treatment of Type I or Type II Diabetes Mellitus, wherein the treatment reduces the risk of nocturnal hypoglycemia, said formulation comprising 200-1000 U/mL [equimolar to 200-1000 IU human insulin] of insulin glargine, with the proviso that the concentration of said formulation is not 684 U/mL of insulin glargine.

Claims

1. A method of treating Type I or Type II Diabetes Mellitus in a patient comprising administering to the patient an aqueous pharmaceutical formulation, wherein the treatment reduces the risk of nocturnal hypoglycemia, wherein the aqueous pharmaceutical formulation comprises 200-1000 U/mL [equimolar to 200-1000 IU human insulin] of insulin glargine, with the proviso that the concentration of insulin glargine is not 684 U/mL, wherein the time interval between administrations is in the range of 20 hours to 23.5 hours or in the range of 24.5 hours to 28 hours on at least two days per week for the duration of treatment.

2. The method of claim 1, wherein the aqueous pharmaceutical formulation comprises 200 U/mL to 650 U/mL of insulin glargine [equimolar to 200-650 IU human insulin].

3. The method of claim 1, wherein the aqueous pharmaceutical formulation comprises 700 U/mL to 1000 U/mL of insulin glargine [equimolar to 700-1000 IU human insulin].

4. The method of claim 2, wherein the aqueous pharmaceutical formulation comprises 270-330 U/mL of insulin glargine [equimolar to 270-330 IU human insulin].

5. The method of claim 4, wherein the aqueous pharmaceutical formulation comprises 300 U/mL of insulin glargine [equimolar to 300 IU human insulin].

6. The method of claim 1, wherein the nocturnal hypoglycemia is selected from the group consisting of symptomatic hypoglycemia, severe symptomatic hypoglycemia, documented symptomatic hypoglycemia, probable symptomatic hypoglycemia, relative symptomatic hypoglycemia, and asymptomatic hypoglycemia.

7. The method of claim 1, wherein the patient to be treated has a HbA1c value of at least 8% at the onset of treatment.

8. The method of claim 1, wherein the patient to be treated is at least 60 years of age at the onset of treatment.

9. The method of claim 1, wherein the patient to be treated has a body mass index of at least 30 kg/m² at the onset of treatment.

10. The method of claim 1, wherein the patient to be treated received a basal insulin directly prior to the treatment.

11. The method of claim 1, wherein the patient to be treated received a mealtime short-acting insulin directly prior to the treatment.

12. The method of claim 10, wherein the patient to be treated has a pre-injection self-monitored plasma glucose of at least 9 mmol/L at the onset of treatment.

13. The method of claim 10, wherein the patient to be treated has a fasting plasma glucose concentration of at least 8 mmol/L at the onset of treatment.

14. The method of claim 1, wherein the formulation is administered once daily in the evening at a predetermined time.

15. The method of claim 1, wherein the patient additionally receives a mealtime short-acting insulin.

16. The method of claim 1, wherein the aqueous pharmaceutical formulation comprises one or more excipients selected from the group consisting of zinc, m-cresol, glycerol, polysorbate 20, and sodium.

17. The method of claim 16, wherein the aqueous pharmaceutical formulation comprises 90 μ

g/mL zinc, 2.7 mg/mL m-cresol, and 20 mg/ml glycerol 85%.

18. The method of claim 16, wherein the aqueous pharmaceutical formulation comprises 90 μ

g/mL zinc, 2.7 mg/mL m-cresol, 20 μ

g/mL polysorbate 20, and 20 mg/mL glycerol 85%.

19. The method of claim 1, wherein the pH of the aqueous pharmaceutical formulation is between 3.4 and 4.6.

20. The method of claim 19, wherein the pH of the aqueous pharmaceutical formulation is 4.

21. The method of claim 19, wherein the pH of the aqueous pharmaceutical formulation is 4.5.

22. The method of claim 1, wherein the Type I or Type II Diabetes Mellitus is Type II Diabetes Mellitus.

23. The method of claim 22, wherein the Type II Diabetes Mellitus is not adequately controlled with at least one oral antihyperglycemic alone.

24. The method of claim 23, wherein the at least one oral antihyperglycemic is metformin.

25. The method of claim 24, wherein a treatment with at least 1.5 g/day of metformin does not adequately control the Type II Diabetes Mellitus.

26. The method of claim 22, wherein the aqueous pharmaceutical formulation is administered in combination with at least one oral antihyperglycemic agent.

27. The method of claim 26, wherein the at least one antihyperglycemic agent is metformin.

28. The method of claim 1, wherein the aqueous pharmaceutical formulation is administered on at least three days per week.

29. The method of claim 1, wherein the aqueous pharmaceutical formulation is administered on at least four days per week.

30. The method of claim 1, wherein the time interval between administrations is in the range of 20 hours to 23 hours or in the range of 25 hours to 28 hours.

31. The method of claim 1, wherein the time interval between administrations is in the range of 21 hours to 23 hours or in the range of 25 hours to 27 hours.

32. The method of claim 1, wherein the time interval between administrations is in the range of 21.5 hours to 23 hours or in the range of 25 hours to 26.5 hours.

33. A method of treating Type I or Type II Diabetes Mellitus in a patient comprising administering to the patient an aqueous pharmaceutical formulation comprising 300 U/mL insulin glargine [equimolar to 300 IU human insulin], wherein the time interval between administrations is in the range of 20 hours to 23.5 hours or in the range of 24.5 hours to 28 hours on at least two days per week for the duration of treatment.

34. The method of claim 33, wherein the pharmaceutical composition further comprises excipients selected from the group consisting of zinc, m-cresol, glycerol, polysorbate 20, and sodium.

35. The method of claim 33, wherein the pharmaceutical composition further comprises excipients selected from the group consisting of zinc, m-cresol, glycerol, and sodium.