USE OF CICLESONIDE FOR THE TREATMENT OF RESPIRATORY DISEASES

Abstract

Disclosed herein are novel methods of treating respiratory diseases, and in particular the treatment of asthmatic children.

Claims

1. Method for treating or preventing a respiratory disease in a patient, which patient is a child and the method comprising administering to the patient a dose of a composition containing ciclesonide, a pharmaceutically acceptable salt, solvates or physiologically functional derivative thereof, wherein the dose of the composition comprises cyclesonide in an amount of from 20 to 200 μg.

2. Method according to claim 1, wherein the dose comprises 20, 40, 60, 80, 100, 120, 140, 160, 180 or 200 μg ciclesonide.

3. Method according to claim 1, wherein the dose comprises 40, 80 or 160 μg ciclesonide.

4. Method according to claim 1, wherein the child is a pre-pubertal human.

5. Method according to claim 1, wherein the child is a human from 6 to 12 years of age.

6. Method according to claim 1, wherein the dose is a daily dose in a continuous treatment regimen.

7. Method according to claim 6, wherein the treatment period is more than one day.

8. Method according to claim 7, wherein the treatment period is more than one week.

9. Method according to claim 1, which has no effect on growth rate of the patient.

10. Method according to claim 1, wherein the composition comprises a pharmaceutically acceptable carrier and/or one or more excipients.

11. Method according to claim 1 wherein ciclesonide is selected from the group of [11β,16α(R)]-16,17-[(Cyclohexylmethylen)bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxopropoxy)pregna-1,4-dien-3,20-dion, [11β,16α(S)]-16,17-[(Cyclohexylmethylen)bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxopro-p-oxy)pregna-1,4-dien3,20-dion, [11β,16α(R,S)]-16,17-[(Cyclohexyl-methylen)bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxoprop-oxy)pregna-1,4-dien3,20-dion, 16α,17-(22R)-Cyclohexylmethylendioxy-11β,21-dihydroxypregna-1,4-dien-3,20-dion, 16α,17-(22S)-Cyclohexylmethylenedioxy-11β,21-dihydroxypregna-1,4-dien-3,20-dion and 16α,17-(22R,S)-Cyclohexylmethylendioxy-11β,21-di-hydroxypregna-1,4-dien-3,20-dion.

12. Method according to claim 1, comprising a once daily dosage regimen.

13. Method according to claim, wherein the composition is suitable for administration by inhalation.

14. Method according to claim 13 wherein the composition is a pharmaceutical aerosol formulation comprising a therapeutically effective amount of ciclesonide and a hydrofluorocarbon propellant, preferably selected from 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and a mixture thereof, and cosolvent in an amount effective to solubilize ciclesonide and optionally a surfactant.

15. Method according to claim 14, wherein the cosolvent is ethanol.

16. Method according to claim 13 wherein the composition is a pharmaceutical aerosol formulation comprising particles of ciclesonide in a therapeutically effective amount and a hydrofluorocarbon propellant, preferably selected from 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and a mixture thereof, and 0.01 to 5% w/w based upon propellant of polar cosolvent and optionally a surfactant.

17. Method according to claim 13 wherein the composition is a dry powder and the carrier is a saccharide.

18. Method according to claim 13 wherein the carrier is lactose monohydrate.

19. Method according to claim 1, wherein the clinical condition is selected from the group of asthma, nocturnal asthma, exercise-induced asthma, chronic obstructive pulmonary diseases (COPD), chronic and wheezy bronchitis, emphysema, respiratory tract infection and upper respiratory tract disease, rhinitis, allergic and seasonal rhinitis.

20. Method according to claim 1, wherein the clinical condition is mild or moderate asthma.

21. Method according to claim 1, wherein the ciclesonide essentially consists of R epimer.

Description

EXAMPLES

Example 1

[0031] Ciclesonide is provided as pharmaceutical product comprising an aerosol vial equipped with a dispensing valve and containing the following formulation:

TABLE-US-00001 Ciclesonide 1.000 mg/ml Ethanol 94.800 mg/ml P134a 1090.200 mg/ml

Example 2

Clinical Study in Children with Asthma

[0032] The present study was conducted to determine the effects of ciclesonide at doses intended for the use in children on lower leg growth rate and HPA function in children with mild asthma.

[0033] METHODS: in a double blind, randomized, placebo-controlled, 4-period cross-over study, 24 children, 6 to 12 years of age, received ciclesonide 40, 80 and 160 μg or placebo via HFA-MDI once daily in the evening. Each 2-week treatment period was followed by a 2-week washout. Knemometry was performed at the beginning and the end of each treatment period. Cortisol levels in 12 h overnight urine were measured at the end of each treatment period.

[0034] RESULTS: No statistically significant differences were soon in lower-leg growth rates between any of the ciclesonide treatments and placebo; lower leg growth rates were 0.412 mm/week (placebo), 0.425 mm/week (ciclesonide 40 μg), 0.397 mm/week (80 μg), 0.370 mm/week (160 μg). There was no statistically significant dose-response effect. Likewise, no difference between the various treatments and no dose-dependency was found for urinary free cortisol adjusted for creatinine. All treatments were well tolerated.

[0035] CONCLUSIONS: Short-term lower leg growth rate and HPA-axis function of pre-pubertal children with mild asthma are not affected by treatment with ciclesonide in a dose range intended for the use in children.

[0036] Although the invention has been described in terms of preferred formulations and ingredients, it will be understood that these are not intended to be limiting. To the contrary, those skilled in the art will understand that various optional ingredients may be included, such as favouring agents, preservatives, additional active ingredients, and the like, while still embodying the present invention.