FORMULATIONS OF (R)-1-(2,2-DIFLUOROBENZO[D] [1,3] DIOXOL-5-YL)-N-(1-(2,3-DIHYDROXYPROPYL)-6-FLUORO-2-(1-HYDROXY-2-METHYLPROPAN-2-YL)-1H-INDOL-5-YL)CYCLOPROPANECARBOXAMIDE
The present invention relates to formulations of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1), pharmaceutical packs or kits thereof, and methods of treatment therewith.
1 - 37 . (canceled)
38 . A method of treating a CFTR mediated disease selected from male infertility and pancreatic insufficiency in a subject comprising administering to the subject an effective amount of a formulation comprising (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1), water, a surfactant which is vitamin E TPGS, and a polyethylene glycol (PEG) which is PEG 400.
39 - 42 . (canceled)
43 . The method of claim 38 , wherein the concentration of Compound 1 in the formulation is from about 0.05 to about 3% by weight.
44 . The method of claim 43 , wherein the concentration of Compound 1 in the formulation is from about 0.1 to about 2% by weight.
45 . The method of claim 43 , wherein the concentration of Compound 1 in the formulation is about 0.12, 0.25, or 0.50% by weight.
46 . The method of claim 43 , wherein the concentration of polyethylene glycol in the formulation is from about 40 to about 60% by weight.
47 . The method of claim 43 , wherein the concentration of polyethylene glycol in the formulation is from about 45 to about 55% by weight.
48 . The method of claim 43 , wherein the concentration of polyethylene glycol in the formulation is about 50% by weight.
49 . The method of claim 43 , wherein the concentration of Compound 1 in the formulation is from about 0.05 to about 3% by weight; and the concentration of polyethylene glycol is from about 40 to about 60% by weight.
50 . The method of claim 43 , wherein the concentration of Compound 1 in the formulation is from about 0.1 to about 2% by weight; and the concentration of polyethylene glycol is from about 45 to about 55% by weight.
51 . The method of claim 43 , wherein the concentration of Compound 1 in the formulation is about 0.12, 0.25, or 0.50% by weight; and the concentration of polyethylene glycol is about 50% by weight.
52 . The method of claim 43 , wherein the concentration of surfactant in the formulation is from about 5 to about 15% by weight.
53 . The method of claim 43 , wherein the concentration of surfactant in the formulation is from about 10 to about 12% by weight.
54 . The method of claim 43 , wherein the concentration of surfactant in the formulation is about 11% by weight.
55 . The method of claim 43 , wherein the concentration of Compound 1 in the formulation is from about 0.05 to about 3% by weight, the concentration of polyethylene glycol is from about 40 to about 60% by weight, and the concentration of surfactant is from about 5 to about 15% by weight.
56 . The method of claim 55 , wherein the concentration of Compound 1 in the formulation is from about 0.05 to about 3% by weight, the polyethylene glycol is PEG 400 at about 40 to about 60% by weight, and the surfactant is vitamin E TPGS at about 5 to 15% by weight.
57 . The method of claim 43 , wherein the formulation is about 30 to 50 g.
58 . The method of claim 43 , wherein the formulation is about 35 to 45 g.
59 . The method of claim 43 , wherein the formulation is about 40 g.
60 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (g)
Compound 1
0.05
PEG 400
19.95
Vitamin E TPGS
4.48
Water
15.52
61 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (g)
Compound 1
0.10
PEG 400
19.90
Vitamin E TPGS
4.48
Water
15.52
62 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (g)
Compound 1
0.20
PEG 400
19.80
Vitamin E TPGS
4.48
Water
15.52
63 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (g)
Compound 1
0.30
PEG 400
19.70
Vitamin E TPGS
4.48
Water
15.52
64 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (% by weight)
Compound 1
0.10-0.80
PEG 400
48-51
Vitamin E TPGS
10-12
Water
37-40
65 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (% by weight)
Compound 1
0.20-0.60
PEG 400
49-50
Vitamin E TPGS
10-12
Water
37-40
66 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (% by weight)
Compound 1
0.25
PEG 400
49.75
Vitamin E TPGS
11.20
Water
38.80
67 . The method of claim 43 , wherein the formulation comprises the following:
Component
Amount (% by weight)
Compound 1
0.50
PEG 400
49.50
Vitamin E TPGS
11.20
Water
38.80
68 . The method of claim 43 , wherein the formulation further comprises a taste masker.
69 . The method of claim 43 , wherein the formulation further comprises an additional therapeutic agent.
70 . The method of claim 43 , wherein the additional therapeutic agent is selected from a mucolytic agent, bronchodialator, an anti-biotic, an anti-infective agent, an anti-inflammatory agent, a CFTR modulator other than Compound 1, or a nutritional agent.