0216-ERI-01 150 Product Information Capsule 150mg Vismodegib 026444 - (vismodegib)- ( ) [ (5.1)(8.1, 8.6)] 1 (Locally Advanced) 2 150 mg[ (14)] / 3 (vismodegib) 150 mg 150 mg VISMO 4
0216-ERI-01 Product Information 4.1 24 4.2 ( St John s wort) 5 5.1-150 mg/day vismodegib ( ) ( ) - ( ) 24 () () [ (8.1, 8.6)] 5.2 24 5.3 2 6 6.1 4 138 (BCC) 150 mg 61 ( 21-101 ) 100% () 64% 10 (305 0.7-36 ) 111 6
0216-ERI-01 Product Information 4 1 2 138 150 mg >150mg >150mg ( 10%) ( 1) 10% ADRs
1(BCC) 10% (138 ) MedDRA 1 2 (%) 3 (%) 4 (%) 48 (34.8%) 0 0 46(33.3%) 3 (2.2%) 0 32(23.2%) 0 0 23 16.7%) 0 0 15 (10.9%) 0 0 65 (47.1%) 8 (5.8%) 1 (0.7%) 69 (50.0%) 14 (10.1%) 0 41 (29.7%) 3 (2.2%) 0 103 (74.6%) 7 (5.1%) 0 23 (16.7%) 1 (0.7%) 0 14 (10.1%) 1 (0.7%) 0 81 (58.7%) 0 0 15 (10.9%) 0 0 91 (65.9%) 0 0 1 MedDRA = 2 (NCI)(CTCAE) >10% : (Reproductive Disorders) 138 10 3 (30%)[(12.1] <10% ** (flank pain) (hypogeusia) 4 Product Information
** (AST) (GGT) 3 6 (4%) 2 (1%) 3 (2%) 7 7.1 vismodegib Vismodegib CYP450 vismodegib CYP450 vismodegib fluconazole ( CYP2C9 ) itraconazole ( CYP3A4 ) vismodegib CYP (rifampicin, carbamazepine, phenytoin, St. John s wort) vismodegib vismodegib P- vismodegib itraconazole ( P-) ph vismodegib ph vismodegib 2 20 mg rabeprazole ( ) vismodegib 33% vismodegib rabeprazole Comment [CJ1]: TFDA (103.10.28) EMA 7.2 Vismodegib vismodegib CYP450 vismodegib rosiglitazone (CYP2C8 ) vismodegib CYP vismodegib ethinyl estradiol norethindrone 7 vismodegib 5 Product Information
vismodegib BCRP(breast cancer resistance protein) vismodegib (BCRP) vismodegib vismodegib OATP1B1 vismodegib OATP1B1 bosentan glibenclamide repaglinide valsartan statins vismodegib statin 8 8.1 D vismodegib 20% ( AUC 0-24 hr )vismodegib ( ) ( ) vismodegib vismodegib [ (5.1)] - vismodegib 10 60 300 mg/kg/day 60 mg/kg/day( (AUC) 2 ) 100% 10 mg/kg/day( AUC 0.2 ) (( ) / ( ))( ) 8.3 vismodegib 8.4 vismodegib 26 vismodegib 50 mg/kg/day ( (AUC) 0.4 ) vismodegib 15 mg/kg/day ( AUC AUC 0.2 ) ( / ) 8.5 6 Product Information
65 8.6 () [ (5.1)(8.1)] 7 ( <1%) 24 [ (6) (12.1)] Vismodegib - 2 ( ) 2 8.7 Vismodegib vismodegib vismodegib [ (11.2)] 8.8 vismodegib vismodegib [ (11.2)] Comment [CJ2]: TFDA (103.10.28) 24M 9 540 mg 150 mg 540 mg 10 Vismodegib Hedgehog (Hh) 2-Chloro-N-(4-chloro-3-(pyridin-2- yl)phenyl) -4-(methylsulfonyl)benzamide C 19 H 14 Cl 2 N 2 O 3 S 421.30 g/mol 7 Product Information
Vismodegib pka (pyridinium ) 3.8 Vismodegib ph ph=7 0.1 μg/ml ph=1 0.99 mg/ml (log P) 2.7 (vismodegib) 150 mg vismodegib ( ) 11 11.1 Vismodegib Hedgehog Vismodegib Smoothened ( Hedgehog ) 11.2 Vismodegib ( 2 (BCS Class 2)) Vismodegib 31.8% Vismodegib 270 mg 540 mg vismodegib Vismodegib 16.4~26.6 L Vismodegib 99% Vismodegib α1- (AAG) AAG 98%Vismodegib CYP2C9 CYP3A4/5 Vismodegib 82% 4.4% Vismodegib (t 1/2 ) 4 12 8 Product Information
vismodegib (<5%) vismodegib ( 50 80 / n = 58) ( 30 50 / n = 16) ( <30 / n = 1) vismodegib Vismodegib / ( AST [TB] ) ( NCI- ODWG n = 8) ( NCI-ODWG n = 6) ( NCI-ODWG n = 3) vismodegib (n = 9) (comparable) NCI-ODWG (TB[ULN] AST>ULN ULN<TB 1.5xULN AST) (1.5xULN<TB<3xULN AST) (3xULN<TB<10xULN AST) 11.3 60 QTc QTc 12 12.1 Vismodegib vismodegib 100 mg/kg/day( (AUC) 0.8 )26 (pilomatricoma) Vismodegib (Ames) Vismodegib 26 15 mg/kg/day( AUC AUC 0.3 ) vismodegib 50 mg/kg/day ( AUC AUC 2 ) 4 13 26 vismodegib 100 mg/kg/day ( AUC AUC 0.8 ) 26 12.2 vismodegib 50 mg/kg/day ( AUC AUC 0.4 ) 4 9 Product Information
13 2 104 (mbcc 33 )(labcc 71 ) ( Gorlin ) 150 mg (ORR)(IRF) (mbcc)(recist) 1.0 (labcc) ()( ) (labcc) (1)( (SLD)) 30% (2) (SLD) 30% (3) ( ) (1) (SLD) 20% ( ) (2) 2 (3) (4) (RECIST) 104 96 Gorlin 21% 62 ( 65 46%) 61% 100% (mbcc)(33 ) 97% (97%)(58%)(30%) (labcc) (63 ) 94% (89%) (27%)/(11%) 10.2 ( 0.7-18.7 ) 2 10 Product Information
2 1 mbcc (n = 33) labcc (n = 63) 2 (%) (95% ) 10 (30.3) (15.6, 48.2) 27 (42.9) (30.5, 56.0) 3 0 (0.0) 13 (20.6) 10 (30.3) 14 (22.2) ( ) (95% 5 ) 7.6 7.6 (5.6, NE 4 ) (5.7, 9.7) 1 2 IRF 3 (labcc) 4 NE 5 CI = 14 30 o C 2-1000 CDS 4.0_USPI 01/30/2012 2014 10 0515-ERI-3B01 Patheon Inc. 2100 Syntex Court, Mississauga, Ontario L5N 7K9, Canada. F. Hoffmann-La Roche Ltd. Wurmisweg, CH-4303 Kaiseraugst, Switzerland. 羅 : 北 3 134 9 樓 :(02)27153111 羅 羅 11 Product Information