gilead sciences, inc. safety analysis set...gilead sciences, inc. filgotinib ra j-iss week 24 table...

Gilead Sciences, Inc.

Filgotinib RA J-ISS Week 24

Table 1: Subject Disposition (GS-US-417-0301, GS-US-417-0302 and GS-US-417-0303)

Safety Analysis Set

As Randomized Subjects

_______________________________________________________________________________________________________________________________________

Japan Subjects

_________________________________________________________________________________

Filgotinib Filgotinib

200 mg 100 mg Adalimumab Other Total

_______________________________________________________________________________________________________________________________________

Safety Analysis Set 87 67 28 76 258

Study Drug Completion Status Up to Week 24

Completed Study Drug 79 ( 90.8%) 58 ( 86.6%) 22 ( 78.6%) 54 ( 71.1%) 213 ( 82.6%)

Prematurely Discontinued Study Drug 8 ( 9.2%) 9 ( 13.4%) 6 ( 21.4%) 22 ( 28.9%) 45 ( 17.4%)

Study Drug Completion Status

On Study Drug 53 ( 60.9%) 35 ( 52.2%) 15 ( 53.6%) 35 ( 46.1%) 138 ( 53.5%)



Reason for Premature Discontinuation of Study Drug

Lack of Efficacy 5 ( 5.7%) 7 ( 10.4%) 4 ( 14.3%) 16 ( 21.1%) 32 ( 12.4%)

Subject Decision 0 2 ( 3.0%) 0 1 ( 1.3%) 3 ( 1.2%)

Adverse Event 6 ( 6.9%) 0 3 ( 10.7%) 7 ( 9.2%) 16 ( 6.2%)

Lost to Follow-Up 0 0 0 0 0

Investigator's Discretion 0 0 0 3 ( 3.9%) 3 ( 1.2%)

Protocol Violation 0 0 0 1 ( 1.3%) 1 ( 0.4%)

Death 0 0 0 0 0

Non-Compliance With Study Drug 0 0 0 0 0

Pregnancy 0 0 0 0 0

______________________________________________________________________________________________________________________________________________________

Safety Analysis Set includes subjects who received at least 1 dose of study drug of filgotinib 100 mg QD, filgotinib 200 mg QD, adalimumab,

or other (Placebo with or without MTX or csDMARDs, and MTX monotherapy).

Percentages for completion status were calculated based on the number of subjects in the Safety Analysis Set.

For GS-US-417-0301 subjects who were on placebo, they will be considered as completed Week 24 study drug if they were re-randomized.

For GS-US-417-0301 subjects who were on placebo but were not re-randomized, and for subjects who remained on the same treatment in

GS-US-417-0301 and GS-US-417-0303 they will be considered as completed Week 24 study drug if study drug was taken for at least 156 days.

Data Extracted: GS-US-417-0301:05Feb2019; GS-US-417-0302:24Aug2018; GS-US-417-0303:17Jan2019; GS-US-417-0304:11Feb2019; GLPG0634-CL-205:08Aug2018.

Source: .../wk24_japan/version1/prog/t-disp.sas v9.4 Output file: t-disp-rand.out 24MAY2019:22:51 Page 1 of 6

1




Safety Analysis Set


_______________________________________________________________________________________________________________________________________

Non-Japan Subjects

_________________________________________________________________________________


(Continued) 200 mg 100 mg Adalimumab Other Total

_______________________________________________________________________________________________________________________________________






On Study Drug 557 ( 48.0%) 324 ( 41.9%) 144 ( 48.5%) 411 ( 42.7%) 1436 ( 45.0%)




Lack of Efficacy 55 ( 4.7%) 41 ( 5.3%) 8 ( 2.7%) 91 ( 9.4%) 195 ( 6.1%)

Subject Decision 40 ( 3.4%) 39 ( 5.0%) 14 ( 4.7%) 64 ( 6.6%) 157 ( 4.9%)

Adverse Event 45 ( 3.9%) 25 ( 3.2%) 15 ( 5.1%) 34 ( 3.5%) 119 ( 3.7%)

Lost to Follow-Up 23 ( 2.0%) 9 ( 1.2%) 1 ( 0.3%) 18 ( 1.9%) 51 ( 1.6%)

Investigator's Discretion 12 ( 1.0%) 10 ( 1.3%) 4 ( 1.3%) 15 ( 1.6%) 41 ( 1.3%)

Protocol Violation 0 2 ( 0.3%) 3 ( 1.0%) 3 ( 0.3%) 8 ( 0.3%)

Death 5 ( 0.4%) 1 ( 0.1%) 0 2 ( 0.2%) 8 ( 0.3%)

Non-Compliance With Study Drug 3 ( 0.3%) 2 ( 0.3%) 0 3 ( 0.3%) 8 ( 0.3%)

Pregnancy 1 (




Safety Analysis Set


_______________________________________________________________________________________________________________________________________

Overall

_________________________________________________________________________________



_______________________________________________________________________________________________________________________________________






On Study Drug 610 ( 48.9%) 359 ( 42.7%) 159 ( 48.9%) 446 ( 42.9%) 1574 ( 45.6%)




Lack of Efficacy 60 ( 4.8%) 48 ( 5.7%) 12 ( 3.7%) 107 ( 10.3%) 227 ( 6.6%)

Subject Decision 40 ( 3.2%) 41 ( 4.9%) 14 ( 4.3%) 65 ( 6.3%) 160 ( 4.6%)

Adverse Event 51 ( 4.1%) 25 ( 3.0%) 18 ( 5.5%) 41 ( 3.9%) 135 ( 3.9%)

Lost to Follow-Up 23 ( 1.8%) 9 ( 1.1%) 1 ( 0.3%) 18 ( 1.7%) 51 ( 1.5%)



Death 5 ( 0.4%) 1 ( 0.1%) 0 2 ( 0.2%) 8 ( 0.2%)


Pregnancy 1 (




Safety Analysis Set


_______________________________________________________________________________________________________________________________________

Japan Subjects

_________________________________________________________________________________


200 mg 100 mg Adalimumab Other Total

_______________________________________________________________________________________________________________________________________

Study Completion Status

On Study 60 ( 69.0%) 39 ( 58.2%) 20 ( 71.4%) 46 ( 60.5%) 165 ( 64.0%)

Completed Study 25 ( 28.7%) 26 ( 38.8%) 6 ( 21.4%) 22 ( 28.9%) 79 ( 30.6%)

Prematurely Discontinued Study 2 ( 2.3%) 2 ( 3.0%) 2 ( 7.1%) 8 ( 10.5%) 14 ( 5.4%)

Reason for Premature Discontinuation of Study

Withdrew Consent 0 1 ( 1.5%) 1 ( 3.6%) 1 ( 1.3%) 3 ( 1.2%)

Investigator's Discretion 0 1 ( 1.5%) 0 4 ( 5.3%) 5 ( 1.9%)

Adverse Event 2 ( 2.3%) 0 1 ( 3.6%) 2 ( 2.6%) 5 ( 1.9%)

Lost to Follow-Up 0 0 0 0 0

Protocol Violation 0 0 0 1 ( 1.3%) 1 ( 0.4%)

Death 0 0 0 0 0

Non-Compliance With Study Drug 0 0 0 0 0

Pregnancy 0 0 0 0 0

Study Terminated By Sponsor 0 0 0 0 0

______________________________________________________________________________________________________________________________________________________



Percentages for completion status were calculated based on the number of subjects in the Safety Analysis Set.

For GS-US-417-0301 subjects who were on placebo, they will be considered as completed Week 24 study drug if they were re-randomized.

For GS-US-417-0301 subjects who were on placebo but were not re-randomized, and for subjects who remained on the same treatment in

GS-US-417-0301 and GS-US-417-0303 they will be considered as completed Week 24 study drug if study drug was taken for at least 156 days.


Source: .../wk24_japan/version1/prog/t-disp.sas v9.4 Output file: t-disp-rand.out 24MAY2019:22:51 Page 4 of 6

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Safety Analysis Set


_______________________________________________________________________________________________________________________________________

Non-Japan Subjects

_________________________________________________________________________________



_______________________________________________________________________________________________________________________________________


On Study 590 ( 50.8%) 349 ( 45.1%) 154 ( 51.9%) 451 ( 46.8%) 1544 ( 48.3%)

Completed Study 434 ( 37.4%) 332 ( 42.9%) 109 ( 36.7%) 348 ( 36.1%) 1223 ( 38.3%)



Withdrew Consent 56 ( 4.8%) 47 ( 6.1%) 17 ( 5.7%) 92 ( 9.6%) 212 ( 6.6%)


Adverse Event 24 ( 2.1%) 14 ( 1.8%) 5 ( 1.7%) 17 ( 1.8%) 60 ( 1.9%)

Lost to Follow-Up 23 ( 2.0%) 10 ( 1.3%) 2 ( 0.7%) 20 ( 2.1%) 55 ( 1.7%)


Death 5 ( 0.4%) 2 ( 0.3%) 1 ( 0.3%) 2 ( 0.2%) 10 ( 0.3%)


Pregnancy 1 (




Safety Analysis Set


_______________________________________________________________________________________________________________________________________

Overall

_________________________________________________________________________________



_______________________________________________________________________________________________________________________________________


On Study 650 ( 52.1%) 388 ( 46.2%) 174 ( 53.5%) 497 ( 47.8%) 1709 ( 49.5%)

Completed Study 459 ( 36.8%) 358 ( 42.6%) 115 ( 35.4%) 370 ( 35.6%) 1302 ( 37.7%)



Withdrew Consent 56 ( 4.5%) 48 ( 5.7%) 18 ( 5.5%) 93 ( 9.0%) 215 ( 6.2%)


Adverse Event 26 ( 2.1%) 14 ( 1.7%) 6 ( 1.8%) 19 ( 1.8%) 65 ( 1.9%)

Lost to Follow-Up 23 ( 1.8%) 10 ( 1.2%) 2 ( 0.6%) 20 ( 1.9%) 55 ( 1.6%)


Death 5 ( 0.4%) 2 ( 0.2%) 1 ( 0.3%) 2 ( 0.2%) 10 ( 0.3%)


Pregnancy 1 (



Table 2.1: Demographics and Baseline Characteristics (GS-US-417-0301, GS-US-417-0302, GS-US-417-0303, GLPG0634-CL-203 and GLPG0634-CL-204)

Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Japan Subjects

_____________________________________________________________________________________________

Filgotinib Filgotinib Filgotinib

200 mg 100 mg Total Adalimumab Other Total

(N=87) (N=67) (N=154) (N=28) (N=76) (N=258)

____________________________________________________________________________________________________________________________________________________

Age (years)

N 87 67 154 28 76 258

Mean (SD) 54 (13.0) 56 (11.0) 55 (12.2) 54 (10.5) 56 (11.5) 55 (11.8)

Median 56 56 56 56 57 56

Q1, Q3 47, 64 47, 65 47, 64 46, 64 48, 64 48, 64

Min, Max 21, 80 28, 78 21, 80 34, 68 21, 77 21, 80

Age Group

< 65 years 66 ( 75.9%) 50 ( 74.6%) 116 ( 75.3%) 24 ( 85.7%) 58 ( 76.3%) 198 ( 76.7%)

>= 65 years 21 ( 24.1%) 17 ( 25.4%) 38 ( 24.7%) 4 ( 14.3%) 18 ( 23.7%) 60 ( 23.3%)

Sex at Birth

Male 23 ( 26.4%) 17 ( 25.4%) 40 ( 26.0%) 6 ( 21.4%) 22 ( 28.9%) 68 ( 26.4%)

Female 64 ( 73.6%) 50 ( 74.6%) 114 ( 74.0%) 22 ( 78.6%) 54 ( 71.1%) 190 ( 73.6%)

______________________________________________________________________________________________________________________________________________________


or other (Placebo with or without MTX or csDMARDs, and MTX monotherapy). Not Permitted = local regulators did not allow collection of information.

Denominator for percentages was the Safety Analysis Set. Age was calculated from date of first study drug administration in the parent study.

Geographic Region: Group A: Australia, Austria, Belgium, Canada, France, Germany, Ireland, Israel, Italy, Netherlands, New Zealand, Republic of Korea,

Singapore, South Africa, Spain, Sweden, Switzerland, United Kingdom, and USA; Group B: Bulgaria, Croatia, Czech Republic, Estonia, India, Latvia,

Georgia, Hungary, Moldova, Poland, Romania, Russia, Slovakia, Serbia and Ukraine; Group C: Argentina, Brazil, Chile, Colombia, Guatemala,

Mexico, Peru and Puerto Rico; Group D: China, Hong Kong, Malaysia, Philippines, Taiwan, Thailand and Vietnam; Group E: Japan


Source: .../wk24_japan/version1/prog/t-demog.sas v9.4 Output file: t-demog-rand.out 24MAY2019:22:51 Page 1 of 9

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Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Non-Japan Subjects

_____________________________________________________________________________________________



(Continued) (N=1316) (N=928) (N=2244) (N=297) (N=1121) (N=3662)

____________________________________________________________________________________________________________________________________________________

Age (years)

N 1316 928 2244 297 1121 3662

Mean (SD) 53 (13.2) 53 (12.5) 53 (12.9) 53 (13.1) 53 (13.1) 53 (13.0)

Median 53 54 54 55 54 54

Q1, Q3 44, 62 45, 62 44, 62 44, 63 44, 62 44, 62

Min, Max 18, 85 19, 86 18, 86 18, 81 18, 87 18, 87

Age Group

< 65 years 1075 ( 81.7%) 755 ( 81.4%) 1830 ( 81.6%) 234 ( 78.8%) 894 ( 79.8%) 2958 ( 80.8%)

>= 65 years 241 ( 18.3%) 173 ( 18.6%) 414 ( 18.4%) 63 ( 21.2%) 227 ( 20.2%) 704 ( 19.2%)

Sex at Birth

Male 256 ( 19.5%) 184 ( 19.8%) 440 ( 19.6%) 53 ( 17.8%) 225 ( 20.1%) 718 ( 19.6%)

Female 1060 ( 80.5%) 744 ( 80.2%) 1804 ( 80.4%) 244 ( 82.2%) 896 ( 79.9%) 2944 ( 80.4%)

______________________________________________________________________________________________________________________________________________________










8




Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Overall

_____________________________________________________________________________________________




____________________________________________________________________________________________________________________________________________________

Age (years)

N 1403 995 2398 325 1197 3920

Mean (SD) 53 (13.2) 53 (12.4) 53 (12.9) 53 (12.9) 53 (13.0) 53 (12.9)

Median 54 54 54 55 55 54

Q1, Q3 44, 62 45, 62 45, 62 44, 63 45, 63 44, 62

Min, Max 18, 85 19, 86 18, 86 18, 81 18, 87 18, 87

Age Group

< 65 years 1141 ( 81.3%) 805 ( 80.9%) 1946 ( 81.2%) 258 ( 79.4%) 952 ( 79.5%) 3156 ( 80.5%)

>= 65 years 262 ( 18.7%) 190 ( 19.1%) 452 ( 18.8%) 67 ( 20.6%) 245 ( 20.5%) 764 ( 19.5%)

Sex at Birth

Male 279 ( 19.9%) 201 ( 20.2%) 480 ( 20.0%) 59 ( 18.2%) 247 ( 20.6%) 786 ( 20.1%)

Female 1124 ( 80.1%) 794 ( 79.8%) 1918 ( 80.0%) 266 ( 81.8%) 950 ( 79.4%) 3134 ( 79.9%)

______________________________________________________________________________________________________________________________________________________










9




Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Japan Subjects

_____________________________________________________________________________________________



(N=87) (N=67) (N=154) (N=28) (N=76) (N=258)

____________________________________________________________________________________________________________________________________________________

Race

American Indian or Alaska Native 0 0 0 0 0 0

Asian 87 (100.0%) 67 (100.0%) 154 (100.0%) 28 (100.0%) 76 (100.0%) 258 (100.0%)

Black or African American 0 0 0 0 0 0

Native Hawaiian or Pacific Islander 0 0 0 0 0 0

White 0 0 0 0 0 0

Other 0 0 0 0 0 0

Not Permitted 0 0 0 0 0 0

Ethnicity

Hispanic or Latino 0 1 ( 1.5%) 1 ( 0.6%) 0 0 1 ( 0.4%)

Not Hispanic or Latino 87 (100.0%) 66 ( 98.5%) 153 ( 99.4%) 28 (100.0%) 76 (100.0%) 257 ( 99.6%)

Not Permitted 0 0 0 0 0 0

______________________________________________________________________________________________________________________________________________________










10




Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Non-Japan Subjects

_____________________________________________________________________________________________




____________________________________________________________________________________________________________________________________________________

Race

American Indian or Alaska Native 77 ( 5.9%) 47 ( 5.1%) 124 ( 5.5%) 19 ( 6.4%) 70 ( 6.2%) 213 ( 5.8%)

Asian 187 ( 14.2%) 120 ( 12.9%) 307 ( 13.7%) 37 ( 12.5%) 132 ( 11.8%) 476 ( 13.0%)

Black or African American 44 ( 3.3%) 28 ( 3.0%) 72 ( 3.2%) 10 ( 3.4%) 49 ( 4.4%) 131 ( 3.6%)

Native Hawaiian or Pacific Islander 3 ( 0.2%) 0 3 ( 0.1%) 0 6 ( 0.5%) 9 ( 0.2%)

White 955 ( 72.6%) 680 ( 73.3%) 1635 ( 72.9%) 227 ( 76.4%) 806 ( 71.9%) 2668 ( 72.9%)

Other 49 ( 3.7%) 52 ( 5.6%) 101 ( 4.5%) 4 ( 1.3%) 54 ( 4.8%) 159 ( 4.3%)

Not Permitted 1 (




Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Overall

_____________________________________________________________________________________________




____________________________________________________________________________________________________________________________________________________

Race

American Indian or Alaska Native 77 ( 5.5%) 47 ( 4.7%) 124 ( 5.2%) 19 ( 5.8%) 70 ( 5.8%) 213 ( 5.4%)

Asian 274 ( 19.5%) 187 ( 18.8%) 461 ( 19.2%) 65 ( 20.0%) 208 ( 17.4%) 734 ( 18.7%)

Black or African American 44 ( 3.1%) 28 ( 2.8%) 72 ( 3.0%) 10 ( 3.1%) 49 ( 4.1%) 131 ( 3.3%)

Native Hawaiian or Pacific Islander 3 ( 0.2%) 0 3 ( 0.1%) 0 6 ( 0.5%) 9 ( 0.2%)

White 955 ( 68.1%) 680 ( 68.3%) 1635 ( 68.2%) 227 ( 69.8%) 806 ( 67.3%) 2668 ( 68.1%)

Other 49 ( 3.5%) 52 ( 5.2%) 101 ( 4.2%) 4 ( 1.2%) 54 ( 4.5%) 159 ( 4.1%)

Not Permitted 1 (




Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Japan Subjects

_____________________________________________________________________________________________



(N=87) (N=67) (N=154) (N=28) (N=76) (N=258)

____________________________________________________________________________________________________________________________________________________

Geographic Region

Group A 0 0 0 0 0 0

Group B 0 0 0 0 0 0

Group C 0 0 0 0 0 0

Group D 0 0 0 0 0 0

Group E 87 (100.0%) 67 (100.0%) 154 (100.0%) 28 (100.0%) 76 (100.0%) 258 (100.0%)

Concurrent Oral Corticosteroids Use on First Dosing

Date in Parent Study

Yes 29 ( 33.3%) 21 ( 31.3%) 50 ( 32.5%) 8 ( 28.6%) 31 ( 40.8%) 89 ( 34.5%)

No 58 ( 66.7%) 46 ( 68.7%) 104 ( 67.5%) 20 ( 71.4%) 45 ( 59.2%) 169 ( 65.5%)

Concurrent csDMARDs Use on First Dosing Date in

Parent Study

Yes 75 ( 86.2%) 67 (100.0%) 142 ( 92.2%) 28 (100.0%) 76 (100.0%) 246 ( 95.3%)

No 12 ( 13.8%) 0 12 ( 7.8%) 0 0 12 ( 4.7%)

Prior Exposure to bDMARDs on First dosing Date in

Parent Study

Yes 12 ( 13.8%) 15 ( 22.4%) 27 ( 17.5%) 0 13 ( 17.1%) 40 ( 15.5%)

No 75 ( 86.2%) 52 ( 77.6%) 127 ( 82.5%) 28 (100.0%) 63 ( 82.9%) 218 ( 84.5%)

______________________________________________________________________________________________________________________________________________________










13




Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Non-Japan Subjects

_____________________________________________________________________________________________




____________________________________________________________________________________________________________________________________________________

Geographic Region

Group A 502 ( 38.1%) 326 ( 35.1%) 828 ( 36.9%) 73 ( 24.6%) 412 ( 36.8%) 1313 ( 35.9%)

Group B 573 ( 43.5%) 428 ( 46.1%) 1001 ( 44.6%) 175 ( 58.9%) 499 ( 44.5%) 1675 ( 45.7%)

Group C 200 ( 15.2%) 148 ( 15.9%) 348 ( 15.5%) 35 ( 11.8%) 172 ( 15.3%) 555 ( 15.2%)

Group D 41 ( 3.1%) 26 ( 2.8%) 67 ( 3.0%) 14 ( 4.7%) 38 ( 3.4%) 119 ( 3.2%)

Group E 0 0 0 0 0 0



Yes 463 ( 35.2%) 336 ( 36.2%) 799 ( 35.6%) 121 ( 40.7%) 408 ( 36.4%) 1328 ( 36.3%)

No 853 ( 64.8%) 592 ( 63.8%) 1445 ( 64.4%) 176 ( 59.3%) 713 ( 63.6%) 2334 ( 63.7%)


Parent Study

Yes 1069 ( 81.2%) 861 ( 92.8%) 1930 ( 86.0%) 297 (100.0%) 1052 ( 93.8%) 3279 ( 89.5%)

No 247 ( 18.8%) 67 ( 7.2%) 314 ( 14.0%) 0 69 ( 6.2%) 383 ( 10.5%)


Parent Study

Yes 169 ( 12.8%) 165 ( 17.8%) 334 ( 14.9%) 8 ( 2.7%) 151 ( 13.5%) 493 ( 13.5%)

No 1147 ( 87.2%) 763 ( 82.2%) 1910 ( 85.1%) 289 ( 97.3%) 970 ( 86.5%) 3169 ( 86.5%)

______________________________________________________________________________________________________________________________________________________










14




Safety Analysis Set


____________________________________________________________________________________________________________________________________________________

Overall

_____________________________________________________________________________________________




____________________________________________________________________________________________________________________________________________________

Geographic Region

Group A 502 ( 35.8%) 326 ( 32.8%) 828 ( 34.5%) 73 ( 22.5%) 412 ( 34.4%) 1313 ( 33.5%)

Group B 573 ( 40.8%) 428 ( 43.0%) 1001 ( 41.7%) 175 ( 53.8%) 499 ( 41.7%) 1675 ( 42.7%)

Group C 200 ( 14.3%) 148 ( 14.9%) 348 ( 14.5%) 35 ( 10.8%) 172 ( 14.4%) 555 ( 14.2%)

Group D 41 ( 2.9%) 26 ( 2.6%) 67 ( 2.8%) 14 ( 4.3%) 38 ( 3.2%) 119 ( 3.0%)

Group E 87 ( 6.2%) 67 ( 6.7%) 154 ( 6.4%) 28 ( 8.6%) 76 ( 6.3%) 258 ( 6.6%)



Yes 492 ( 35.1%) 357 ( 35.9%) 849 ( 35.4%) 129 ( 39.7%) 439 ( 36.7%) 1417 ( 36.1%)

No 911 ( 64.9%) 638 ( 64.1%) 1549 ( 64.6%) 196 ( 60.3%) 758 ( 63.3%) 2503 ( 63.9%)


Parent Study

Yes 1144 ( 81.5%) 928 ( 93.3%) 2072 ( 86.4%) 325 (100.0%) 1128 ( 94.2%) 3525 ( 89.9%)

No 259 ( 18.5%) 67 ( 6.7%) 326 ( 13.6%) 0 69 ( 5.8%) 395 ( 10.1%)


Parent Study

Yes 181 ( 12.9%) 180 ( 18.1%) 361 ( 15.1%) 8 ( 2.5%) 164 ( 13.7%) 533 ( 13.6%)

No 1222 ( 87.1%) 815 ( 81.9%) 2037 ( 84.9%) 317 ( 97.5%) 1033 ( 86.3%) 3387 ( 86.4%)

______________________________________________________________________________________________________________________________________________________










15



Table 3.1: Extent of Exposure to Study Drug

Safety Analysis Set


____________________________________________________________________________________________________________________________________________

Japan Subjects

______________________________________________________________________________


200 mg 100 mg Total Adalimumab Other

(N=87) (N=67) (N=154) (N=28) (N=76)

____________________________________________________________________________________________________________________________________________

Total Duration of Exposure to Study Drug (Weeks)

N 87 67 154 28 76

Mean (SD) 40.3 (16.00) 40.0 (17.29) 40.1 (16.52) 33.7 (13.87) 23.9 (10.64)

Median 38.7 38.9 38.8 32.2 24.0

Q1, Q3 29.6, 49.9 29.6, 50.1 29.6, 49.9 27.9, 47.9 14.2, 27.1

Min, Max 3.7, 79.7 2.4, 79.1 2.4, 79.7 8.4, 52.3 1.0, 52.1

Total Duration of Exposure to Study Drug (Years)

N 87 67 154 28 76

Mean (SD) 0.8 (0.31) 0.8 (0.33) 0.8 (0.32) 0.6 (0.27) 0.5 (0.20)

Median 0.7 0.7 0.7 0.6 0.5

Q1, Q3 0.6, 1.0 0.6, 1.0 0.6, 1.0 0.5, 0.9 0.3, 0.5

Min, Max 0.1, 1.5 0.0, 1.5 0.0, 1.5 0.2, 1.0 0.0, 1.0

Cumulative N (%) of Subjects Exposed to Study Drug

1 Day [Day 1] 87 (100.0%) 67 (100.0%) 154 (100.0%) 28 (100.0%) 76 (100.0%)

Week 12 [Day 85] 82 ( 94.3%) 65 ( 97.0%) 147 ( 95.5%) 27 ( 96.4%) 70 ( 92.1%)

Week 24 [Day 169] 78 ( 89.7%) 58 ( 86.6%) 136 ( 88.3%) 22 ( 78.6%) 31 ( 40.8%)

Week 36 [Day 253] 49 ( 56.3%) 37 ( 55.2%) 86 ( 55.8%) 10 ( 35.7%) 8 ( 10.5%)

Week 48 [Day 337] 24 ( 27.6%) 20 ( 29.9%) 44 ( 28.6%) 7 ( 25.0%) 3 ( 3.9%)

Week 52 [Day 365] 20 ( 23.0%) 15 ( 22.4%) 35 ( 22.7%) 6 ( 21.4%) 3 ( 3.9%)

Week 60 [Day 421] 13 ( 14.9%) 7 ( 10.4%) 20 ( 13.0%) 0 0

______________________________________________________________________________________________________________________________________________________



Duration of exposure to study drug (weeks) = (last dosing date - first dosing date + 1)/7

Duration of exposure to study drug (years) = (last dosing date - first dosing date + 1)/365.25

A 7-day window is applied to Week 52.


Source: .../wk24_japan/version1/prog/t-exp-drug.sas v9.4 Output file: t-exp-drug-rand.out 24MAY2019:22:51 Page 1 of 6

16




Safety Analysis Set


____________________________________________________________________________________________________________________________________________

Non-Japan Subjects

______________________________________________________________________________



(Continued) (N=1316) (N=928) (N=2244) (N=297) (N=1121)

____________________________________________________________________________________________________________________________________________


N 1316 928 2244 297 1121

Mean (SD) 55.3 (44.09) 42.6 (21.99) 50.1 (37.14) 40.4 (12.74) 25.8 (12.05)

Median 43.7 39.6 42.1 42.9 24.0

Q1, Q3 30.6, 63.4 24.3, 56.9 28.9, 60.9 33.1, 52.0 23.3, 28.6

Min, Max 0.7, 246.1 0.3, 194.9 0.3, 246.1 1.6, 53.4 0.3, 54.0


N 1316 928 2244 297 1121

Mean (SD) 1.1 (0.85) 0.8 (0.42) 1.0 (0.71) 0.8 (0.24) 0.5 (0.23)

Median 0.8 0.8 0.8 0.8 0.5

Q1, Q3 0.6, 1.2 0.5, 1.1 0.6, 1.2 0.6, 1.0 0.4, 0.5

Min, Max 0.0, 4.7 0.0, 3.7 0.0, 4.7 0.0, 1.0 0.0, 1.0


1 Day [Day 1] 1316 (100.0%) 928 (100.0%) 2244 (100.0%) 297 (100.0%) 1121 (100.0%)

Week 12 [Day 85] 1256 ( 95.4%) 887 ( 95.6%) 2143 ( 95.5%) 282 ( 94.9%) 968 ( 86.4%)

Week 24 [Day 169] 1162 ( 88.3%) 741 ( 79.8%) 1903 ( 84.8%) 267 ( 89.9%) 533 ( 47.5%)

Week 36 [Day 253] 841 ( 63.9%) 527 ( 56.8%) 1368 ( 61.0%) 203 ( 68.4%) 189 ( 16.9%)

Week 48 [Day 337] 549 ( 41.7%) 326 ( 35.1%) 875 ( 39.0%) 120 ( 40.4%) 109 ( 9.7%)

Week 52 [Day 365] 507 ( 38.5%) 298 ( 32.1%) 805 ( 35.9%) 111 ( 37.4%) 92 ( 8.2%)

Week 60 [Day 421] 376 ( 28.6%) 203 ( 21.9%) 579 ( 25.8%) 0 0

______________________________________________________________________________________________________________________________________________________








17




Safety Analysis Set


____________________________________________________________________________________________________________________________________________

Overall

______________________________________________________________________________



(Continued) (N=1403) (N=995) (N=2398) (N=325) (N=1197)

____________________________________________________________________________________________________________________________________________


N 1403 995 2398 325 1197

Mean (SD) 54.4 (43.04) 42.4 (21.71) 49.4 (36.25) 39.9 (12.96) 25.7 (11.97)

Median 43.6 39.6 42.0 42.0 24.0

Q1, Q3 30.1, 62.9 24.4, 56.7 28.9, 60.0 32.6, 52.0 23.3, 28.1

Min, Max 0.7, 246.1 0.3, 194.9 0.3, 246.1 1.6, 53.4 0.3, 54.0


N 1403 995 2398 325 1197

Mean (SD) 1.0 (0.82) 0.8 (0.42) 0.9 (0.69) 0.8 (0.25) 0.5 (0.23)

Median 0.8 0.8 0.8 0.8 0.5

Q1, Q3 0.6, 1.2 0.5, 1.1 0.6, 1.1 0.6, 1.0 0.4, 0.5

Min, Max 0.0, 4.7 0.0, 3.7 0.0, 4.7 0.0, 1.0 0.0, 1.0


1 Day [Day 1] 1403 (100.0%) 995 (100.0%) 2398 (100.0%) 325 (100.0%) 1197 (100.0%)

Week 12 [Day 85] 1338 ( 95.4%) 952 ( 95.7%) 2290 ( 95.5%) 309 ( 95.1%) 1038 ( 86.7%)

Week 24 [Day 169] 1240 ( 88.4%) 799 ( 80.3%) 2039 ( 85.0%) 289 ( 88.9%) 564 ( 47.1%)

Week 36 [Day 253] 890 ( 63.4%) 564 ( 56.7%) 1454 ( 60.6%) 213 ( 65.5%) 197 ( 16.5%)

Week 48 [Day 337] 573 ( 40.8%) 346 ( 34.8%) 919 ( 38.3%) 127 ( 39.1%) 112 ( 9.4%)

Week 52 [Day 365] 527 ( 37.6%) 313 ( 31.5%) 840 ( 35.0%) 117 ( 36.0%) 95 ( 7.9%)

Week 60 [Day 421] 389 ( 27.7%) 210 ( 21.1%) 599 ( 25.0%) 0 0

______________________________________________________________________________________________________________________________________________________








18




Safety Analysis Set


____________________________________________________________________________________________________________________________________________

Japan Subjects

______________________________________________________________________________



(N=87) (N=67) (N=154) (N=28) (N=76)

____________________________________________________________________________________________________________________________________________


Week 72 [Day 505] 4 ( 4.6%) 5 ( 7.5%) 9 ( 5.8%) 0 0

Week 84 [Day 589] 0 0 0 0 0

Week 96 [Day 673] 0 0 0 0 0

Week 108 [Day 757] 0 0 0 0 0

Week 120 [Day 841] 0 0 0 0 0

Week 132 [Day 925] 0 0 0 0 0

Week 144 [Day 1009] 0 0 0 0 0

Week 156 [Day 1093] 0 0 0 0 0

Week 168 [Day 1177] 0 0 0 0 0

Week 180 [Day 1261] 0 0 0 0 0

Week 192 [Day 1345] 0 0 0 0 0

Week 204 [Day 1429] 0 0 0 0 0

Week 216 [Day 1513] 0 0 0 0 0

Week 228 [Day 1597] 0 0 0 0 0

Week 240 [Day 1681] 0 0 0 0 0

______________________________________________________________________________________________________________________________________________________








19




Safety Analysis Set


____________________________________________________________________________________________________________________________________________

Non-Japan Subjects

______________________________________________________________________________



(Continued) (N=1316) (N=928) (N=2244) (N=297) (N=1121)

____________________________________________________________________________________________________________________________________________


Week 72 [Day 505] 225 ( 17.1%) 74 ( 8.0%) 299 ( 13.3%) 0 0

Week 84 [Day 589] 151 ( 11.5%) 33 ( 3.6%) 184 ( 8.2%) 0 0

Week 96 [Day 673] 120 ( 9.1%) 11 ( 1.2%) 131 ( 5.8%) 0 0

Week 108 [Day 757] 102 ( 7.8%) 4 ( 0.4%) 106 ( 4.7%) 0 0

Week 120 [Day 841] 99 ( 7.5%) 4 ( 0.4%) 103 ( 4.6%) 0 0

Week 132 [Day 925] 95 ( 7.2%) 3 ( 0.3%) 98 ( 4.4%) 0 0

Week 144 [Day 1009] 92 ( 7.0%) 3 ( 0.3%) 95 ( 4.2%) 0 0

Week 156 [Day 1093] 91 ( 6.9%) 3 ( 0.3%) 94 ( 4.2%) 0 0

Week 168 [Day 1177] 90 ( 6.8%) 2 ( 0.2%) 92 ( 4.1%) 0 0

Week 180 [Day 1261] 85 ( 6.5%) 2 ( 0.2%) 87 ( 3.9%) 0 0

Week 192 [Day 1345] 49 ( 3.7%) 1 ( 0.1%) 50 ( 2.2%) 0 0

Week 204 [Day 1429] 24 ( 1.8%) 0 24 ( 1.1%) 0 0

Week 216 [Day 1513] 11 ( 0.8%) 0 11 ( 0.5%) 0 0

Week 228 [Day 1597] 6 ( 0.5%) 0 6 ( 0.3%) 0 0

Week 240 [Day 1681] 1 (




Safety Analysis Set


____________________________________________________________________________________________________________________________________________

Overall

______________________________________________________________________________



(Continued) (N=1403) (N=995) (N=2398) (N=325) (N=1197)

____________________________________________________________________________________________________________________________________________


Week 72 [Day 505] 229 ( 16.3%) 79 ( 7.9%) 308 ( 12.8%) 0 0

Week 84 [Day 589] 151 ( 10.8%) 33 ( 3.3%) 184 ( 7.7%) 0 0

Week 96 [Day 673] 120 ( 8.6%) 11 ( 1.1%) 131 ( 5.5%) 0 0

Week 108 [Day 757] 102 ( 7.3%) 4 ( 0.4%) 106 ( 4.4%) 0 0

Week 120 [Day 841] 99 ( 7.1%) 4 ( 0.4%) 103 ( 4.3%) 0 0

Week 132 [Day 925] 95 ( 6.8%) 3 ( 0.3%) 98 ( 4.1%) 0 0

Week 144 [Day 1009] 92 ( 6.6%) 3 ( 0.3%) 95 ( 4.0%) 0 0

Week 156 [Day 1093] 91 ( 6.5%) 3 ( 0.3%) 94 ( 3.9%) 0 0

Week 168 [Day 1177] 90 ( 6.4%) 2 ( 0.2%) 92 ( 3.8%) 0 0

Week 180 [Day 1261] 85 ( 6.1%) 2 ( 0.2%) 87 ( 3.6%) 0 0

Week 192 [Day 1345] 49 ( 3.5%) 1 ( 0.1%) 50 ( 2.1%) 0 0

Week 204 [Day 1429] 24 (

gilead sciences, inc. safety analysis set...gilead sciences, inc. filgotinib ra j-iss week 24 table...

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