Adenuric (febuxostat) - Tabell I-V
Tabell I. Andel patienter i APEX-studien vilkas senaste tre serumuratnivåer var < 360 mikromol/L (˜ 6 mg/dL)
|
Last 3 Serum Urate Levels < 6 mg/dL |
Placebo
n/N % |
Febuxostat
80 mg QD
n/N % |
Febuxostat
120 mg QD
n/N % |
Febuxostat
240 mg QD
n/N % |
Allopurinol
300/100 mg QD
n/N % |
|
Yes |
0/134 (0 %) |
126/262 (48 %) |
175/269 (65 %) |
92/134 (69 %) |
60/268 (22 %) |
|
No |
134/134 (100 %) |
136/262 (52 %) |
94/269 (35 %) |
42/134 (31 %) |
208/268 (78 %) |
|
|
Difference in Proportions |
97,5 % CI |
P-value |
|
Febuxostat 80 mg vs. Allopurinol 300/100 mg |
26 % |
(16,7 %, 34,7%) |
< 0,001 |
|
Febuxostat 120 mg vs. Allopurinol 300/100 mg |
43 % |
(34,0 %, 51,3 %) |
< 0,001 |
Tabell II. Resultat av sekundära effektparametrar i APEX-studien.
10 mg/dL ˜ 600 mikromol/L, 9 mg/dL ˜ 540 mikromol/L, 6 mg/dL ˜ 360 mikromol/L, 5 mg/dL ˜ 300 mikromol/L, 4 mg/dL ˜ 240 mikromol/L.
|
Secondary endpoints |
Placebo
n/N (%)
|
Febuxostat
(80 mg/d)
n/N (%)
|
Febuxostat
(120 mg/d)
n/N (%)
|
Febuxostat
(240 mg/d)
n/N (%) |
Allopurinol
(300/100 mg/d)
n/N (%) |
|
Proportion of pat. with sUA at wk 28(x)
< 6 mg/dL
< 5 mg/dL
< 4 mg/dL |
1/99 (1 %)
0 %
0 % |
122/161(76 %)
51 %
21 % |
163/188 (87 %)
72 %
41 % |
78/83 (94 %)
87 %
78 % |
85/208 (41 %)
13 %
2 % |
|
Proportion of pat. with sUA
at final visit (x) < 6mg/dL
< 5 mg/dL
< 4mg/dL |
1/127 (1 %)
0 %
0 % |
183/253(72 %)
46 %
18 % |
209/265 (79 %)
65 %
38 % |
116/126(92 %)
84 %
75 % |
102/263 (39 %)
13 %
2 % |
|
Serum urate concentration: Baseline mean ± SD (mg/dL)
% change from baseline at final visit (y) |
9,8 ± 1,36
-2,99 ± 13,3 |
9,96 ± 1,33
-45,2 ± 18,2 |
9,88 ± 1,22
-51,9 ± 18,0 |
9,81 ± 1,19
-66,3 ± 20,6 |
9,78 ± 1,21
-33,7 ± 14,7 |
|
Proportion of pat. with sUA < 6 mg/dL at last visit according to baseline conc.
Baseline < 9 mg/dL
Baseline 9 to 10 mg/dL
Baseline > 10 mg/dL |
1/32 (3 %)
0/50 (0 %)
0/45(0 %) |
56/61 (92 %)
65/89 (73 %)
62/103 (60 %) |
66/74 (89 %)
66/78 (85 %)
77/113 (68 %) |
30/31 (97 %)
43/46 (93 %)
43/49 (88 %) |
44/79 (56 %)
39/95 (41 %)
19/89 (21 %) |
|
Subjects requiring treatment for gout flares:
Screening
Day 1 to wk 8 (prophylaxis)
Wk 8–12
Wk 12–16
Wk 24–28
Wk 8–28 |
12/134 (9 %)
27/134 (20 %)
34/118 (29 %)
23/112 (21 %)
21/103 (20%)
62/119 (52 %) |
21/262 (8 %)
73/262 (28 %)
79/223 (35 %)
47/206 (23 %)
26/172 (15 %)
122/223 (55 %) |
28/269 (10 %)
97/269 (36 %)
97/240 (40 %)
47/227 (21 %)
30/206 (15 %)
129/240 (54 %) |
13/134 (10 %)
61/134 (46 %)
45/106 (42 %)
15/99 (15 %)
7/89 (8 %)
60/106 (57 %) |
20/268 (7 %)
61/268 (23 %)
63/237 (27 %)
51/227 (22 %)
31/216 (14 %)
110/237 (46 %) |
|
Tophus size changes from baseline (median) at wk 28
at final visit
Nr of patients (change in nr of tophi per patient, median %) |
21 (-52 %)
26 (-40,3 %)
22 (0) wk 28
-0.3
|
26 (-45,6 %)
42 (-33,8 %)
28 (0) wk 28
-0,3 |
35 (-54,2 %)
50 (-42,4 %)
38 (0) wk 28
-1,2 |
14 (-53,2 %)
24 (-47,0 %)
16 (0) wk 28
-0,4 |
46 (-31,5 %)
61 (-22,6 %)
47 (0) wk 28
-0,4 |
Tabell III. Andel studiepatienter i FACT-studien vilkas senaste tre serumurinsyravärden var < ˜ 360 mikromol/L.
|
Last 3 Serum Urate Levels < 6 mg/dL |
Febuxostat
80 mg QD
n/N % |
Febuxostat
120 mg QD
n/N % |
Allopurinol
300 mg QD
n/N % |
|
Yes |
136/255 (53 %) |
154/250 (62 %) |
53/251 (21 %) |
|
No |
119/255 (47 %) |
96/250 (38 %) |
198/251 (79 %) |
|
|
Difference in Proportions |
97,5 % CI |
P-value |
|
Febuxostat 80 mg vs. Allopurinol |
32 % |
(23,1 %, 41,3 %) |
< 0,001 |
|
Febuxostat 120 mg vs. Allopurinol |
41 % |
(31,5%, 49,5%) |
< 0,001 |
Tabell IV. Sekundära effektparametrar i FACT-studien.
10 mg/dL ˜ 600 mikromol/l, 9 mg/dL ˜ 540 mikromol/L, 6 mg/dL ˜ 360 mikromol/L, 5 mg/dL ˜ 300 mikromol/L, 4 mg/dL ˜ 240 mikromol/L
|
Secondary endpoints |
Febuxostat
(80 mg/d)
n/N (%)
|
Febuxostat
(120 mg/d)
n/N (%) |
Allopurinol
(300 mg/d)
n/N (%) |
|
Proportion of Patients with sUA at wk 52
< 6mg/dL
< 5mg/dL
< 4mg/dL |
129/159 (81 %)
55 %
23 % |
119/145 (82 %)
71 %
45 % |
70/178 (39 %)
15 %
2 % |
|
Proportion of Patients with sUA at final visit
< 6mg/dL
< 5mg/dL
< 4mg/dL |
185/249 (74 %)
47 %
20 % |
193/242 (80 %)
66 %
41 % |
88/242 (36 %)
13 %
2 %
|
|
Percent change in sUA concentration from baseline at final visit (Mean ± SD) Wk 28
Wk 52
Final visit
|
-46,3 ± 15,8
-47,7 ± 17,5
-44,7 ± 19,1 |
-53,5 ± 18,2
-53,0 ± 19,3
-51,5 ± 19,9 |
-34,8 ± 12,9
-34,8 ± 13,5
-33,0 ± 15,3 |
|
Proportion of Patients with sUA< 6 mg/dL at last visit according to baseline conc.
Baseline < 9 mg/dL
Baseline 9 to 10 mg/dL
Baseline > 10 mg/dL |
58/71 (82 %)
57/74 (77 %)
70/104 (67 %) |
58/67 (87 %)
73/79 (92 %)
62/96 (65 %) |
35/61 (57 %)
31/78 (40 %)
22/103 (21 %) |
|
Subjects requiring treatment for gout flares
Screening
Day 1–wk 8 (prophylaxis)
Wk 8–16
Wk 16–24
Wk 48–52
Wk 8–52 |
20/255 (8 %)
55/255 (22 %)
110/228 (48 %)
75/210 (36 %)
13/167 (8 %)
147/228 (64 %) |
28/250 (11 %)
90/250 (36 %)
115/215 (53 %)
69/191 (36 %)
9/153 (6 %)1
150/215 (70 %)
9/191
|
20/251 (8 %)
52/251 (21 %)
101/234( 43 %)
67/216 (31 %)
20/185 (11 %)
150/234 (64 %) |
|
Tophus changes from baseline at wk 52
No. of patients (median % change in area)
No. of patients (median % change in no. of
tophi/patient)
|
32 (-83)
33 (0)
|
26 (-66)
28 (-1)
|
30 (-50)
35 (0) |
Tabell V. Patienter med primära prövarrapporterade kardiovaskulära händelser i de pivotala fas III-studierna.
|
Primary APTC
Events |
Placebo
(n = 134)
PY – 59,9 |
Febuxostat total
(n = 1177)
PY – 671,1 |
Febuxostat
80 mg
(n = 523)
PY – 322,6 |
Febuxostat
120 mg
(n = 520)
PY – 304,5 |
Febuxostat
240 mg
(n = 134)
PY – 54,0 |
Allopurinol
(300/100 mg)
(n = 521)
PY – 333,7 |
|
|
|
n (RPY) |
n (RPY) |
n (RPY) |
n (RPY) |
n (RPY) |
|
Overall |
0 |
9 (1,30) |
4 (1,30) |
5 (1,6) |
0 |
1 (0,3) |
|
Cardiovascular death |
0 |
3 (0,4) |
2 (0,6) |
1 (0,30) |
0 |
0 |
|
Non-fatal myocardial infarction |
0 |
5 (0,7) |
2 (0,6) |
3 (1) |
0 |
1 (0,3) |
|
Non-fatal stroke |
0 |
1 (0,1) |
0 |
1 (0,1) |
0 |
0 |
|
Non-fatal cardiac arrest |
0 |
1 (0,1) |
0 |
1 (0,3) |
0 |
0 |
Abbrevations: The percentages are the rate per 100 patient-years of exposure; N, number of patients dosed; PY, total patient-year of exposure.