h the primary efficacy analysis (change from baseline at Week 6 on the ADHD-RS Total score) and the key secondary efficacy analysis (at last study visit on the CGI-I) (see Table 2).
Table 2: Change from Baseline on ADHD-RS-IV Total Score and Endpoint on CGI-I (Full Analysis Set)
SPD489- 405
Primary at Week 8 ADHD-RS-IV
Placebo
SPD489
OROS-
MPH
Baseline Total Score
N
Mean (SE)
89
38.2 (0.73)
179
36.6 (0.48)
184
37.8 (0.45)
Change from baseline at Week 8
N
LS Mean (SE) [a]
67
-13.4
(1.19)
139
-25.6
(0.82)
152
-23.5 (0.80)
Lisdexamfetamine vs OROS-MPH difference
LS Mean (SE) [a]
(95% CI) [a]
Effect size [b] p-value
NA
-2.1 (1.15)
-4.3, 0.2
0.2
0.0717
NA
Active vs Placebo difference
LS Mean (SE) [a]
(95% CI) [a]
Effect size [b] p-value
NA
-12.2
(1.45)
-15.1, -9.4
1.16
<0.0001
-10.1 (1.43)
-13.0, -7.3
0.97
<0.0001
Key Secondary Endpoint CGI-I
Subjects analysed (n)
89
178
184
Improved (%) [c]
Not improved (%) [d]
31 (34.8)
58 (65.2)
148 (83.1)
30 (16.9)
149 (81.0)
35 (19.0)
Lisdexamfetamine vs OROS-MPH [e]
Active treatment vs Placebo [e]
NA
NA
0.6165
<0.0001
NA
<0.0001
SPD489- 406
Primary at Week 6 ADHD-RS-IV
Placebo
SPD489
OROS-
MPH
Baseline Total Score
N
Mean (SE)
106
36.1 (0.58)
210
37.3 (0.44)
216
37.0 (0.44)
Change from baseline at Week 6
N
LS Mean (SE) [a]
93
-17.0
(1.03)
175
-25.4
(0.74)
181
-22.1 (0.73)
Lisdexamfetamine vs OROS-MPH difference
LS Mean (SE) [a]
(95% CI) [a]
Effect size [b] p-value
NA
-3.4 (1.04)
-5.4, -1.3
0.33
0.0013
NA
Active vs Placebo difference
LS Mean (SE) [a]
(95% CI) [a]
Effect size [b] p-value
NA
-8.5 (1.27)
-11.0, -6.0
0.82
<0.0001
-5.1 (1.27)
-7.6, -2.6
0.50
<0.0001
Key Secondary Endpoint CGI-I
Subjects analysed (n)
106
210
216
Improved (%) [c]
Not improved (%) [d]
53 (50.0)
53 (50.0)
171 (81.4)
39 (18.6)
154 (71.3)
62 (28.7)
Lisdexamfetamine vs OROS-MPH [e]
Active treatment vs Placebo [e]
NA
NA
0.0188
<0.0001
NA
0.0002
[a] From a mixed effects model for repeated measures (MMRM) that includes treatment group, nominal visit, interaction of the treatment group with the visit as factors, baseline ADHD-RS-IV total score as a covariate, and an adjustment for the interaction of the baseline ADHD-RS-IV total score with the visit. The model is based on a REML method of estimation and utilizes an unstructured covariance type.
[b] The effect size is the difference in LS mean divided by the estimated standard deviation from the unstructured covariance matrix.
[c] The 'Improved' category includes responses of 'Very much improved' and 'Much improved'.
[d] The 'Not improved' category includes responses of 'Minimally improved', 'No change', 'Minimally worse', 'Much worse' and 'Very much worse'.
[e] From a CMH test stratified by baseline CGI-S.
Note: N = number of subjects in each treatment group, n = number of subjects analysed.
A 2-year open label safety study conducted in children and adolescents (ages 6-17) with ADHD enrolled 314 patients. Of these, 191 patients completed the study.
Maintenance of effect was demonstrated in a double-blind, placebo-controlled, randomised withdrawal study conducted in children and adolescents ages 6 to 17 (n=157) who met the d |
