Table 2.
Summary of efficacy endpoints, full analysis set
| Placebo (n = 86) | SHP465 MAS | ||
|---|---|---|---|
| 12.5 mg/day (n = 89) | 37.5 mg/day (n = 88) | ||
| ADHD-RS-AP total score (primary endpoint) | |||
| Mean ± SD change from baseline at wk 4 | −11.0 ± 11.47 | −18.1 ± 13.42 | −23.8 ± 11.89 |
| LS mean ± SEM change from baseline at wk 4 | −10.4 ± 1.33 | −18.5 ± 1.31 | −23.8 ± 1.34 |
| LS mean (95% CI) treatment difference vs. placebo for change from baseline at wk 4a | −8.1 (−11.7, −4.4) | −13.4 (−17.1, −9.7) | |
| p value vs. placebob | p < 0.001 | p < 0.001 | |
| Effect sizec | 0.67 | 1.11 | |
| CGI-I score (key secondary endpoint) | |||
| Mean ± SD score at wk 4 | 3.1 ± 1.05 | 2.4 ± 1.16 | 1.9 ± 1.10 |
| LS mean ± SEM score at wk 4 | 3.1 ± 0.12 | 2.4 ± 0.12 | 1.9 ± 0.13 |
| LS mean (95% CI) treatment difference vs. placebo for CGI-I at wk 4a | −0.8 (−1.1, −0.4) | −1.2 (−1.6, −0.9) | |
| p value vs. placebob | p < 0.001 | p < 0.001 | |
| Effect sizec | 0.68 | 1.11 | |
| ADHD-RS-AP inattentiveness subscale score | |||
| Mean ± SD change from baseline at wk 4 | −6.1 ± 6.13 | −10.3 ± 7.59 | −13.8 ± 7.18 |
| LS mean ± SEM change from baseline at wk 4 | −5.7 ± 0.75 | −10.4 ± 0.74 | −13.8 ± 0.76 |
| LS mean (95% CI) treatment difference vs. placebo for change from baseline at wk 4a | −4.7 (−6.8, −2.6) | −8.1 (−10.2, −6.0) | |
| Nominal p value vs. placebob,d | p < 0.001 | p < 0.001 | |
| Effect sizec | 0.70 | 1.19 | |
| ADHD-RS-AP hyperactivity/impulsivity subscale score | |||
| Mean ± SD change from baseline at wk 4 | −4.9 ± 6.06 | −7.8 ± 6.89 | −9.9 ± 5.85 |
| LS mean ± SEM change from baseline at wk 4 | −4.7 ± 0.65 | −8.0 ± 0.65 | −10.0 ± 0.66 |
| LS mean (95% CI) treatment difference vs. placebo for change from baseline at wk 4a | −3.3 (−5.1, −1.5) | −5.3 (−7.2, −3.5) | |
| Nominal p value vs. placebob,d | p < 0.001 | p < 0.001 | |
| Effect sizec | 0.56 | 0.91 | |
ADHD-RS-AP Attention-Deficit/Hyperactivity Disorder Rating Scale with Adult Prompts, CGI-I Clinical Global Impressions-Improvement, CI confidence interval, LS least squares, MAS mixed amphetamine salts, SD standard deviation, SEM standard error of the mean
Sample size at wk 4 (placebo, n = 77; 12.5 mg/day of SHP465 MAS, n = 78; 37.5 mg/day of SHP465 MAS, n = 73)
aSHP465 MAS—placebo (negative value indicates a treatment effect favoring SHP465 MAS)
bBased on the mixed-effects model for repeated measures, including treatment, visit, and the interaction of treatment with the visit as factors; with the relevant baseline score as a covariate; and with an adjustment for the interaction of the baseline score with the visit
cDifference in the LS mean divided by the estimated SD from the unstructured covariance matrix
dNot included in the pre-specified fixed-sequence test procedure