Table 3.
LS Mean (SE) changes from baseline in MDS-UPDRS Part IV subscores, item scores and CGI-C, mITT population and by baseline OFF time (MMRM).
| mITT (n = 196) | Baseline OFF ≥ 2.5 h (N = 102) | Baseline OFF < 2.5 h (N = 94) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Placebo (N = 96) | Amantadine-DR/ER (N = 100) | LS Mean [95% CI] Treatment difference | Placebo (N = 47) | Amantadine-DR/ER (N = 55) | LS Mean [95% CI] Treatment difference | Placebo (N = 49) | Amantadine-DR/ER (N = 45) | LS Mean [95% CI] Treatment difference | |
| Clinician’s Global Impression of Change (CGI-C) in Overall PD Symptoms at Week 12, n (%) | |||||||||
| Marked Improvement | 2 (2.1) | 28 (28.0) | – | 2 (4.3) | 17 (30.9) | – | 0 | 11 (24.4) | – |
| Moderate Improvement | 13 (13.5) | 29 (29.0) | – | 3 (6.4) | 14 (25.5) | – | 10 (20.4) | 15 (33.3) | – |
| Minimal Improvement | 21 (21.9) | 19 (19.0) | – | 11 (23.4) | 10 (18.2) | – | 10 (20.4) | 9 (20.0) | – |
| No Change | 40 (41.7) | 17 (17.0) | – | 20 (42.6) | 10 (18.2) | – | 20 (40.8) | 7 (15.6) | – |
| Minimal Worsening | 17 (17.7) | 4 (4.0) | – | 9 (19.1) | 2 (3.6) | – | 8 (16.3) | 2 (4.4) | – |
| Moderate Worsening | 3 (3.1) | 2 (2.0) | – | 2 (4.3) | 2 (3.6) | – | 1 (2.0) | 0 | – |
| P-value | p < 0.0001 | p < 0.0001 | p < 0.0001 | ||||||
| MDS-UPDRS Part IV subscores and item scores, change from baseline at Week 12; LS mean ± SE | |||||||||
| Part IV Total Score | −2.1 ± 0.3 | −4.4 ± 0.3 | − 2.3 [−3.2, −1.5] | −1.5 ± 0.4 | −4.2 ± 0.4 | −2.7 [−3.8, −1.6] | −2.6 ± 0.4 | −4.7 ± 0.5 | −2.1 [−3.4, −0.9] |
| Dyskinesia items (4.1 + 4.2) | −1.3 ± 0.2 | −2.6 ± 0.2 | −1.2 [−1.7, −0.7] | −1.1 ± 0.2 | −2.3 ± 0.2 | −1.2 [−1.9, −0.6] | −1.6 ± 0.3 | −2.9 ± 0.3 | −1.3 [−2.0, −0.5] |
| Motor fluctuations items (4.3 + 4.4 + 4.5 + 4.6) | −0.7 ± 0.2 | −1.8 ± 0.2 | −1.1 [−1.7, −0.4] | −0.3 ± 0.3 | −1.8 ± 0.3 | −1.5 [−2.2, −0.8] | −1.0 ± 0.4 | −1.8 ± 0.4 | −0.8 [−1.9, 0.3] |
| Item 4.1 (time spent with dyskinesia) | −0.6 ± 0.1 | −1.0 ± 0.1 | −0.5 [−0.8, −0.2] | −0.4 ± 0.1 | −0.8 ± 0.1 | −0.4 [−0.8, −0.1] | −0.7 ± 0.2 | −1.3 ± 0.2 | −0.6 [−1.0, −0.1] |
| Item 4.2 (functional impact of dyskinesia) | −0.8 ± 0.1 | −1.5 ± 0.1 | −0.8 [−1.0, −0.5] | −0.7 ± 0.2 | −1.5 ± 0.1 | −0.8 [−1.2, −0.4] | −0.9 ± 0.1 | −1.6 ± 0.2 | −0.7 [−1.2, −0.3] |
| Item 4.3 (time spent in the OFF state) | 0.0 ± 0.1 | −0.3 ± 0.1 | −0.3 [−0.5, −0.2] | 0.1 ± 0.1 | −0.3 ± 0.1 | −0.4 [−0.6, −0.2] | 0.0 ± 0.1 | −0.3 ± 0.1 | −0.3 [−0.5, −0.1] |
| Item 4.4 (functional impact of fluctuations) | −0.4 ± 0.1 | −0.8 ± 0.1 | −0.4 [−0.7, −0.1] | −0.3 ± 0.2 | −0.9 ± 0.2 | −0.6 [−1.0, −0.2] | −0.6 ± 0.2 | −0.8 ± 0.2 | −0.3 [−0.8, 0.2] |
| Item 4.5 (complexity of motor fluctuations) | −0.2 ± 0.1 | −0.3 ± 0.1 | −0.1 [−0.3, 0.2] | −0.1 ± 0.1 | −0.2 ± 0.1 | −0.1 [−0.4, 0.2] | −0.3 ± 0.2 | −0.3 ± 0.2 | −0.0 [−0.5, 0.4] |
| Item 4.6 (painful OFF-state dystonia) | −0.1 ± 0.1 | −0.4 ± 0.1 | −0.3 [−0.6, 0.0] | −0.1 ± 0.2 | −0.5 ± 0.1 | −0.4 [−0.8, −0.0] | −0.2 ± 0.1 | −0.5 ± 0.2 | −0.3 [−0.7, 0.1] |
p-values for CGI-C were calculated using the Cochran–Mantel–Haenszel mean score test using equally spaced scores. Treatment differences for MDS-UPDRS Part IV items are from the MMRM model with change from baseline as the dependent variable and baseline as a covariate, with categorical effects for treatment group, study, visit, and the interaction between treatment group and visit. mITT population.