TABLE 2.
Changes in patient-recorded functional status, UPDRS scores, overall clinical status, PDQ-39, and depression scores at endpoint
| Placebo (n = 222) | Safinamide 100 mg/day (n = 224) | Safinamide 50 mg/day (n = 223) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Parameter | Baseline | Change from baseline | Baseline | Change from baseline | P (vs placebo) | 95% CI | Baseline | Change from baseline | P (vs placebo) | 95% CI |
| Patient-recorded diary data | ||||||||||
| On time without dyskinesia, ha | 7.0 (3.33) | 0.6 (2.98) | 7.1 (3.50) | 1.1 (2.86) | 0.0103 | 0.2 to 1.1 | 7.1 (3.31) | 1.0 (3.24) | 0.0528 | −0.0 to 1.0 |
| On time with nontroublesome dyskinesia, ha | 2.3 (2.6) | 0.2 (1.92) | 2.4 (2.73) | 0.1 (2.07) | 0.4330 | −0.5 to 0.2 | 2.3 (2.52) | 0.2 (1.96) | 0.7897 | −0.4 to 0.3 |
| On time with troublesome dyskinesia, h | 1.0 (1.71) | −0.1 (1.48) | 0.7 (1.38) | 0.0 (1.78) | 0.6729 | −0.2 to 0.3 | 0.9 (1.73) | 0.0 (1.54) | 0.3259 | −0.1 to 0.4 |
| Off timeb, h | 5.30 (2.06) | −0.7 | 5.2 (2.16) | −1.3 | 0.0034 | −1.0 to −0.2 | 5.2 (2.08) | −1.3 | 0.0043 | −0.9 to −0.2 |
| Asleep, h | 2.4 (1.37) | 0.1 | 2.6 (1.38) | 0.0 | 0.6903 | −0.2 to 0.1 | 2.5 (1.25) | 0.0 | 0.6755 | −0.2 to 0.1 |
| Off time following first morning dose of levodopa, h | 4.8 (1.96) | −0.6 | 4.7 (2.07) | −1.2 | 0.0011 | −1.0 to −0.2 | 4.7 (2.0) | −1.1 | 0.0031 | −0.9 to −0.2 |
| Physician-related outcomes | ||||||||||
| UPDRS-III | 28.7 (12.02) | −4.3 | 28.3 (13.30) | −6.9 | 0.0006 | −4.1 to −1.1 | 27.3 (12.66) | −6.1 | 0.0138 | −3.3 to −0.4 |
| UPDRS-II | 12.3 (5.92) | −1.2 | 12.1 (5.82) | −2.2 | 0.0060 | −1.7 to −0.3 | 11.8 (5.66) | −1.7 | 0.1253 | −1.2 to 0.2 |
| CGI-C improvement, % patients | 55.4 | 64.3 | 0.0089 | 66.4 | 0.0010 | |||||
| CGI-S | 4.0 (0.66) | −0.2 | 4.0 (0.72) | −0.4 | 0.0448 | −0.2 to 0.0 | 4.0 (0.70) | −0.4 | 0.0060 | −0.3 to 0.0 |
| DRS score | 3.4 (3.93) | −0.2 (2.16) | 3.7 (4.07) | −0.3 (3.13) | 0.2431 | 3.9 (3.89) | −0.3 (2.52) | 0.1812 | ||
| Change in levodopa dose, % dose | −2.12 | −3.21 | 0.1092 | −1.41 | 0.1393 | |||||
| Patient-related outcomes | ||||||||||
| PDQ-39 | ||||||||||
| Total score | 230 (109.8) | −11.9 | 229 (124.1) | −28.4 | 0.0360 | −31.9 to −1.1 | 225 (110.5) | −16.4 | 0.5603 | −20.0 to 10.9 |
| Mobility | 41.8 (22.20) | −3.5 | 40.4 (25.81) | −5.5 | 0.2067 | −5.0 to 1.1 | 42.0 (23.24) | −5.9 | 0.1186 | −5.5 to 0.6 |
| Activities of daily living | 37.0 (21.85) | −1.5 | 36.5 (23.66) | −4.2 | 0.0940 | −5.7 to 0.5 | 37.0 (22.42) | −5.1 | 0.0256 | −6.6 to −0.4 |
| Emotional well-being | 30.4 (18.29) | −1.7 | 30.8 (18.86) | −5.1 | 0.0116 | −6.0 to −0.8 | 31.1 (19.70) | −2.4 | 0.6123 | −3.3 to 1.9 |
| Stigma | 31.4 (25.51) | −2.5 | 31.0 (26.16) | −2.9 | 0.8151 | −3.9 to 3.1 | 29.2 (25.66) | −3.9 | 0.4267 | −4.9 to 2.1 |
| Social support | 9.8 (16.70) | −0.2 | 11.2 (17.94) | 0.1 | 0.9684 | −2.8 to 2.7 | 9.5 (16.17) | 1.8 | 0.2498 | −1.1 to 4.3 |
| Cognition | 24.8 (17.58) | −0.5 | 23.7 (17.71) | −1.6 | 0.3775 | −3.6 to 1.3 | 22.6 (16.12) | 0.7 | 0.3081 | −1.2 to 3.7 |
| Communication | 25.9 (20.80) | −1.1 | 26.8 (22.33) | −4.4 | 0.0361 | −6.4 to −0.2 | 27.6 (20.90) | −2.6 | 0.3425 | −4.6 to 1.6 |
| Bodily discomfort | 28.8 (21.99) | 0.2 | 28.0 (21.43) | −3.5 | 0.0159 | −6.8 to −0.7 | 26.5 (20.06) | 1.3 | 0.4937 | −2.0 to 4.1 |
| GRID-HAM-D | ||||||||||
| Total score | 5.9 (3.70) | −0.3 | 6.0 (3.54) | −0.8 | 0.0731 | −1.0 to 0.0 | 6.0 (3.70) | −0.5 | 0.3922 | −0.8 to 0.3 |
Values are least square means (SD) unless otherwise stated.
The primary efficacy variable was the change in mean daily total on time with no dyskinesia plus mean daily total on time with nontroublesome dyskinesia (as used by Hauser et al.15).
Differences from placebo in off time (as for on time) were significant for both 50 and 100 mg/day doses from the first postbaseline evaluation (week 4) onward.
UPDRS, Unified Parkinson's Disease Rating Scale; PDQ-39, Parkinson's disease questionnaire; CI, confidence interval; on, on medication; off, off medication; UPDRS-III, UPDRS motor scale, UPDRS-II, UPDRS self-evaluation of the activities of daily life; CGI-C, Clinical Global Impression-Change; CGI-S, Clinical Global Impression-Severity; DRS, dyskinesia rating scale; GRID-HAM-D, GRID-Hamilton Rating Scale for Depression.