Table 2.
Primary and secondary outcomesa
| Placebo (95% CI) |
Perampanel 4 mg (95% CI) |
Perampanel 8 mg (95% CI) |
Perampanel 4 mg vs. Placebo (95% CI) |
p value | Perampanel 8 mg vs. Placebo (95% CI) |
p value | |
|---|---|---|---|---|---|---|---|
| Primary outcome | |||||||
| Changes in ALSFRS-R score at 48 weeks from baseline | − 9.0 (− 13.1 to − 4.8) | − 13.4 (− 18.0 to − 8.8) | − 17.4 (− 22.7 to − 12.1) | − 4.5 (− 10.6 to 1.6) | 0.1476 | − 8.4 (− 15.0 to − 1.8) | 0.0145 |
| Number of patients at 48 weeks | 18 | 14 | 7 | ||||
| Secondary outcome | |||||||
| Changes in ALSFRS − R score at 48 weeks from baselineb | − 6.9 (− 10.9 to − 2.9) | − 9.4 (− 13.2 to − 5.7) | − 8.2 (− 12.3 to − 4.1) | − 2.5 (− 6.9 to 1.9) | 0.2574 | − 1.3 (− 5.6 to 3.0) | 0.5519 |
| Number of patients at 48 weeks | 22 | 20 | 21 | ||||
| Bulbar subscorec | − 0.8 (− 2.2 to 0.6) | − 2.2 (− 3.7 to − 0.6) | − 3.5 (− 5.3 to − 1.7) | − 1.4 (− 3.5 to 0.7) | 0.1760 | − 2.7 (− 5.0 to − 0.4) | 0.0206 |
| Upper limbs subscored | − 4.3 (− 5.8 to − 2.9) | − 4.2 (− 5.8 to − 2.6) | − 5.5 (− 7.4 to − 3.6) | 0.1 (− 1.9 to 2.2) | 0.8872 | − 1.2 (− 3.5 to 1.1) | 0.3028 |
| Lower limbs subscoree | − 3.1 (− 4.5 to − 1.7) | − 4.4 (− 5.9 to − 2.9) | − 4.3 (− 6.1 to − 2.6) | − 1.2 (− 3.2 to 0.7) | 0.2046 | − 1.2 (− 3.4 to 0.9) | 0.2583 |
| Respiratory subscoref | − 0.3 (− 1.3 to 0.8) | − 1.6 (− 2.8 to − 0.4) | − 1.6 (− 3.1 to − 0.1) | − 1.3 (− 2.9 to 0.3) | 0.1029 | − 1.4 (− 3.2 to 0.5) | 0.1375 |
| Total ALSFRS-R score at 48 weeksg | 30.7 (26.6 to 34.8) | 27.2 (22.8 to 31.7) | 23.6 (18.4 to 28.9) | − 3.5 (− 9.3 to 2.4) | 0.2351 | − 7.1 (− 13.5 to − 0.7) | 0.0315 |
| Changes in MMT grading at 48 weeks from baselineg | |||||||
| Biceps brachii (R) | − 1.4 (− 1.9 to − 0.8) | − 1.3 (− 1.9 to − 0.7) | − 0.8 (− 1.5 to − 0.1) | 0.1 (− 0.7 to 0.9) | 0.7924 | 0.6 (− 0.3 to 1.4) | 0.2006 |
| Biceps brachii (L) | − 1.2 (− 1.7 to − 0.7) | − 0.9 (− 1.4 to − 0.3) | − 1.4 (− 2.2 to 0.7) | 0.3 (− 0.4 to 1.1) | 0.3962 | − 0.3 (− 1.1 to 0.6) | 0.5425 |
| Triceps brachii (R) | − 0.9 (− 1.4 to − 0.3) | − 0.9 (− 1.5 to − 0.2) | − 0.7 (− 1.5 to 0.1) | 0.0 (− 0.8 to 0.8) | 0.9879 | 0.1 (− 0.8 to 1.1) | 0.7710 |
| Triceps brachii (L) | − 1.1 (− 1.6 to − 0.6) | − 0.8 (− 1.4 to − 0.3) | − 0.8 (− 1.5 to − 0.0) | 0.3 (− 0.4 to 1.0) | 0.3792 | 0.4 (− 0.4 to 1.2) | 0.3517 |
| Quadriceps femoris (R) | − 0.7 (− 1.3 to − 0.1) | − 0.6 (− 1.3 to 0.0) | − 1.2 (− 2.0 to − 0.4) | 0.1 (− 0.8 to 0.9) | 0.8432 | − 0.5 (− 1.5 to 0.5) | 0.3019 |
| Quadriceps femoris (L) | − 0.8 (− 1.4 to − 0.3) | − 0.5 (− 1.2 to 0.1) | − 0.8 (− 1.6 to 0.0) | 0.3 (− 0.5 to 1.1) | 0.483 | 0.0 (− 0.9 to 1.0) | 0.9802 |
| Hamstrings (R) | − 1.0 (− 1.5 to − 0.5) | − 0.5 (− 1.0 to 0.1) | − 0.2 (− 1.0 to 0.5) | 0.6 (− 0.2 to 1.3) | 0.1387 | 0.8 (− 0.1 to 1.6) | 0.0852 |
| Hamstrings (L) | − 1.0 (− 1.5 to − 0.5) | − 0.5 (− 1.0 to 0.0) | − 0.1 (− 0.7 to 0.6) | 0.5 (− 0.2 to 1.2) | 0.1417 | 0.9 (0.1 to 1.7) | 0.0216 |
| Sum score of MMT grading | − 8.3 (− 11.3 to − 5.4) | − 6.1 (− 9.4 to − 2.8) | − 6.5 (− 10.6 to − 2.4) | 2.2 (− 2.1 to 6.6) | 0.3098 | 1.8 (− 3.1 to 6.8) | 0.4574 |
| Changes in %FVC at 48 weeks from baseline | − 24.9 (− 35.3 to − 14.6) | − 31.4 (− 43.2 to − 19.6) | − 33.9 (− 48.5 to − 19.4) | − 6.4 (− 21.9 to 9.0) | 0.4027 | − 9.0 (− 26.5 to 8.5) | 0.3058 |
ALS amyotrophic lateral sclerosis, ALSFRS-R ALS functional rating scale-revised, MMT manual muscle testing
aAnalyses are based on data from the intention-to-treat population for all end points
bCovariance analysis was also used for the changes in ALSFRS-R score at 48 weeks from baseline
cBulbar subscore is sum of scores for items 1, 2, and 3 (speech, salivation, and swallowing) in ALSFRS-R
dUpper limb subscore is sum of scores for items 4, 5, and 6 (handwriting cutting food and handling utensils, and dressing and hygiene) in ALSFRS-R
eLower limb subscore is sum of scores for items 7, 8, and 9 (turning in bed and adjusting bed clothes, walking, and climbing stairs) in ALSFRS-R
fRespiratory subscore is sum of scores for items 10, 11, and 12 (dyspnea, orthopnea, and respiratory insufficiency) in ALSFRS-R
gNumber of patients at each week were the same as those in the total ALSFRS-R score