Introduction
Methods
Study conduct
Study population
Study design
Study endpoints
Statistical analyses
Results
Study population
Opicapone 50 mg N = 126 | Levodopa 100 mg N = 118 | Total N = 244 | |
---|---|---|---|
Age, year | 64.1 (8.3) | 64.6 (9.1) | 64.3 (8.7) |
Male, n (%) | 65 (51.6) | 63 (52.9) | 128 (52.8) |
Hoehn and Yahr, stage | 2.0 (0.5) | 2.1 (0.5) | 2.0 (0.5) |
PD duration, year | 5.1 (3.6) | 5.3 (3.6) | 5.2 (3.6) |
MDS-UPDRS motor score | 23.7 (10.8) | 24.7 (11.5) | 24.2 (11.1) |
PDQ-8 summary index | 17.4 (13.2) | 18.4 (14.6) | 17.9 (13.9) |
Daily OFF time, h | 3.4 (1.0) | 3.4 (1.0) | 3.4 (1.0) |
Total ON time, h | 12.8 (1.6) | 12.8 (1.6) | 12.8 (1.6) |
ON time without dyskinesia, h | 11.6 (2.6) | 11.2 (3.3) | 11.4 (3.0) |
Levodopa dose at baseline, mg | 398.3 (117.4) | 412.4 (119.5) | 405.2 (118.7) |
Patients receiving 3 or 4 levodopa intakes per day, n (%)a | |||
3 intakes | 101 (80.2) | 93 (78.2) | 194 (79.5) |
4 intakes | 24 (19.0) | 25 (21.0) | 49 (20.1) |
Concomitant therapy, n (%)a | 106 (84.1) | 99 (83.9) | 205 (84.0) |
Dopamine agonist | 77 (61.1) | 75 (63.6) | 152 (62.3) |
Pramipexole | 56 (44.4) | 53 (44.9) | 109 (44.7) |
Rotigotine | 5 (4.0) | 5 (4.2) | 10 (4.1) |
Ropinirole | 22 (17.5) | 19 (16.1) | 41 (16.8) |
MAO-B inhibitor | 67 (53.2) | 67 (56.8) | 134 (54.9) |
Rasagiline | 59 (46.8) | 51 (43.2) | 110 (45.1) |
Safinamide | 7 (5.6) | 13 (11.0) | 20 (8.2) |
Selegiline | 2 (1.6) | 3 (2.5) | 5 (2.0) |
LEDDb, mg | 556.8 (166.5) | 575.6 (170.7) | 565.9 (168.5) |
Efficacy
Opicapone 50 mg N = 122 | Levodopa 100 mg N = 118 | |
---|---|---|
OFF time (min) | ||
LS mean (SE) change from baseline | − 62.8 (8.8) | − 33.8 (9.0) |
LS mean difference versus levodopa 100 mg (95% CI) | − 29.0 (− 53.8, − 4.2) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.0222 | |
Percent OFF time (%) | ||
LS mean (SE) change from baseline | − 6.5 (0.9) | − 3.7 (0.9) |
LS mean difference versus levodopa 100 mg (95% CI) | − 2.8 (− 5.4, − 0.3) | |
p-value for opicapone 50 mg versus levodopa 100 mg | 0.0309 | |
OFF-time responder rate (reduction of ≥ 1 h); n/N (%) | 69/122 (56.7%) | 54/116 (45.6%) |
Total ON time (min) | ||
LS mean (SE) change from baseline | 64.2 (10.3) | 43.8 (10.6) |
LS mean difference versus levodopa 100 mg (95% CI) | 20.4 (− 8.8, 49.6) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.1693 | |
ON time without dyskinesia (min) | ||
LS mean (SE) change from baseline | 54.9 (12.1) | 59.3 (12.4) |
LS mean difference versus levodopa 100 mg (95% CI) | − 4.4 (− 38.5, 29.7) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.8008 | |
ON time with troublesome dyskinesia (min) | ||
LS mean (SE) change from baseline | − 3.0 (6.2) | − 2.1 (6.4) |
LS mean difference versus levodopa 100 mg (95% CI) | − 0.9 (− 18.3, 16.6) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.9231 | |
Asleep (min) | ||
LS mean (SE) change from baseline | 0.9 (6.2) | − 10.1 (6.4) |
LS mean difference versus levodopa 100 mg (95% CI) | 10.9 (− 6.6, 28.4) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.2217 | |
MDS-UPDRS scores | ||
Part III | ||
LS mean (SE) change from baseline | − 4.1 (0.6) | − 2.5 (0.6) |
LS mean difference versus levodopa 100 mg (95% CI) | − 1.7 (− 3.3, − 0.04) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.0445 | |
Part IV | ||
LS mean (SE) change from baseline | − 1.1 (0.2) | − 0.8 (0.2) |
LS mean difference versus levodopa 100 mg (95% CI) | − 0.3 (− 0.7, 0.1) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.1734 | |
PDQ-8 summary index | ||
LS mean (SE) change from baseline | − 2.7 (1.0) | − 1.9 (1.0) |
LS mean difference versus levodopa 100 mg (95% CI) | − 0.9 (− 3.6, 1.9) | |
p value for opicapone 50 mg versus levodopa 100 mg | 0.5447 | |
Improvement on CGI-Ia, n/N (%) | 96/114 (84.2%) | 84/116 (72.4%) |
Improvement on PGI-Ia, n/N (%) | 90/113 (79.7%) | 80/116 (69.0%) |
Mean (SD) LEDD at end of study | 744.4b (218.5) | 664.9 (181.7) |
Safety
Opicapone 50 mg N = 125 | Levodopa 100 mg N = 118 | |
---|---|---|
Any AE, n (%) * | 47 (37.6) | 29 (24.6) |
Dyskinesia | 9 (7.2) | 5 (4.2) |
Dizziness | 8 (6.4) | 3 (2.5) |
Nausea | 3 (2.4) | 4 (3.4) |
Insomnia | 4 (3.2) | – |
Constipation | 4 (3.2) | 2 (1.7) |
Severity, n (%) | ||
Mild | 42 (33.6) | 24 (20.3) |
Moderate | 9 (7.2) | 6 (5.1) |
Severe | 1 (0.8) | 1 (0.8) |
Serious AEs, n (%) | 3 (2.4) | 2 (1.7) |
Spinal compression fracture | 2 (1.6) | – |
Subdural hematoma | 1 (0.8) | – |
Upper limb fracture | – | 1 (0.8) |
Retinal detachment | – | 1 (0.8) |
AEs leading to discontinuation, n (%) | 4 (3.2) | 2 (1.7) |
Vertigo | 1 (0.8) | – |
Somnolence | 1 (0.8) | – |
Tremor | 1 (0.8) | – |
Spinal compression fracture | 1 (0.8) | – |
Upper limb fracture | – | 1 (0.8) |
Dizziness | 1 (0.8) | – |
Insomnia | – | 1 (0.8) |
Rash | 1 (0.8) | – |
Any drug-related AE, n (%)a | 32 (25.6) | NAb |
Dyskinesia | 6 (4.8) | – |
Dizziness | 5 (4.0) | – |
Constipation | 4 (3.2) | – |
Insomnia | 4 (3.2) | – |
Headache | 3 (2.4) | – |
Nausea | 3 (2.4) | – |
Somnolence | 2 (1.6) | – |
Serious drug-related AE, n (%) | 1 (0.8) | – |
Subdural hematoma | 1 (0.8) | – |