Table 1.
Summary of Phase II and Phase III clinical trials with retigabine
| Phase II | Phase III | ||
|---|---|---|---|
| Study 205 | Study 301 (RESTORE 1) | Study 302 (RESTORE 2) | |
| Patients | Age: 16–70 years Gender: men and women Clinical features: partial onset epilepsy (≥4 seizures/month; no 30-day seizure-free period in the baseline period) Concomitant therapy: 1–2 standard AEDs (VP, CMZ, PHT, TPR, LMT, GBP); VNS |
Age: 18–75 years Gender: men and women Clinical features: partial onset epilepsy (≥4 seizures/month; no 21-day seizure-free period in the baseline period) Concomitant therapy: 1–3 standard AEDs (VP, CMZ, PHT, TPR, LMT, GBP); VNS |
Age: 18–75 years Gender: men and women Clinical features: partial onset epilepsy (≥4 seizures/month; no 21-day seizure-free period in the baseline period) Concomitant therapy: 1–3 standard AEDs (VP, CMZ, PHT, TPR, LMT, GBP); VNS |
| Patients (n) | 396 | 256 | 471 |
| Dose of RT | 1200 mg/day (400 mg tid) 900 mg/day (300 mg tid) 600 mg/day (200 mg tid) No change of dose allowed |
1200 mg/day (400 mg tid) Dose reduction allowed (to 1050 mg/day) |
900 mg/day (300 mg tid) 600 mg/day (200 mg tid) No change of dose allowed |
| Study design | 8-week baseline period 8-week forced titration period 8-week maintenance period |
8-week baseline period 6-week forced titration period 12-week maintenance period |
8-week baseline period 4-week forced titration period 12-week maintenance period |
| Median seizure frequency reduction | 23% in 600 mg/day RT arm* 29% in 900 mg/day RT arm 35% in 1200 mg/day RT arm 13% in placebo arm |
44% in RT arm 17.5% in placebo arm |
27.9% in 600 mg/day RT arm 39.9% in 900 mg/day RT arm 17.5% in placebo arm |
| Responders rate | 23% in 600 mg/day RT arm 32% in 900 mg/day RT arm 33% in 1200 mg/day RT arm 16% in placebo arm |
45% in RT arm 18% in placebo arm |
31.5% in 600 mg/day RT arm 39.3% in 900 mg/day RT arm 17.3% in placebo arm |
| Adverse events | Somnolence, confusion, dizziness, headache, asthenia | Somnolence, dizziness, headache, confusion, asthenia | Somnolence, dizziness, headache, confusion, asthenia |
| Open-label extension | Number of patients: 222 RT dose: 900 mg/day (up to 1200 mg/day) Median seizure frequency reduction: 48.3% Responders rate: 46.4% AE: somnolence, confusion, dizziness, headache, asthenia |
Number of patients: 181 RT dose: 600–1200 mg/day (mean dose 1052 mg/day); modification of dose (of RT and other AEDs) allowed Duration: 357 days (trial ongoing) Median seizure frequency reduction: 57% Responders rate: 57% Seizure frequency reduction >75%: 29.6% 6-month seizure free period: 10% AE: dizziness, somnolence, urinary or renal disorders, headache |
Number of patients: 375 RT dose: 600–1200 mg/day (mean dose 861 mg/day); modification of dose (of RT and other AEDs) allowed Duration: 275 days (trial ongoing) Median seizure frequency reduction: 53% Responders rate: 54% Seizure frequency reduction >75%: 24% 6-month seizure free period: 8% AE: dizziness, somnolence, headache, asthenia |
*
Note: Not statistically different versus placebo.
Abbreviations: AE, adverse events; RT, retigabine; VP, valproate; CMZ, carbamazepine; PHT, phenytoin; TPR, topiramate; LMT, lamotrigine; GBP, gabapentin; VNS, vagal nerve stimulation.