Jacqueline French1, Patrick Kwan, Toufic Fakhoury, Verne Pitman, Sarah DuBrava, Lloyd Knapp, Lorraine Yurkewicz. 1. From the NYU Comprehensive Epilepsy Center (J.F.), New York, NY; Departments of Medicine and Neurology (P.K.), University of Melbourne, Royal Melbourne Hospital, Australia; Department of Medicine and Therapeutics (P.K.), Chinese University of Hong Kong, China; St. Joseph Health System (T.F.), Lexington, KY; and Pfizer Inc. (V.P., S.D., L.K., L.Y.), New York, NY.
Abstract
OBJECTIVE: To assess pregabalin monotherapy for partial-onset seizures using a historical-controlled conversion-to-monotherapy design. METHODS:Adults with inadequately controlled partial-onset seizures while receiving 1 or 2 antiepileptic drugs during an 8-week prospective baseline were randomized to double-blind monotherapy with pregabalin 600 or 150 mg/d (4:1) for 20 weeks (8-week conversion and 12-week monotherapy period). The primary endpoint was the seizure-related exit rate for pregabalin 600 mg/d, based on discontinuations due to predefined criteria. Efficacy was declared if the upper limit of the 95% confidence interval for the exit rate was below a historical-control threshold of 74%, with stepwise evaluation using a threshold of 68%. RESULTS: The trial was stopped early for positive efficacy after an interim analysis in 125 patients. The full study population included 161 patients, with 148 evaluable for efficacy. The mean time since epilepsy diagnosis was 14 years. Overall, 54.3% (600 mg/d) and 46.9% (150 mg/d) of patients completed 20 weeks of double-blind treatment. Seizure-related exit rate in the 600 mg/d group (27.5%; 95% confidence interval, 17.8%-37.2%) was significantly below the 74% and 68% thresholds (p < 0.001 for both). Eight patients on 600 mg/d and 2 on 150 mg/d were seizure-free throughout pregabalin monotherapy. Pregabalin's overall safety profile was consistent with prior trials. CONCLUSIONS:Pregabalin monotherapy was safe and efficacious for patients with inadequately controlled partial-onset seizures. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with inadequately controlled partial-onset seizures switched topregabalin monotherapy have fewer seizure-related exit events compared with historical controls switched to pseudo-placebo monotherapy.
RCT Entities:
OBJECTIVE: To assess pregabalin monotherapy for partial-onset seizures using a historical-controlled conversion-to-monotherapy design. METHODS: Adults with inadequately controlled partial-onset seizures while receiving 1 or 2 antiepileptic drugs during an 8-week prospective baseline were randomized to double-blind monotherapy with pregabalin 600 or 150 mg/d (4:1) for 20 weeks (8-week conversion and 12-week monotherapy period). The primary endpoint was the seizure-related exit rate for pregabalin 600 mg/d, based on discontinuations due to predefined criteria. Efficacy was declared if the upper limit of the 95% confidence interval for the exit rate was below a historical-control threshold of 74%, with stepwise evaluation using a threshold of 68%. RESULTS: The trial was stopped early for positive efficacy after an interim analysis in 125 patients. The full study population included 161 patients, with 148 evaluable for efficacy. The mean time since epilepsy diagnosis was 14 years. Overall, 54.3% (600 mg/d) and 46.9% (150 mg/d) of patients completed 20 weeks of double-blind treatment. Seizure-related exit rate in the 600 mg/d group (27.5%; 95% confidence interval, 17.8%-37.2%) was significantly below the 74% and 68% thresholds (p < 0.001 for both). Eight patients on 600 mg/d and 2 on 150 mg/d were seizure-free throughout pregabalin monotherapy. Pregabalin's overall safety profile was consistent with prior trials. CONCLUSIONS:Pregabalin monotherapy was safe and efficacious for patients with inadequately controlled partial-onset seizures. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with inadequately controlled partial-onset seizures switched to pregabalin monotherapy have fewer seizure-related exit events compared with historical controls switched to pseudo-placebo monotherapy.
Authors: Jacqueline A French; Nancy R Temkin; Bassel F Shneker; Anne E Hammer; Paul T Caldwell; John A Messenheimer Journal: Neurotherapeutics Date: 2012-01 Impact factor: 7.620
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