Joyce A Cramer1, Fulton F Velez2, Kathryn P Anastassopoulos3, T Christopher Bond4, Frank G Gilliam5, Philippe Ryvlin6, Luigi M Specchio7, Xuezhe Wang8, David Blum9, Joana Moreira10, Francisco Rocha11. 1. Department of Medical Research, Health Outcomes, Houston, TX, USA. Electronic address: joyce.cramer@gmail.com. 2. Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. Electronic address: Fulton.Velez@sunovion.com. 3. Covance Market Access Services Inc., Gaithersburg, MD, USA. Electronic address: Kathryn.Anastassopoulos@Covance.com. 4. Covance Market Access Services Inc., Gaithersburg, MD, USA. Electronic address: Christopher.Bond@Covance.com. 5. Department of Neurology, Penn State University College of Medicine, Hershey, PA, USA. Electronic address: fgilliam@hmc.psu.edu. 6. Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland. Electronic address: philipperyvlin@gmail.com. 7. Epilepsy Center, Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy. Electronic address: luigi.specchio@unifg.it. 8. Covance Market Access Services Inc., Gaithersburg, MD, USA. Electronic address: Xuezhe.Wang@Covance.com. 9. Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. Electronic address: David.Blum@sunovion.com. 10. BIAL - Portela & Cª S.A., S. Mamede do Coronado, Portugal. Electronic address: Joana.Moreira@bial.com. 11. BIAL - Portela & Cª S.A., S. Mamede do Coronado, Portugal. Electronic address: Francisco.rocha@bial.com.
Abstract
OBJECTIVE: The objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures. METHODS: The Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms. RESULTS: Out of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200 mg/day was significantly lower than that for placebo (2.68 vs 3.20, p<0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200 mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800 mg/day than for placebo; only SB was significant (p=0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p=0.006), DS (p=0.031), and SB (p=0.001). CONCLUSIONS: Therapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores. CLASSIFICATION OF EVIDENCE: This study presents Class I evidence that adjunctive ESL (800 and 1200 mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.
RCT Entities:
OBJECTIVE: The objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures. METHODS: The Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms. RESULTS: Out of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200 mg/day was significantly lower than that for placebo (2.68 vs 3.20, p<0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200 mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800 mg/day than for placebo; only SB was significant (p=0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p=0.006), DS (p=0.031), and SB (p=0.001). CONCLUSIONS: Therapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores. CLASSIFICATION OF EVIDENCE: This study presents Class I evidence that adjunctive ESL (800 and 1200 mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.