Christian Brandt1, Pavel Klein2, Vincent Badalamenti3, Teresa Gasalla4, John Whitesides5. 1. Bethel Epilepsy Centre, Mara Hospital, Maraweg 21, 33617 Bielefeld, Germany. Electronic address: Christian.brandt@mara.de. 2. Mid-Atlantic Epilepsy and Sleep Center, Champlain Building, 6410 Rockledge Drive #610, Bethesda, MD 20817, USA. Electronic address: kleinp@epilepsydc.com. 3. UCB Pharma, 8010 Arco Corporate Drive, Raleigh, NC 27617, USA. Electronic address: vcbadalamenti@aol.com. 4. UCB Pharma, 8010 Arco Corporate Drive, Raleigh, NC 27617, USA. Electronic address: Teresa.Gasalla@ucb.com. 5. UCB Pharma, 8010 Arco Corporate Drive, Raleigh, NC 27617, USA. Electronic address: John.Whitesides@ucb.com.
Abstract
OBJECTIVE: The objective of this analysis was to provide a comprehensive analysis of safety data for adjunctive brivaracetam (BRV), an antiepileptic drug (AED) of the racetam class, for treatment of focal seizures in patients with epilepsy. METHODS: Data were pooled from two phase II, placebo-controlled, double-blind, dose-ranging trials (N01114 [ClinicalTrials.gov: NCT00175929], N01193 [NCT00175825]) and three phase III, placebo-controlled, double-blind, 12-week trials (N01252 [NCT00490035], N01253 [NCT00464269], and N01358 [NCT01261325]) in patients aged ≥16 years with focal seizures, as well as a phase III, placebo-controlled, double-blind, 16-week trial in patients aged ≥16 years with focal or generalized epilepsy (N01254 [NCT00504881]). Data are presented for the approved therapeutic dose range of 50-200 mg/day. Data for BRV administered intravenously (25-150 mg doses) were pooled separately from one phase III trial (N01258 NCT01405508]) and two clinical pharmacology trials (N01256 [Part B] [UCB Pharma, data on file]; EP0007 [NCT01796899]). Adverse events (AEs) of interest were summarized in relevant categories. RESULTS: The safety pool comprised 1957 patients: 1271 receiving adjunctive BRV and 686 receivingplacebo. Overall, the incidence of treatment-emergent adverse events (TEAEs) was 66.9% with BRV versus 62.8% with placebo. The most frequently reported TEAEs with BRV (≥5% of patients) versus placebo were somnolence (13.3% vs. 7.9%), headache (10.5% vs. 11.5%), dizziness (10.0% vs. 7.0%), and fatigue (8.2% vs. 4.2%). Incidence of psychiatric disorder-related TEAEs was 11.3% with BRV versus 8.2% with placebo. Behavioral disorder-related TEAE incidence was low (4.0% with BRV vs. 2.5% with placebo). Irritability was reported in 2.7% of BRV-treated patients vs. 1.5% of patients receiving placebo; anger, aggression, and agitation were each reported by ≤1% of patients receiving BRV. Treatment-emergent adverse events potentially associated with psychosis were psychotic disorder (three patients on BRV vs. two patients on placebo), auditory hallucination, illusion, visual hallucination (one patient each on BRV), epileptic psychosis, and hallucination (one patient each on placebo). No additional safety concerns were identified in patients with intravenous (IV) BRV administration (n = 104). CONCLUSIONS: These safety data for adjunctive BRV support its acceptable safety and tolerability profile.
RCT Entities:
OBJECTIVE: The objective of this analysis was to provide a comprehensive analysis of safety data for adjunctive brivaracetam (BRV), an antiepileptic drug (AED) of the racetam class, for treatment of focal seizures in patients with epilepsy. METHODS: Data were pooled from two phase II, placebo-controlled, double-blind, dose-ranging trials (N01114 [ClinicalTrials.gov: NCT00175929], N01193 [NCT00175825]) and three phase III, placebo-controlled, double-blind, 12-week trials (N01252 [NCT00490035], N01253 [NCT00464269], and N01358 [NCT01261325]) in patients aged ≥16 years with focal seizures, as well as a phase III, placebo-controlled, double-blind, 16-week trial in patients aged ≥16 years with focal or generalized epilepsy (N01254 [NCT00504881]). Data are presented for the approved therapeutic dose range of 50-200 mg/day. Data for BRV administered intravenously (25-150 mg doses) were pooled separately from one phase III trial (N01258 NCT01405508]) and two clinical pharmacology trials (N01256 [Part B] [UCB Pharma, data on file]; EP0007 [NCT01796899]). Adverse events (AEs) of interest were summarized in relevant categories. RESULTS: The safety pool comprised 1957 patients: 1271 receiving adjunctive BRV and 686 receiving placebo. Overall, the incidence of treatment-emergent adverse events (TEAEs) was 66.9% with BRV versus 62.8% with placebo. The most frequently reported TEAEs with BRV (≥5% of patients) versus placebo were somnolence (13.3% vs. 7.9%), headache (10.5% vs. 11.5%), dizziness (10.0% vs. 7.0%), and fatigue (8.2% vs. 4.2%). Incidence of psychiatric disorder-related TEAEs was 11.3% with BRV versus 8.2% with placebo. Behavioral disorder-related TEAE incidence was low (4.0% with BRV vs. 2.5% with placebo). Irritability was reported in 2.7% of BRV-treated patients vs. 1.5% of patients receiving placebo; anger, aggression, and agitation were each reported by ≤1% of patients receiving BRV. Treatment-emergent adverse events potentially associated with psychosis were psychotic disorder (three patients on BRV vs. two patients on placebo), auditory hallucination, illusion, visual hallucination (one patient each on BRV), epileptic psychosis, and hallucination (one patient each on placebo). No additional safety concerns were identified in patients with intravenous (IV) BRV administration (n = 104). CONCLUSIONS: These safety data for adjunctive BRV support its acceptable safety and tolerability profile.
Authors: Mark Kristof Farkas; Harriet Kang; Andras Fogarasi; Ali Bozorg; Gareth D James; Walter Krauwinkel; Diego Morita; Edgar Will; Jan-Peer Elshoff Journal: Epilepsia Date: 2022-02-23 Impact factor: 6.740