Efficacy, safety, and tolerability of brivaracetam with concomitant lamotrigine or concomitant topiramate in pooled Phase III randomized, double-blind trials: A post-hoc analysis

• Published in: Epilepsy & behavior Vol. 80; pp. 129 - 134
• Main Authors: Benbadis, Selim, Klein, Pavel, Schiemann, Jimmy, Diaz, Anyzeila, Elmoufti, Sami, Whitesides, John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018
• Subjects: Adjunctive; Adult; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Brivaracetam; Dizziness - chemically induced; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Fatigue - chemically induced; Female; Focal seizure; Humans; Lamotrigine; Lamotrigine - administration & dosage; Lamotrigine - adverse effects; Lamotrigine - therapeutic use; Male; Middle Aged; Pyrrolidinones - administration & dosage; Pyrrolidinones - adverse effects; Pyrrolidinones - therapeutic use; Safety; Seizures - drug therapy; Sleepiness; Topiramate; Topiramate - administration & dosage; Topiramate - adverse effects; Topiramate - therapeutic use; Treatment Outcome; Young Adult; AED; Focal seizure; Topiramate; AE; ILAE; BRV; VGSC; TPM; TEAE; Adjunctive; SV2A; CBZ; Brivaracetam; Safety; LEV; LTG; Lamotrigine
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2017.12.024

The objective was to assess the efficacy and safety of adjunctive brivaracetam (BRV) with concomitant use of lamotrigine (LTG) or topiramate (TPM) in patients with uncontrolled focal seizures. Data were pooled from three randomized, placebo-controlled Phase III studies (NCT00490035/N01252, NCT00464269/N01253, NCT01261325/N01358) of adults with focal (partial-onset) seizures. Patients taking concomitant levetiracetam were excluded from the efficacy populations, but included in the safety populations. This post-hoc analysis reports data from patients taking BRV in the approved therapeutic range (50–200mg/day) concomitantly with LTG or TPM. The number of patients in each of the three BRV dosage groups was small, particularly for the TPM subgroup. Mean percent reduction over placebo in baseline-adjusted focal seizure frequency/28days for BRV 50, 100, and 200mg/day was 8.7, 5.3, and 8.9 in the LTG subgroup (n=220), and 8.4, 21.3, and −4.2 in the TPM subgroup (n=122). The ≥50% responder rate with concomitant LTG or TPM with BRV 50, 100, and 200mg/day or placebo was LTG: 28.1%, 36.1%, 34.1%, and 29.1%; and TPM: 14.3%, 44.4%, 25.0%, and 17.5%. There were numerically ≥50%, ≥75%, ≥90%, and 100% responder rates for patients taking BRV ≥50mg/day compared with placebo in both subgroups. In the LTG and TPM safety populations (n=245 versus n=125), treatment-emergent adverse events (TEAEs) were reported with LTG 68.7% versus 68.4%, and TPM 65.6% versus 57.8% (BRV ≥50mg/day versus placebo). Discontinuations due to TEAEs versus placebo were LTG 7.3% versus 6.3% and TPM 8.2% versus 4.7%. The three most frequently reported TEAEs for both subgroups were somnolence, dizziness, and fatigue. Of these, the incidence of fatigue in the LTG population appeared to increase with dose. In this post-hoc pooled analysis, BRV administered with concomitant LTG or TPM reduced seizure frequency and was generally well tolerated for BRV doses of 50–200mg/day. •This is a post-hoc analysis to assess the efficacy and safety of BRV administered with concomitant LTG or TPM•≥50%, ≥75%, ≥90%, & 100% responder rates in patients on BRV ≥50 mg/day with concomitant LTG or TPM were higher than placebo•No conclusions can be drawn regarding the efficacy of BRV when combined with either LTG or TPM due to low patient numbers•Results support the safety and tolerability of BRV when taken with concomitant LTG or TPM