Efficacy of retigabine in adjunctive treatment of partial onset seizures in adults.
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ABSTRACT:
SUBMITTER: Splinter MY
PROVIDER: S-EPMC3825677 | biostudies-other | 2013 Oct
REPOSITORIES: biostudies-other
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Project description:OBJECTIVE:To evaluate long-term outcomes of adjunctive therapy with SPN-804 (Oxtellar XR® , Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), in adults with refractory partial-onset seizures. METHODS:After completing a 16-week double-blind, placebo-controlled trial of SPN-804 at fixed dosages (1200 or 2400 mg QD), patients entering this open-label extension study were converted in blinded fashion to 1200 mg QD SPN-804 as a target starting dose for long-term treatment. Patients were followed for 1 year, during which SPN-804 dosages could be adjusted up to 2400 mg/day according to clinical response. RESULTS:Of 214 patients, 84% completed 1-year open-label treatment. Median maintenance SPN-804 dosage was 1200 mg; <10% of patients required 2400 mg. Median 28-day seizure frequency reduction from baseline was 59%; seizure frequency was reduced ?50% in 58% of patients; 11% were seizure free ?6 months; and 5% were seizure free ?1 year. SPN-804 was discontinued due to adverse events in 5% (n = 10). Incidences of each of the most common adverse events (dizziness, headache, diplopia, nausea, vomiting, balance disorder, blurred vision) were ?15% during 1-year follow-up and occurred most frequently in patients previously naïve to SPN-804. No new safety signals, no clinically significant changes in health status, and no deaths attributable to SPN-804 were observed. CONCLUSION:SPN-804 administered once daily for 1 year was effective as adjunctive therapy in improving seizure control and maintaining therapeutic response in adults with refractory partial-onset seizures. With dosage flexibility, SPN-804 was well tolerated.
| S-EPMC5042072 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy and safety of USL255, Qudexy(™) XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs.MethodsIn this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥ 50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated.ResultsAcross the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life.SignificanceThe PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.
| S-EPMC4143954 | biostudies-literature
Project description:Background. The relative efficacy and safety of lacosamide as adjunctive therapy compared to other antiepileptic drugs has not been well established. Objective. To determine if lacosamide provides improved efficacy and safety, reduced length of hospital stay and improved quality of life compared with other anti-epileptic therapies for adults with partial-onset seizures. Data Sources. A systematic review of the medical literature using Medline (1946-Week 4, 2012), EMBASE (1980-Week 3, 2012), Cochrane Central Register of Controlled Trials (Issue 1 of 12, January 2012). Additional studies were identified (through to February 7, 2012) by searching bibliographies, the FDA drug approval files, clinical trial registries and major national and international neurology meeting abstracts. No restrictions on publication status or language were applied. Study Selection. Randomized controlled trials of lacosamide in adults with partial-onset seizures were included. Data Extraction. Study selection, extraction and risk of bias assessment were performed independently by two authors. Authors of studies were contacted for missing data. Data Synthesis. All pooled analyses used the random effects model. Results. Three trials (1311 patients) met inclusion criteria. Lacosamide increased the 50% responder rate compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]; I(2) = 0%). Discontinuation due to adverse events was statistically significantly higher in the lacosamide arm (RR3.13 [95% CI 1.94 to 5.06]; I(2) = 0%). Individual adverse events (ataxia, dizziness, fatigue, and nausea) were also significantly higher in the lacosamide group. Limitations. All dosage arms from the included studies were pooled to make a single pair-wise comparison to placebo. Selective reporting of outcomes was found in all of the included RCTs. Conclusions. Lacosamide as adjunctive therapy in patients with partial-onset seizures increases the 50% responder rate but with significantly more adverse events compared to the placebo.
| S-EPMC3740140 | biostudies-literature
Project description:Brivaracetam (Briviact): a novel adjunctive therapy for partial-onset seizures.
| S-EPMC5265234 | biostudies-literature
Project description:Assess cognitive effects of adjunctive perampanel in adolescents.In this double-blind study (ClinicalTrials.gov identifier: NCT01161524), patients aged 12 to <18 years with partial-onset seizures despite receiving 1-3 antiepileptic drugs were randomized (2:1) to perampanel or placebo. Perampanel was increased weekly in 2-mg increments to 8-12 mg/day (6-week titration; 13-week maintenance). Changes in neuropsychological outcomes were assessed at end of maintenance: Cognitive Drug Research (CDR) System Global Cognition Score (primary end point), five CDR System domain T-scores (secondary end points), letter fluency, category fluency, and Lafayette Grooved Pegboard Test (LGPT).One hundred thirty-three patients were randomized. In the full analysis set, there were no differences of perampanel (n = 79) vs. placebo (n = 44) in CDR System Global Cognition Score (least squares mean change, -0.6 vs. 1.6; p = 0.145), Quality of Working Memory (1.1 vs. 2.0; p = 0.579), or Power of Attention (-6.9 vs. -2.7; p = 0.219). There were small differences with perampanel vs. placebo in other CDR System domains: improvements in Quality of Episodic Memory (3.0 vs. -1.2; p = 0.012), and worsening in Continuity of Attention (-3.3 vs. 1.6; p = 0.013) and Speed of Memory (0.3 vs. 7.0; p = 0.032). Letter fluency, category fluency, and LGPT were not significantly different between groups. The most frequent adverse events with perampanel were dizziness (30.6%) and somnolence (15.3%).Perampanel did not differ from placebo in the global cognitive score, two of five subdomains, and four other cognitive measures. Perampanel was worse on two and better on one subdomain.
| S-EPMC4785606 | biostudies-literature
Project description:ObjectiveTo assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures.MethodsThis was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1-3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder rate was the primary endpoint for EU registration.ResultsOf 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was -21.0%, -26.3%, and -34.5% for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4%, 37.6%, and 36.1%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5%) patients discontinued, including 40 (10.3%) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia.ConclusionsThis trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable.Classification of evidenceThis study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures.
| S-EPMC3413761 | biostudies-literature
Project description:Introduction: China has ~6 million patients with active epilepsy every year, around 60% of whom suffer from partial-onset seizures. Perampanel (PER) is a novel anti-epileptic drug for partial-onset seizures. PER has been included in the latest Chinese National Reimbursement Drug List (NRDL) in 2020. However, there is still a lack of evaluation evidence on the value of PER in China. Methods: This study selected a health system perspective. A Markov model was established to simulate the lifelong transition of different response levels and calculate the number of seizures in Chinese patients. Based on the utility value and mortality risk, the life years and quality-adjusted life years (QALYs) of patients using PER vs. lacosamide (LCM) were estimated. Efficacy data were derived from clinical trials and the literature. Cost data (in US dollars) included drug costs and medical service costs. A lifetime horizon was adopted. Health outcomes and costs were discounted at an annual discount rate of 5%. Deterministic sensitivity analysis, probability sensitivity analysis, and scenario analysis were performed. The impact of the inclusion of PER in the NRDL on the medical insurance budget over 3 years (2021-2023) was also estimated. Results: Cost-effectiveness analysis indicates that 8 mg/day of PER increases QALYs by 0.054 and saves costs by $2,390 compared with 400 mg/day of LCM. 4 mg/day of PER increases QALYs by 0.010 and saves costs by $860 compared with 200 mg/day of LCM. Deterministic sensitivity analysis reveals that utility value and the extreme discount rate are the factors with the greatest impact on the incremental cost-effectiveness ratio. Probabilistic sensitivity analysis and scenario analysis show that the results are robust. Budget impact analysis indicates that after inclusion of PER in the NRDL, the incremental budget would be $1.28, $2.83, and $4.56 million from 2021 to 2023, respectively, but covering more eligible epileptic patients in the same time (1,918, 4,287, and 8,983, respectively). Conclusion: PER (8 or 4 mg/day) is of relatively high value as an add-on therapeutic regimen for partial-onset seizures in China because of its dominate advantage of cost-effectiveness over LCM and acceptable budget impact.
| S-EPMC8290415 | biostudies-literature
Project description:Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy.
| S-EPMC3759704 | biostudies-literature
Project description:BackgroundCenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. This drug can enhance the inactivated state of voltage-gated sodium channels, preferentially inhibiting the persistent component of the sodium channel current, and acts as a positive allosteric modulator of GABAA receptors, binding at a non-benzodiazepine site.ObjectiveWe assessed the efficacy and safety of adjunctive cenobamate for the treatment of focal-onset seizures in adult patients with epilepsy using meta-analytical techniques.MethodsWe systematically searched (May, week 4, 2020) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry ( http://www.clinicaltrials.gov ). There were no date limitations or language restrictions. Randomized, placebo-controlled, single or double-blinded, add-on trials of cenobamate in adult patients with uncontrolled focal-onset seizures were identified. Main outcomes included the proportion of patients with ≥ 50 and 100% reduction in seizure frequency during the maintenance treatment period compared with baseline and the incidence of treatment withdrawal and adverse events (AEs). Risk ratio (RR) with 95% confidence interval (CI) was estimated for each outcome.ResultsTwo trials were included, overall enrolling 659 patients (442 for the add-on cenobamate group and 217 for the add-on placebo group). Seizure frequency reduction by at least 50% occurred during the maintenance phase in 50.1% of the patients randomized to cenobamate and 23.5% of the placebo-treated participants (RR 2.18, 95% CI 1.67-2.85; p < 0.001). The pooled estimated RR to achieve seizure freedom for the cenobamate group in comparison with placebo was 3.71 (95% CI 1.93-7.14; p < 0.001). Withdrawal from randomized treatment occurred in 16.7 and 11.1% of participants receiving cenobamate and placebo, respectively (RR 1.34, 95% CI 0.85-2.09; p = 0.205). Treatment was discontinued due to AEs in 12.2 and 4.1% of the patients in the active and control arms (RR 2.27, 95% CI 1.08-4.79; p = 0.031). AEs were reported in 76.9 and 66.8% of the patients during treatment with cenobamate and placebo (RR 1.14, 95% CI 1.02-1.26; p = 0.021). The cenobamate-associated AEs included somnolence, dizziness, fatigue, balance disorder, and diplopia.ConclusionsAdjunctive cenobamate in adult patients with uncontrolled focal-onset seizures is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo.
| S-EPMC7658084 | biostudies-literature
Project description:INTRODUCTION:There is an unmet need for well-tolerated antiepileptic drugs (AEDs) that effectively control focal onset seizures. This study aimed to evaluate the economic value of new AEDs in the treatment of focal onset seizure, with or without secondary generalization, in Finnish adults and adolescents with epilepsy, comparing brivaracetam with perampanel as adjunctive AEDs. METHODS:Economic value was assessed using cost-utility analysis. Periods of AED initiation, titration, response assessment (seizure freedom,???50% reduction, no response), switching in no response or treatment-emergent adverse events (TEAEs), and death were simulated using a discrete-event simulation model. Responses and switching were simulated based on a comprehensive Bayesian network meta-analysis. The primary modeled outcome was the 3%/year discounted incremental cost-effectiveness ratio (ICER). Discounted quality-adjusted life-years (QALYs), payer costs (year 2017 Euro) per patient, and net monetary benefit (NMB) were secondary outcomes. Probabilistic and comprehensive deterministic sensitivity analyses were conducted. RESULTS:Brivaracetam was more efficacious and had fewer TEAEs than perampanel and other AEDs. Modeled average 5-year QALYs and costs were 3.671 and €28,297 for brivaracetam and 3.611 and €27,979 for perampanel, respectively. The resulting ICER for brivaracetam versus perampanel was only €5345/QALY gained in a deterministic base case scenario. Brivaracetam had a positive NMB and high probability of cost-effectiveness of €1190 and 71% or €1944 and 80% with the assumed willingness to pay of €25,358 or €38,036/QALY gained, respectively. The primary result was robust, with a positive NMB persistent in all sensitivity analysis scenarios. When switching from brivaracetam to perampanel was excluded from the modeling or switching from perampanel to brivaracetam was included, brivaracetam was cost-saving and more effective than perampanel (dominant). CONCLUSION:These simulated comparisons demonstrated that brivaracetam was more effective and potentially also more affordable than perampanel. Thus, brivaracetam is likely a cost-effective and net beneficial alternative to perampanel for treatment of focal onset seizures. Plain language summary available for this article.
| S-EPMC6979440 | biostudies-literature