Dataset Information

Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study.

ABSTRACT: To 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.In 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.Across 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.The 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.

SUBMITTER: Chung SS

PROVIDER: S-EPMC4143954 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study.

Chung Steve S SS Fakhoury Toufic A TA Hogan R Edward RE Nagaraddi Venkatesh N VN Blatt Ilan I Lawson Balduin B Arnold Stephan S Anders Bob B Clark Annie M AM Laine Dawn D Meadows R Shawn RS Halvorsen Mark B MB

Epilepsia 20140605 7

<h4>Objective</h4>To 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.<h4>Methods</h4>In 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 ...[more]

PMID: 24902983

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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.

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.

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.

Dataset Information

Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study.

Publications

Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study.

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