| 1. |
|
|
| 2. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
-
Epilepsi
- 2011
-
Ingår i: Läkemedelsboken 2011-2012. - Uppsala. : Läkemedelsverket. - 9789197960502 ; , s. 965-76
-
Bokkapitel (refereegranskat)
|
|
| 3. |
- Ben-Menachem, Elinor, 1945
(författare)
-
Eslicarbazepine acetate: a well-kept secret?
- 2010
-
Ingår i: Epilepsy currents. - : SAGE Publications. - 1535-7511 .- 1535-7597. ; 10:1, s. 7-8
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1–2 antiepileptic drugs (AEDs). METHODS: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n= 102) or once-daily ESL 400 mg (n= 100), 800 mg (n= 98), or 1,200 mg (n= 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). RESULTS: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p= 0.0003) and 800-mg (p= 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56–62% of patients), lamotrigine (25–27%), and valproic acid (22–28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. DISCUSSION: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.
|
|
| 4. |
|
|
| 5. |
- Ben-Menachem, Elinor, 1945
(författare)
-
Introduction
- 2013
-
Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 127, s. 1-2
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ben-Menachem, Elinor, 1945
(författare)
-
Medical management of refractory epilepsy-Practical treatment with novel antiepileptic drugs
- 2014
-
Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 55, s. 3-8
-
Tidskriftsartikel (refereegranskat)abstract
- The ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of differential diagnosis and adherence. Epilepsy surgery as an alternative therapy may be suitable in selected cases. If the diagnosis of epilepsy is established and epilepsy surgery is not appropriate, AED treatment should be optimized. Evidence for how to proceed is lacking. Concepts such as rational polytherapy have been advocated but remain speculative concerning better efficacy based on the use of AEDs with differing modes of action. A variety of new AEDs including rufinamide, lacosamide, vigabatrin, perampanel, and retigabine have been recently introduced in the United States. They are briefly characterized in this update review.
|
|
| 9. |
- Ben-Menachem, Elinor, 1945
(författare)
-
Neurostimulation - Past, Present, and Beyond
- 2012
-
Ingår i: Epilepsy Currents. - : SAGE Publications. - 1535-7597 .- 1535-7511. ; 12:5, s. 188-191
-
Tidskriftsartikel (refereegranskat)abstract
- Neurostimulation as a treatment for epilepsy has been around for almost 20 years in the form of vagus nerve stimulation. Newer types of neurostimulation are being developed and stand on the brink of approval for use. The two newest therapies, not yet approved in the United States, are deep brain stimulation and the Responsive Neurostimulator System . In fact, in Europe, approval has already been given for deep brain stimulation and newer forms of vagus nerve stimulation. Efficacy is similar between these therapies, and side effects are moderate, so what will be the future? The challenge will be to learn how to use these therapies correctly and offer the right treatment for the right patient.
|
|
| 10. |
- Ben-Menachem, Elinor, 1945
(författare)
-
Vaccination and the onset of dravet syndrome.
- 2011
-
Ingår i: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7511. ; 11:4, s. 120-2
-
Tidskriftsartikel (refereegranskat)
|
|
| 11. |
|
|
| 12. |
- Brodie, M. J., et al.
(författare)
-
Zonisamide: its pharmacology, efficacy and safety in clinical trials
- 2012
-
Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 126:SI, s. 19-28
-
Tidskriftsartikel (refereegranskat)abstract
- Zonisamide is a benzisoxazole derivative, chemically unrelated to other antiepileptic drugs, that appears to have multiple mechanisms of action, including inhibition of Na+ channels and reduction of T-type Ca2+ currents. It is currently licensed in Europe and the USA for adjunctive treatment of partial seizures in adults, and in Europe as monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy. Zonisamide displays predictable, dose-dependent pharmacokinetics and has a half-life of similar to 60 h, allowing once- or twice-daily administration. It has a low potential for interactions with other medications, including oral contraceptives. The clinical efficacy of adjunctive zonisamide therapy has been established in four pivotal, phase III, randomized, double-blind, placebo-controlled trials, which together included approximately 850 patients, aged 12-77 years, with refractory partial epilepsy. In all four trials, zonisamide 300-600 mg/day resulted in significant reductions in median total seizure rates vs placebo, and zonisamide was generally well tolerated; the most frequently reported adverse events being somnolence, dizziness and anorexia/weight loss. Subanalysis of the primary European trial indicated that zonisamide was effective when administered as first-line adjunctive treatment, and a long-term extension to the same trial demonstrated that the efficacy and safety/tolerability of adjunctive zonisamide was sustained for up to 36 months. Once-daily monotherapy with zonisamide (200-500 mg/day) has been shown to be non-inferior to, and as well tolerated as, twice-daily monotherapy with controlled-release carbamazepine (400-1200 mg/day) in adults with newly diagnosed partial epilepsy. Zonisamide has also been shown to have favourable long-term retention rates, an important indication of its overall effectiveness.
|
|
| 13. |
- Chung, Steve, et al.
(författare)
-
Examining the clinical utility of lacosamide: pooled analyses of three phase II/III clinical trials.
- 2010
-
Ingår i: CNS drugs. - : Springer Science and Business Media LLC. - 1172-7047. ; 24:12, s. 1041-54
-
Tidskriftsartikel (refereegranskat)abstract
- Lacosamide is an antiepileptic drug (AED) approved for the adjunctive treatment of partial-onset seizures in adults. Completed phase II/III clinical trials of lacosamide provide a valuable opportunity to evaluate clinically relevant aspects of the resulting large patient pool.
|
|
| 14. |
- Glauser, Tracy, et al.
(författare)
-
Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.
- 2013
-
Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 54:3, s. 551-63
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent-to-treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level A efficacy/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy RCTs for patients with generalized seizures/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed RCTs. When selecting a patient's AED, all relevant variables and not just efficacy and effectiveness should be considered.
|
|
| 15. |
- Halford, Jonathan J, et al.
(författare)
-
A randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of adjunctive carisbamate treatment in patients with partial-onset seizures.
- 2011
-
Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 52:4, s. 816-25
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the efficacy, safety, and tolerability of adjunctive carisbamate treatment at 800 mg/day and 1,200 mg/day in patients with partial-onset seizures (POS).
|
|
| 16. |
- Hufnagel, Andreas, et al.
(författare)
-
Long-term safety and efficacy of eslicarbazepine acetate as adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy: Results of a 1-year open-label extension study
- 2013
-
Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 103, s. 262-269
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the long-term safety, tolerability and efficacy of once-daily eslicarbazepine acetate (ESL) as adjunctive therapy in adults with partial-onset seizures. Methods: One-year open-label extension (OLE) study with ESL in patients who completed a randomised, double-blind placebo-controlled trial (study BIA-2093-302; Epilepsy Res. 89 (2010) 278-285). Starting dose was 800. mg once-daily, for 4 weeks; thereafter, dose could be individualised within the 400-1200. mg range. Doses of concomitant antiepileptic drugs were to be kept stable. Results: Overall, 325 patients were enrolled (intent-to-treat population); 223 (68.6%) patients completed 1-year of treatment. ESL median dose was 800. mg once-daily. Compared to the baseline period of the double-blind study completed prior to this OLE study, median seizure frequency decreased by 32% in weeks 1-4, and between 37% and 39% thereafter. The responder rate (seizure reduction ≥50%) was 37% during weeks 1-4 and thereafter ranged between 38% and 42% per 12-week interval. Proportion of seizure-free patients per 12-week interval ranged between 5% and 11%. Improvements from baseline in several Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and Montgomery Asberg Depression Rating Scale (MADRS) scores were observed. Adverse events (AEs) were reported by 83% of patients. AEs occurring in ≥10% of patients were dizziness, headache and somnolence. AEs were usually of mild to moderate intensity. Conclusion: In this study, ESL demonstrated a sustained therapeutic effect and was well tolerated during 1-year add-on treatment of adults with partial-onset seizures. Additionally, significant improvements in quality of life domains and depressive symptoms were observed under long-term treatment with once-daily ESL. © 2012 Elsevier B.V.
|
|
| 17. |
- Kramer, L. D., et al.
(författare)
-
Perampanel for adjunctive treatment of partial- onset seizures: A pooled dose- response analysis of phase III studies
- 2014
-
Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 55:3, s. 423-431
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. MethodsSeizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8mg, and who received an actual (last) dose of 12mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p=0.042), analyses excluded patients from the Latin America region (n=162/1,480; 10.9% of the treated cohort). ResultsOf 372 patients randomized to 8mg in the phase III studies, 273 completed the Maintenance Period at 8mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12mg during the extension blinded Conversion Period (n=217), median percent change in seizure frequency per 28days improved from -32.4% (8mg, phase III Maintenance Period) to -44.2% (12mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8mg and had an actual (last) dose of 12mg during weeks 1-13 of the extension Maintenance Period (n=181), median percent change in seizure frequency per 28days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12mg and continued on that dose during the extension. SignificanceIncreasing perampanel dose from 8 to 12mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.
|
|
| 18. |
- Krauss, Gregory, et al.
(författare)
-
Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures.
- 2010
-
Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 51:6, s. 951-7
-
Tidskriftsartikel (refereegranskat)abstract
- Summary Purpose: Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200-800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures. Methods: This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2-5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations. Results: A total of 160 patients received lacosamide 200-800 mg/day, i.v., for 2-5 days, of which 69% received 400-800 mg/day doses. The most common AEs (reported by /=400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts. Discussion: This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2-5 days) replacement for patients temporarily unable to take oral lacosamide.
|
|
| 19. |
- Krauss, G. L., et al.
(författare)
-
Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: Results from phase III extension study 307
- 2014
-
Ingår i: Epilepsia. - : Blackwell Publishing Inc.. - 0013-9580 .- 1528-1167. ; 55:7, s. 1058-1068
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment. Methods Patients ≥12 years old with partial-onset seizures despite treatment with 1-3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open-label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ECG], laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions. Results Among 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of patients were epilepsy-related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ≥1 year, 5.3% were seizure-free for the entire year. Significance No new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
|
|
| 20. |
- Krauss, G. L., et al.
(författare)
-
Perampanel, a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: Interim results from phase III, extension study 307
- 2013
-
Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 54:1, s. 126-134
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate safety, tolerability, and seizure outcome data during long-term treatment with once-daily adjunctive perampanel (up to 12 mg/day) in patients with refractory partial-onset seizures. Methods: Study 307 was an extension study for patients completing the double-blind phase of three pivotal phase III trials (studies 304, 305, and 306). The study consisted of two phases: an open-label treatment phase (including a 16-week blinded conversion period and a planned 256-week maintenance period) and a 4-week follow-up phase. Patients were blindly titrated during the conversion period to their individual maximum tolerated dose (maximum 12 mg/day). Adverse events (AEs) were monitored throughout the study and seizure frequency recorded. The interim data cutoff date for analyses was December 1, 2010. Key Findings: In total, 1,218 patients were enrolled in the study. At the interim cutoff date, 1,186 patients were in the safety analysis set; 1,089 (91.8%) patients had >16 weeks of exposure to perampanel, 580 (48.9%) patients had >1 year of exposure, and 19 (1.6%) patients had >2 years of exposure. At the interim analysis, 840 (70.8%) patients remained on perampanel treatment. The large majority of patients (n = 1,084 [91%]) were titrated to 10 mg or 12 mg/day. Median (range) duration of exposure was 51.4 (1.1-128.1) weeks. Treatment-emergent AEs were reported in 87.4% of patients. The most frequent were dizziness (43.9%), somnolence (20.2%), headache (16.7%), and fatigue (12.1%). Serious AEs were reported in 13.2% of patients. In the intent-to-treat analysis set (n = 1,207), the frequency of all seizures decreased over the first 26 weeks of perampanel treatment in patients with at least 26 weeks of exposure to perampanel (n = 1,006 [83.3%]); this reduction was maintained in patients with at least 1 year of exposure (n = 588 [48.7%]). The overall median percent changes in seizure frequency in patients included in each 13-week interval of perampanel treatment were -39.2% for weeks 14-26 (n = 1,114), -46.5% for weeks 40-52 (n = 731), and -58.1% for weeks 92-104 (n = 59). Overall responder rates in patients included in each 13-week interval of perampanel treatment were 41.4% for weeks 14-26 (n = 1,114), 46.9% for weeks 40-52 (n = 731), and 62.7% for weeks 92-104 (n = 59). During the blinded conversion period, the reduction in seizure frequency in patients previously randomized to placebo (-42.4%, n = 369) was similar to that in patients previously randomized to perampanel (-41.5%, n = 817). Significance: Consistent with pivotal phase III trials, these interim results demonstrated that perampanel had a favorable tolerability profile in patients with refractory partial-onset seizures over the longer term. The decrease in seizure frequency was consistent and maintained in those patients over at least 1 year of perampanel exposure. © 2012 International League Against Epilepsy.
|
|
| 21. |
- Nyberg, Jenny, 1976, et al.
(författare)
-
Cardiovascular fitness and later risk of epilepsy A Swedish population-based cohort study
- 2013
-
Ingår i: Neurology. - 0028-3878. ; 81:12, s. 1051-1057
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyze the associations between cardiovascular fitness at age 18 years and future risk of epilepsy. Methods: Population-based cohort study of Swedish male conscripts (n = 1,173,079) born in 1950-1987, who were followed for up to 40 years. Data on cardiovascular fitness were collected during conscription exams and linked with hospital registers to calculate later risk of epilepsy using Cox proportional hazard models controlling for several confounders, including familial factors. Results: Epilepsy was recorded in 6,796 individuals during the follow-up time. In fully adjusted models, low and medium cardiovascular fitness (compared with high) at age 18 years was associated with increased risk of future epilepsy (hazard ratio 1.79, 95% confidence interval 1.57-2.03; and hazard ratio 1.36, 95% confidence interval 1.27-1.45, respectively). The associations changed only marginally after adjustment for familial influences and prior severe traumatic brain injury, cerebrovascular disease, or diabetes. Conclusions: Low cardiovascular fitness early in life is associated with an increased risk of epilepsy later in adulthood. These results agree with previous results from animal models. We propose that behaviors that increase cardiovascular fitness may act as positive disease-modifiers for the development of epilepsy.
|
|
| 22. |
- O'Brien, T. J., et al.
(författare)
-
Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development
- 2013
-
Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 54, s. 70-74
-
Tidskriftsartikel (refereegranskat)abstract
- There is a pressing need to address the current major gaps in epilepsy treatment, in particular drug-resistant epilepsy, antiepileptogenic therapies, and comorbidities. A major concern in the development of new therapies is that current preclinical testing is not sufficiently predictive for clinical efficacy. Methodologic limitations of current preclinical paradigms may partly account for this discrepancy. Here we propose and discuss a strategy for implementing a "phase II" multicenter preclinical drug trial model based on clinical phase II/III studies designed to generate more rigorous preclinical data for efficacy. The goal is to improve the evidence resulting from preclinical studies for investigational new drugs that have shown strong promise in initial preclinical "phase I" studies. This should reduce the risk for expensive clinical studies in epilepsy and therefore increase the appeal for funders (industry and government) to invest in their clinical development.
|
|
| 23. |
- Paulson, Linda, 1971, et al.
(författare)
-
Effect of levetiracetam on hippocampal protein expression and cell proliferation in rats.
- 2010
-
Ingår i: Epilepsy research. - : Elsevier BV. - 1872-6844 .- 0920-1211. ; 90:1-2, s. 110-20
-
Tidskriftsartikel (refereegranskat)abstract
- Levetiracetam (LEV) is a broad-spectrum antiepileptic drug (AED) with possibly also antiepileptogenic properties. LEV has a specific binding site in the central nervous system and reduces brain excitability; however, the precise mechanism of action (MOA) of LEV remains unclear. To further unravel the potential MOA pathways of LEV we investigated altered protein expression and cell proliferation in rat hippocampal tissue during LEV administration.
|
|
| 24. |
- Rosenfeld, W., et al.
(författare)
-
Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years
- 2014
-
Ingår i: Epilepsy & Behavior. - : Elsevier BV. - 1525-5050. ; 41, s. 164-170
-
Tidskriftsartikel (refereegranskat)abstract
- Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400 mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in N2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for =50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained.
|
|
| 25. |
- Sabers, A., et al.
(författare)
-
A prospective, randomized, multicentre trial for the treatment of refractory status epilepticus, experiences from evaluating the effect of the novel drug candidate, NS1209
- 2013
-
Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 106:1-2, s. 292-295
-
Tidskriftsartikel (refereegranskat)abstract
- Refractory status epilepticus (RSE) is a life-threatening condition that requires immediate and aggressive treatment. Unfortunately, sometimes standard antiepileptic treatment is insufficient. Furthermore, alternative therapeutic options are limited by low evidence of efficacy. The primary objective of this study was to evaluate the effects of the novel drug candidate, NS1209 versus third-line standard treatment (phenytoin/valproate) for RSE. Having not reached the study end-points, the purpose of this paper is to discuss the challenges that are encountered in conducting a controlled study of RSE. This was a phase II, prospective, multicentre, single-blinded, randomized clinical trial and included patients to two separate protocols for convulsive and non-convulsive RSE (NS1209-006 and NS1209-007). In total, 28 patients were included and 14 patients were exposed to NS1209. At study conclusion, the study was insufficiently powered to detect any statistically significant difference between the two treatment groups. This was especially true for the convulsive RSE protocol. We conclude that high-quality studies in RSE are difficult to conduct owing to a number of ethical and practical problems associated with this critical illness. Challenges for further studies are discussed.
|
|
| 26. |
- Steinhoff, B. J., et al.
(författare)
-
Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase III studies
- 2013
-
Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 54:8, s. 1481-1489
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Three phase III studies (304 [ClinicalTrials.gov identifier: NCT00699972], 305 [NCT00699582], 306 [NCT00700310]) evaluated perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose. Methods Patients with partial seizures despite receiving 1-3 antiepileptic drugs were randomized to once-daily placebo, perampanel 8 or 12 mg (studies 304, 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Studies included a 6-week baseline period and double-blind treatment phase (6-week titration; 13-week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double-blind phase) and percentage of patients achieving ≥50% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data. Key Findings The pooled intent-to-treat analysis set (randomized, treated patients with any seizure data) included 1,478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4 mg, -23.3%; 8 mg, -28.8%; 12 mg, -27.2%; placebo, -12.8%; p < 0.01, each dose vs. placebo), as were 50% responder rates (perampanel 4 mg, 28.5%; 8 mg, 35.3%; 12 mg, 35.0%; placebo, 19.3%; p < 0.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4 mg, -31.2%; 8 mg, -35.6%; 12 mg, -28.6%; placebo, -13.9%). Perampanel was generally well tolerated. The most frequent treatment-emergent adverse events (TEAEs) were dizziness, somnolence, and headache. Most TEAEs were mild/moderate; relatively few patients experienced severe TEAEs (placebo, 5.4%; perampanel, 8.9%) or serious TEAEs (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography (ECG) findings, or vital signs. Significance Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile. © 2013 International League Against Epilepsy.
|
|
| 27. |
- Uvebrant, Paul, 1951, et al.
(författare)
-
Terapival vid nydebuterad epilepsi hos barn, vuxna och äldre
- 2011
-
Ingår i: Information från Läkemedelsverket. - 1101-7104. ; 22:1, s. 25-35
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Val av läkemedel vid nydebuterad epilepsi hos barn, vuxna och äldre baseras på typ av anfall, patientrelaterade faktorer som ålder, samtidig sjukdom och medicinering samt läkemedelsegenskaper som effektivitet, farmakokinetik, interaktioner, säkerhet, tolerabilitet, beredningsformer och kostnad. Evidens för läkemedelseffekt kräver omfattande studier vilka ofta saknas, särskilt för de nyare läkemedlen och i synnerhet för barn.
|
|
| 28. |
- Wilcox, K. S., et al.
(författare)
-
Issues related to development of new antiseizure treatments
- 2013
-
Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 54, s. 24-34
-
Tidskriftsartikel (refereegranskat)abstract
- This report represents a summary of the discussions led by the antiseizure treatment working group of the International League Against Epilepsy (ILAE)/American Epilepsy Society (AES) Working Groups joint meeting in London (London Meeting). Wereview here what is currently known about the pharmacologic characteristics of current models of refractory seizures, both for adult and pediatric epilepsy. In addition, we address how the National Institute of Neurological Disorders and Stroke (NINDS)-funded Anticonvulsant Screening Program (ASP) is evolving to incorporate appropriate animal models in the search for molecules that might be sufficiently novel to warrant further pharmacologic development. Wealso briefly address what we believe is necessary, going forward, to achieve the goal of stopping seizures in all patients, with a call to arms for funding agencies, the pharmaceutical industry, and basic researchers.
|
|
