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Safety, Tolerability and Efficacy of Eslicarbazepine Acetate as Adjunctive Therapy in Patients Aged???65 Years with Focal Seizures.

ABSTRACT: BACKGROUND:The incidence of epilepsy is high within the first few years of life, stabilizes over the second through fifth decades, and then rises again. Treatment of elderly patients with antiepileptic drugs (AEDs) is complicated by increased sensitivity to drug effects, altered pharmacokinetics and an increased risk for drug interactions due to polytherapy. On the other hand, the safety and efficacy data of AEDs attained during clinical development programmes are relatively limited for this age group. OBJECTIVE:The aim of this study was to evaluate the safety, tolerability and efficacy of eslicarbazepine acetate (ESL) as adjunctive therapy in patients aged???65 years with focal-onset seizures (FOS). METHODS:This was an international, multicentre, open-label, non-controlled, single-arm, post-European approval commitment study with flexible doses of ESL between 400 and 1200 mg/day. Seventy-two elderly patients with at least two FOS in the prior 4 weeks, and treated with one or two AEDs, were enrolled. The study consisted of an 8-week baseline, followed by a 26-week treatment period during which the investigator was allowed to up- or down-titrate the ESL dose, and a 4-week follow-up period. Safety and tolerability were assessed as well as mental sedation, cognitive mental state and suicidal ideation. Efficacy was assessed based on patient diaries regarding the absolute and relative changes in seizure frequency, change in intellectual impairment and quality of life. RESULTS:Overall, 47 (65.3%) patients experienced 152 treatment-emergent adverse events (TEAEs). The most frequent were dizziness (12.5%), somnolence (9.7%), fatigue, convulsion and hyponatraemia (8.3% each). All patients that experienced hyponatraemia (6/72) recovered without sequelae. Three patients died during the study (due to cardiac failure, glioblastoma multiforme and ischaemic stroke, all considered unrelated to ESL). Overall, 16 (22.2%) patients discontinued prematurely due to TEAEs. The incidences of clinically significant findings were low for vital signs, ECG, physical and neurological examinations. No TEAEs of hypothyroidism were reported; however, 24 (33.3%) patients presented post-baseline shifts from normal to decreased free T4 levels (not clinically significant). ESL decreased standardized seizure frequency from a mean of 4.8 seizures at baseline to 3.6 seizures at endpoint (p?>?0.05); and mean number of days with seizures significantly decreased from 4.1 (baseline) to 2.8 at endpoint (p?=?0.0408). CONCLUSION:ESL taken once daily (400-1200 mg) as adjunctive therapy in patients aged???65 years was found to be safe, well tolerated and efficacious (EudraCT number: 2009-012587-14).

SUBMITTER: Costa R

PROVIDER: S-EPMC6267536 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Safety, Tolerability and Efficacy of Eslicarbazepine Acetate as Adjunctive Therapy in Patients Aged ≥ 65 Years with Focal Seizures.

Costa Raquel R Steinhoff Bernhard B Gama Helena H Ikedo Fábio F Rocha José-Francisco JF Soares-da-Silva Patrício P

Drugs & aging 20181201 12

<h4>Background</h4>The incidence of epilepsy is high within the first few years of life, stabilizes over the second through fifth decades, and then rises again. Treatment of elderly patients with antiepileptic drugs (AEDs) is complicated by increased sensitivity to drug effects, altered pharmacokinetics and an increased risk for drug interactions due to polytherapy. On the other hand, the safety and efficacy data of AEDs attained during clinical development programmes are relatively limited for ...[more]

PMID: 30387043

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Project description:Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ? 65 years and <65 years.Pooled adverse event data from three placebo-controlled trials of 76-206 weeks' duration in older (? 65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test).A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ? 65 years) with saxagliptin and six (none aged ? 65 years) with placebo. Older patients rarely experienced symptomatic confirmed hypoglycemia (fingerstick glucose ? 50 mg/dL; saxagliptin, n=1; placebo, n=2).Saxagliptin add-on therapy was generally well tolerated in older patients aged ? 65 years with type 2 diabetes mellitus, with a long-term safety profile similar to that of placebo.

Project description:ObjectiveTo investigate whether adjunctive eslicarbazepine acetate (ESL) could lead to exacerbation of seizures in some patients.MethodsPost-hoc analysis of data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and 304) for refractory partial-onset seizures (POS). Following an 8-week baseline period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg once daily (2-week titration, 12-week maintenance, 2-4 week tapering-off periods). Patient seizure diary data and seizure treatment-emergent adverse event (TEAE) reports were pooled for analysis.ResultsThe modified intent-to-treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. Titration period: Compared with placebo (32/21%), significantly smaller proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a ≥25/≥50% increase in standardized seizure frequency (SSF) from baseline; there was no significant difference between placebo and ESL 400 mg. Maintenance period: Compared with placebo (20%), significantly smaller proportions of patients taking ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF ≥25%. When evaluating ≥50% increases in SSF, only ESL 800 mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic-clonic (sGTC) seizures during baseline but had ≥1 sGTC seizure during maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%). Fewer patients had a ≥25% increase in sGTC seizure frequency with ESL (400 mg, 11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures reported as TEAEs was low in all treatment groups; incidences were generally lower with ESL versus placebo. Tapering-off period: Similar proportions of patients taking ESL and placebo had a ≥25/≥50% increase in SSF. Seizure TEAE incidence was numerically higher with ESL versus placebo.SignificanceTreatment with adjunctive ESL does not appear to aggravate POS or sGTC seizures.

Project description:OBJECTIVE:Study 311 (NCT02849626) was a global, multicenter, open-label, single-arm study that assessed safety, tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics of once-daily adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with focal seizures (FS) (with/without focal to bilateral tonic-clonic seizures [FBTCS]) or generalized tonic-clonic seizures (GTCS). METHODS:In the 311 Core Study, a 4-week Pre-treatment Period (Screening/Baseline) preceded a 23-week Treatment Period (11-week Titration; 12-week Maintenance) and 4-week Follow-up. Endpoints included safety/tolerability (primary endpoint), median percent change in seizure frequency per 28 days from Baseline (Treatment Period), and 50% responder and seizure-freedom rates (Maintenance Period). Patients were stratified by age (4 to <7; 7 to <12 years) and concomitant enzyme-inducing anti-seizure drug (EIASD) use. RESULTS:One hundred eighty patients were enrolled (FS, n = 149; FBTCS, n = 54; GTCS, n = 31). The Core Study was completed by 146 patients (81%); the most common primary reason for discontinuation was adverse event (AE) (n = 14 [8%]). Mean (standard deviation) daily perampanel dose was 7.0 (2.6) mg/day and median (interquartile range) duration of exposure was 22.9 (2.0) weeks. The overall incidence of treatment-emergent AEs (TEAEs; 89%) was similar between patients with FS (with/without FBTCS) and GTCS. The most common TEAEs were somnolence (26%) and nasopharyngitis (19%). There were no clinically important changes observed for cognitive function, laboratory, or electrocardiogram (ECG) parameters or vital signs. Median percent reductions in seizure frequency per 28 days from Baseline were as follows: 40% (FS), 59% (FBTCS), and 69% (GTCS). Corresponding 50% responder and seizure-freedom rates were as follows: FS, 47% and 12%; FBTCS, 65% and 19%; and GTCS, 64% and 55%, respectively. Improvements in response/seizure frequency from Baseline were seen regardless of age or concomitant EIASD use. SIGNIFICANCE:Results from the 311 Core Study suggest that daily oral doses of adjunctive perampanel are generally safe, well tolerated, and efficacious in children age 4 to <12 years with FS (with/without FBTCS) or GTCS.

Project description:AimsThis post hoc analysis assessed the efficacy and safety/tolerability of adjunctive perampanel in patients from China (aged ?12 years) with focal seizures (FS), with/without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS).MethodsStudy centers in China were identified using data from five double-blind, randomized, phase III studies of adjunctive perampanel (2-12 mg/day) and their open-label extensions (OLEx). Efficacy assessments included median percent reduction in seizure frequency per 28 days, and 50% and 75% responder and seizure-freedom rates. Safety/tolerability assessments included monitoring of treatment-emergent adverse events (TEAEs).ResultsOverall, 277 patients (placebo, n = 79; perampanel, n = 198) were included in the double-blind safety analysis set. The full analysis set comprised 274 patients (FS, n = 238 [placebo, n = 60; perampanel, n = 178]; FBTCS, n = 120 [placebo, n = 31; perampanel, n = 89]; GTCS, n = 36 [placebo, n = 18; perampanel, n = 18]). Median percent reductions in seizure frequency for placebo vs perampanel were as follows: 16.6% vs 32.4% (FS; P < 0.05) and 39.1% vs 48.2% (FBTCS; not significant [NS]) at 4-12 mg/day, and 37.9% vs 82.6% (GTCS; NS) at 8 mg/day; 50% responder rates were 31.7% vs 37.4% (FS; NS), 48.4% vs 51.9% (FBTCS; NS), and 33.3% vs 61.1% (GTCS; NS), respectively. Seizure-freedom rates were 1.7% vs 9.2%, 16.1% vs 25.3%, and 16.7% vs 44.4%, respectively (all NS). Overall, 262 patients entered the OLEx (FS, n = 228; GTCS, n = 34). Perampanel was efficacious for up to four years for FS and FBTCS and up to two years for GTCS. Across the double-blind and OLEx studies, TEAEs were reported in 65.7% and 81.3% of perampanel-treated patients, respectively; the most common was dizziness. Efficacy and safety/tolerability outcomes were generally similar between Chinese and non-Chinese patients.ConclusionAdjunctive perampanel (up to 12 mg/day) may be a suitable treatment for Chinese patients with FS, with/without FBTCS, or GTCS, with similar efficacy and safety/tolerability compared to non-Chinese patients.

Project description:IntroductionThe aim of this study was to compare healthcare resource utilization (HCRU) before and after initiation of eslicarbazepine acetate (ESL) in the long-term care (LTC) setting (rehabilitation center, mental health center, LTC non-skilled nursing facility/assisted-living facility, home health, assisted living, nursing home, other/unknown).MethodsThis retrospective analysis used IQVIA's New Data Warehouse, which includes deterministically linked LTC, prescription, and professional fee claims data and IQVIA Hospital Charge Data Master database. The study period was 1 April 2013 to 31 December 2019. The index date was the date of ESL initiation in the LTC setting. Inclusion criteria were: (1) ≥ 1 new ESL prescription between 1 April 2014 and 31 December 2018; (2) diagnosis of focal seizure (FS) during the 12 months pre-index date; and (3) no ESL prescription during the 12-month period pre-index. A 12-month pre-post analysis compared epilepsy-specific and all-cause HCRU before and after ESL initiation. Categorical variables were compared with McNemar's tests.ResultsA total of 307 patients (mean age 52.2 years, 57.7% male) with FS were included, of whom 24.8% were in nursing homes. Patients used a mean of 3.1 antiseizure drugs prior to initiation of ESL, and 87.9% of patients initiated ESL as adjunctive treatment. There were significant reductions in proportion of patients with epilepsy specific physician office visits, emergency department (ED) visits, hospitalizations, and all-cause physician office visits and hospitalizations in the post-index period compared to the pre-index period (P < 0.05). Similar results were observed in sensitivity (patients with an epilepsy diagnosis) and subgroup analyses [presence or absence of intellectual developmental disorders or age (≥ 65 and < 65 years)].ConclusionProportion of patients with epilepsy-specific physician office visits, ED visits, hospitalizations, and all-cause physician office visits and hospitalizations were significantly reduced following initiation of ESL in patients with FS in LTC.

Dataset Information

Safety, Tolerability and Efficacy of Eslicarbazepine Acetate as Adjunctive Therapy in Patients Aged???65 Years with Focal Seizures.

Publications

Safety, Tolerability and Efficacy of Eslicarbazepine Acetate as Adjunctive Therapy in Patients Aged ≥ 65 Years with Focal Seizures.

Similar Datasets

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