ESL (800 and 1200mg QD) was effective and well tolerated as adjunctive therapy for adults with refractory POS.

Overall ESL did not produce statistically significant effects on neurocognitive and behavioral functioning in patients with epilepsy aged 6 to 16years. Additionally, ESL was effective in reducing seizure frequency and was well-tolerated.

Purpose We aimed to review systematically the published evidence regarding the effect of questionnaire design on the recall of pharmacological treatments. Methods The electronic databases Pubmed 1 , EMBASE TM , and Cochrane 1 Library were searched from inception to October 2007, using the following search terms: drug utilization, pharmaceutical preparations, pharmacoepidemiology, validation studies, methods, epidemiologic methods, interviews, data collection, and questionnaires. Drug utilization studies comparing different types of questionnaire or methods of questionnaire administration were included. Backward and forward citation tracking were also conducted. Results Eight studies were included in the systematic review, comparing questions asking for specific drugs or indications with open-ended questions (n ¼ 5), evaluating the use of memory aids (n ¼ 1), or studying the influence of response order on recall (n ¼ 2). The studies were heterogeneous, namely regarding the populations evaluated (e.g., pregnant women, hypertensive patients, general population), mode of questionnaire administration (e.g., personal or telephone interview, self-administered), recall period (e.g., current use, 1 week, previous episode of a disease), or drugs evaluated (e.g., analgesics, antimalarials, all medicines). Despite the lack of standardization in presentation of results, the prevalence of drug use may vary between 5 and 40% when drug names and indications or pictures are used as memory aids, or as a result of primacy effects in self-administered questionnaires. The yielding of the questionnaires depended on the pharmacological groups evaluated. Conclusions Scientific work regarding methods for drug utilization data collection is scarce. The available evidence highlights the importance of knowing the questionnaire characteristics for a proper interpretation of results from drug utilization studies. 176 h. gama ET AL. % * Ademi et al 26 : Evaluation of NSAIDs use among men in the previous week; the frequency measure of drug utilization was followed by a symptom-oriented and then by an open-ended question. ** de Jon vam-den Berg 27 : Evaluation of medicines use during pregnancy; the open-ended question was followed by an indication-oriented question and then by a drug-oriented question on vitamins A, B and D and laxatives.Figure 2. Prevalence of drug utilization with questionnaires with different structures (selected results from 2 studies) 180 h. gama ET AL. ** Neutel et al 31 : Evaluation of use of drugs from several groups; drug-category-oriented question (to the previous 30 days) was followed by an open-ended question (to the past 2 days). *** Mitchell et al 30 : Evaluation of use of drugs from several groups; drug-oriented question was followed by a drugoriented one; questions covered the period before conception and through the end of pregnancy.Figure 3. Enhanced prevalence of drug utilization with sequential questions (selected results from 3 studies)

IntroductionEslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.ObjectiveThe objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance.MethodsWe used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015.ResultsFrom a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at daily doses of 1200 mg. Other adverse drug reactions reported in post-marketing surveillance are seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety profile of eslicarbazepine acetate in renal and hepatic impairment subjects (phase I studies) and in elderly patients (phase III study) did not raise any specific concern.ConclusionAfter 6 years of post-marketing surveillance, eslicarbazepine acetate maintains a similar safety profile to that observed in pivotal clinical studies.

Background: Opicapone is a catechol O-methyltransferase (COMT) inhibitor indicated for use as adjunct to levodopa therapy in patients with Parkinson's disease (PD) and motor fluctuations. Objective: To characterize the safety and tolerability of adjunct opicapone (25 and 50 mg) in a pooled population of levodopatreated PD patients who participated in the opicapone Phase-3 clinical program. Methods: Patient-level data (placebo, opicapone 25 mg and 50 mg) from the BIPARK-1 and BIPARK-2 double-blind and open-label studies were combined. Results: Pooled analyses included 766 patients from the double-blind studies and 848 patients from the open-label studies.In the double-blind studies, 63.3% of opicapone-treated patients reported treatment-emergent adverse events (TEAEs) versus 57.2% in the placebo group. The most common TEAEs reported in the opicapone group compared to placebo were dyskinesia, constipation and insomnia. The incidence of serious TEAEs was similar across opicapone and placebo groups (3.5% versus 4.3%, respectively). Overall, 71.3% patients treated with open-label opicapone reported at least one TEAE; most occurred within the first 2 months of the open-label studies, and then decreased thereafter. Throughout the Phase-3 clinical program, there were no serious AEs suggestive of hepatic toxicity, and the incidence of gastrointestinal disorders such as nausea and diarrhea remained low (<2%). There were no relevant changes in laboratory parameters including liver enzymes, vital signs, physical or neurological examinations, or ECG readings. Conclusions: Long-term use of opicapone once-daily over 1-year at doses of 25 mg or 50 mg was generally safe and well tolerated, supporting its clinical usefulness in the management of PD motor fluctuations.

BackgroundThe 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.ObjectiveThe 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).MethodsThis 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.ResultsOverall, 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).ConclusionESL 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).Electronic supplementary materialThe online version of this article (10.1007/s40266-018-0602-y) contains supplementary material, which is available to authorized users.

SummaryPurposePooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate (ESL) added‐on to stable antiepileptic therapy in adults with focal‐onset seizures.MethodsData from 1703 patients enrolled in four phase III double‐blind, randomized, placebo‐controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once‐daily doses for 12 weeks (maintenance period). Pooled efficacy variable was standardized (/4 weeks) seizure frequency (SSF) analyzed over the maintenance period as reduction in absolute and relative SSF and proportion of responders (≥50% reduction in SSF). Pooled safety was analyzed by means of adverse events and clinical laboratory assessments.Results SSF was significantly reduced with ESL 800 mg (P < 0.0001) and 1200 mg (P < 0.0001) compared to placebo. Median relative reduction in SSF was 33.4% for ESL 800 mg and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1% (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender, geographical region, epilepsy duration, age at time of diagnosis, seizure type, and type of concomitant antiepileptic drugs (AED). Incidence of adverse events (AEs) and AEs leading to discontinuation was dose dependent. Most common AEs (>10% patients) were dizziness, somnolence, and nausea. The incidence of treatment‐emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was lower in patients who began taking ESL 400 mg (followed by 400 mg increments to 800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg.ConclusionsOnce‐daily ESL 800 mg and 1200 mg showed consistent results across all efficacy and safety endpoints, independent of study population characteristics and type of concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg increments to 800 or 1200 mg provides optimal balance of efficacy and tolerability.

PurposeTo evaluate the safety/tolerability and efficacy of eslicarbazepine acetate (ESL) as adjunctive therapy in elderly patients with partial-onset seizures (POS).MethodPhase III, multicentre, open-label, non-controlled study in patients aged ≥65 years with ≥2 POS during an 8-week baseline and treated with 1–2 antiepileptic drugs. Following baseline, patients entered a 26-week maintenance period. ESL was initiated at 400 mg once-daily and adjusted (400–1200 mg/day) based on individual response. Safety/tolerability evaluations included treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiogram and physical/neurological examinations. Efficacy evaluations included change in standardised seizure frequency (SSF; seizure frequency/4 weeks).ResultsOf the 72 patients included, 47 (65.3%) experienced 152 TEAEs; most commonly, dizziness (12.5%), somnolence (9.7%), fatigue (8.3%), convulsion (8.3%) and hyponatraemia (8.3%). Three patients died of cardiac failure, glioblastoma multiforme and ischaemic stroke (relationship unlikely/not related). Overall, 16 (22.2%) patients discontinued due to TEAEs. Incidence of clinically significant findings was low for vital signs, electrocardiogram and physical/neurological examinations. SSF decreased from 2.9 at baseline to 1.2 during the maintenance period (median relative change: –54.1%).ConclusionOnce-daily ESL (400–1200 mg) as adjunctive therapy in elderly subjects with POS did not raise major safety concerns and was efficacious. Supported by Bial.