lacosamide and Nausea

To evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy.. This historical-controlled, double-blind study (NCT00520741) enrolled patients aged 16-70 years on stable doses of 1-2 antiepileptic drugs (AEDs) and experiencing 2-40 partial-onset seizures per 28 days during the 8-week prospective Baseline. Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose. Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase. The primary assessment was the Kaplan-Meier-predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥ 1 predefined seizure-related exit criterion by day 112, compared with the historical-control threshold (65.3%).. Four hundred twenty-five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥ 1 exit criterion; the Kaplan-Meier-predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6-35.5%) was lower than the historical control. When exit events, withdrawal due to treatment-emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8-37.8%) was also lower than the historical control. Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%). Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to-moderate in intensity. Seventy-two patients (16.9%) discontinued due to TEAEs. Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs.. Lacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy.

Topics: Acetamides; Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Female; Headache; Humans; Lacosamide; Male; Middle Aged; Nausea; Prospective Studies; Treatment Outcome; Young Adult

To evaluate the long-term (up to 5 years exposure) safety and efficacy of lacosamide as adjunctive therapy in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs) in open-label extension trial SP756 (NCT00522275).. Patients who completed the double-blind trial SP754 (NCT00136019) were eligible to participate in this open-label extension trial (SP756). At the conclusion of trial SP754, patients had transitioned to lacosamide 200 mg/day. Subsequent dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure reduction. Treatment-emergent adverse events (TEAEs), vital signs, body weight, clinical laboratory data, electrocardiography studies, and seizure frequency were evaluated.. A total of 308 patients received open-label lacosamide and 138 patients (44.8%) completed the long-term trial. The median modal dose (defined as the daily lacosamide dose a patient received for the longest duration during the treatment period) was 500 mg/day. The percentages of patients with lacosamide exposure >1, >2, >3, or >4 years were 75%, 63%, 54%, and 29%, respectively. Primary reasons for discontinuation were lack of efficacy (26%) and adverse events (11%). Common TEAEs (≥15%) were dizziness, headache, contusion, nausea, convulsion, nasopharyngitis, fall, vomiting, and diplopia. TEAEs that led to discontinuation in ≥1.0% of patients were dizziness (1.6%) and convulsion (1.0%). The median percent reductions from baseline of trial SP754 in 28-day seizure frequency were 53.4%, 55.2%, 58.1%, and 62.5%, respectively, for 1-, 2-, 3-, and 4-year completers. The ≥50% responder rates were 52.8%, 56.5%, 58.7%, and 62.5% for 1-, 2-, 3-, and 4-year completers, respectively. Seven of eight patients on lacosamide monotherapy for ≥12 months were deemed 50% responders. Of patients exposed to lacosamide ≥2 years, 3.1% remained seizure-free for a period ≥2 years.. Long-term (up to 5 years) lacosamide treatment was generally well tolerated. The safety profile of lacosamide observed in this trial is consistent with that established in previous double-blind, placebo-controlled trials. Although the open-label trial design limits the analysis of efficacy, long-term reduction in seizure frequency and maintenance of efficacy was observed.

Topics: Acetamides; Adult; Anticonvulsants; Dizziness; Dose-Response Relationship, Drug; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Lacosamide; Male; Middle Aged; Nausea; Time; Treatment Outcome

This open-label follow-on trial aimed to investigate long-term safety and efficacy of lacosamide in patients with painful diabetic neuropathy.. After 1-week baseline period, lacosamide 100mg/day was started. Each week, based on pain and safety assessments, doses were escalated by 100mg/day to an optimal level, up to a maximum of 400mg/day. Patients then entered the 20-week maintenance period (dose adjusted as needed). Thereafter, patients could opt to continue lacosamide up to about 2.5 years (extension period).. Of the 69 enrolled patients, 47 (68%) completed the 20-week maintenance period and elected to continue into the extension period; 37/69 (54%) patients were in the extension period for more than one year and 34/69 (49%) continued until study termination. The modal lacosamide dose in most patients (54%) was 400mg/day. Headache, upper respiratory tract infection, arthralgia, sinusitis, nasopharyngitis, and back pain were the most frequently reported adverse events (10% of patients). Significant reductions from baseline in Likert pain scores began during dose titration and were sustained throughout the study. Significant improvements were also seen in Neuropathic Pain Scale, Quality of Life scores, and Patient's Global Impression of Change assessment. Of 34 patients at study termination, 32 (90%) elected to continue with lacosamide treatment in another long-term open-label trial (NCT00235443).. The long-term safety profile and sustained efficacy of lacosamide observed in this trial support its continued development for treatment of painful diabetic neuropathy.

Topics: Acetamides; Administration, Oral; Aged; Analgesics; Anticonvulsants; Diabetic Neuropathies; Dizziness; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Lacosamide; Male; Middle Aged; Nausea; Pain Measurement; Patient Satisfaction; Peripheral Nerves; Quality of Life; Stroke; Time; Treatment Outcome

To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions.. During this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis.. Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p=0.0023) and 600 mg/day (p=0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p=0.0038) and 600 mg/day (p=0.0141). Adverse events that appeared dose-related included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs.. In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED.

Topics: Acetamides; Administration, Oral; Anticonvulsants; Ataxia; Dizziness; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Humans; Lacosamide; Nausea; Placebos; Treatment Outcome

Epilepsy causes psychiatric disorders in 20-40% of patients impacting negatively on their quality of life. Lacosamide is a new antiepileptic as adjunctive therapy in partial seizures with or without generalization.. We conducted a study to assess the impact of lacosamide as to the quality of life of epileptic patients. We used the HAD scale for anxiety and depression and QOLIE-10 scale for quality of life. We evaluated the efficacy and tolerability.. We collected prospectively poorly controlled epileptic patients are and added lacosamide treatment. Baseline visit, at 3 and 6 months were performed. The questionnaires are completed and the epilepsy information has been collected.. 31 patients, age 45.5 ± 17.2 years, 64.5% males are included. Number of previous monthly crisis 1.6 ± 1.8. HAD anxiety scale shows a significant improvement at 3 and 6 months. HAD scale for depression reflects a significant improvement in quality parameters. QOLIE-10 shows significant improvement for the group with low quality of life after 3 and 6 months. After 6 months 61.3% of patients have a seizure reduction equal or more than 50% and 54.8% are seizure free. Dizziness is the most common side effect (22.8%). 74.2% continued treatment.. Lacosamide may improve anxiety, depression and quality of life of epileptic patients regardless of seizure control. Response to treatment, adherence and side effects are similar to previous studies.. Efecto de la lacosamida sobre la calidad de vida del paciente con epilepsia.. Introduccion. La epilepsia provoca trastornos psiquiatricos en un 20-40% de los pacientes y repercute de forma negativa en su calidad de vida. La lacosamida es un nuevo antiepileptico que se utiliza como terapia añadida en crisis parciales con o sin generalizacion. Objetivo. Hemos realizado un estudio para valorar el impacto de la lacosamida en cuanto a la calidad de vida del paciente con epilepsia. Se han utilizado la escala hospitalaria de ansiedad y depresion (HADS) y la escala de calidad de vida en la epilepsia (QOLIE-10). Se ha valorado la eficacia y la tolerabilidad. Pacientes y metodos. Se recogen prospectivamente pacientes con epilepsia mal controlada y a los que se añade lacosamida. Se realiza una visita basal, a los tres y a los seis meses. Se cumplimentan los cuestionarios y se recaban los datos sobre la epilepsia. Resultados. Se incluyen 31 pacientes, con una edad media de 45,5 ± 17,2 años, un 64,5% varones. El numero de crisis mensuales previas es de 1,6 ± 1,8. La HADS para ansiedad muestra una mejoria significativa a los tres y seis meses. La HADS para depresion refleja una mejoria significativa en los parametros cualitativos. La QOLIE-10 muestra mejoria significativa para el grupo con baja calidad de vida previa a los tres y seis meses. Tras seis meses, el 61,3% de los pacientes presenta una reduccion de las crisis igual o superior al 50%, y el 54,8% esta libre de crisis. El mareo es el efecto secundario mas frecuente (22,8%). El 74,2% continua con el tratamiento. Conclusiones. La lacosamida podria mejorar la ansiedad, depresion y calidad de vida del paciente epileptico con independencia del control de las crisis. La respuesta al tratamiento, la adhesion y los efectos secundarios son similares a estudios previos.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Anxiety; Depression; Disorders of Excessive Somnolence; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Lacosamide; Male; Middle Aged; Nausea; Prospective Studies; Quality of Life; Severity of Illness Index; Sodium Channel Blockers; Young Adult