lacosamide and Headache

To evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic generalised epilepsy (IGE).. Phase 3, double-blind, randomised, placebo-controlled trial (SP0982; NCT02408523) in patients with IGE and PGTCS taking 1-3 concomitant antiepileptic drugs. Primary outcome was time to second PGTCS during 24-week treatment.. 242 patients were randomised and received ≥1 dose of trial medication (lacosamide/placebo: n=121/n=121). Patients (mean age: 27.7 years; 58.7% female) had a history of generalised-onset seizures (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). Median treatment duration with lacosamide/placebo was 143/65 days. Risk of developing a second PGTCS during 24-week treatment was significantly lower with lacosamide than placebo (Kaplan-Meier survival estimates 55.27%/33.37%; HR 0.540, 95% CI 0.377 to 0.774; p<0.001; n=118/n=121). Median time to second PGTCS could not be estimated for lacosamide (>50% of patients did not experience a second PGTCS) and was 77.0 days for placebo. Kaplan-Meier estimated freedom from PGTCS at end of the 24-week treatment period (day 166) for lacosamide/placebo was 31.3%/17.2% (difference 14.1%; p=0.011). More patients on lacosamide than placebo had ≥50% (68.1%/46.3%) or ≥75% (57.1%/36.4%) reduction from baseline in PGTCS frequency/28 days, or observed freedom from PGTCS during treatment (27.5%/13.2%) (n=119/n=121). 96/121 (79.3%) patients on lacosamide had treatment-emergent adverse events (placebo 79/121 (65.3%)), most commonly dizziness (23.1%), somnolence (16.5%), headache (14.0%). No patients died during the trial.. Lacosamide was efficacious and generally safe as adjunctive treatment for uncontrolled PGTCS in patients with IGE.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dizziness; Double-Blind Method; Drug Therapy, Combination; Epilepsy, Generalized; Female; Headache; Humans; Kaplan-Meier Estimate; Lacosamide; Male; Middle Aged; Proportional Hazards Models; Seizures; Sleepiness; Treatment Outcome; Young Adult

A large-scale, double-blind trial (SP0993; NCT01243177) demonstrated that lacosamide was noninferior to controlled-release carbamazepine (carbamazepine-CR) in terms of efficacy, and well tolerated as first-line monotherapy in patients (≥16 years of age) with newly diagnosed epilepsy. We report primary safety outcomes from the double-blind extension of the noninferiority trial (SP0994; NCT01465997) and post hoc analyses of pooled long-term safety and efficacy data from both trials.. Patients were randomized 1:1 to lacosamide or carbamazepine-CR. Doses were escalated (lacosamide: 200/400/600 mg/d; carbamazepine-CR: 400/800/1200 mg/d) based on seizure control. Eligible patients continued randomized treatment in the extension. Primary outcomes of the extension were treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Post hoc analyses of data from combined trials included 12- and 24-month seizure freedom and TEAEs by number of comorbid conditions.. A total of 886 patients were treated in the initial trial and 548 in the extension; 211 of 279 patients (75.6%) on lacosamide and 180/269 (66.9%) on carbamazepine-CR completed the extension. In the extension, 181 patients (64.9%) on lacosamide and 182 (67.7%) on carbamazepine-CR reported TEAEs; in both groups, nasopharyngitis, headache, and dizziness were most common. Serious TEAEs were reported by 32 patients (11.5%) on lacosamide and 22 (8.2%) on carbamazepine-CR; 12 (4.3%) and 21 (7.8%) discontinued due to TEAEs. In the combined trials (median exposure: lacosamide 630 days; carbamazepine-CR 589 days), Kaplan-Meier estimated proportions of patients with 12- and 24-month seizure freedom from first dose were 50.8% (95% confidence interval 46.2%-55.4%) and 47.0% (42.2%-51.7%) on lacosamide, and 54.9% (50.3%-59.6%) and 50.9% (46.0%-55.7%) on carbamazepine-CR. Incidences of drug-related TEAEs and discontinuations due to TEAEs increased by number of comorbid conditions and were lower in patients on lacosamide.. Long-term (median ~2 years) lacosamide monotherapy was efficacious and generally well tolerated in adults with newly diagnosed epilepsy. Seizure freedom rates were similar with lacosamide and carbamazepine-CR.

Topics: Adult; Anticonvulsants; Carbamazepine; Delayed-Action Preparations; Dizziness; Double-Blind Method; Epilepsy; Female; Headache; Humans; Lacosamide; Male; Middle Aged; Time Factors; Treatment Outcome; Young Adult

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

This multicenter, double-blind, double-dummy, randomized, inpatient trial evaluated the safety, tolerability, and pharmacokinetics of intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures.. Patients were enrolled from an ongoing open-label extension trial of oral lacosamide and randomized (2:1) to either intravenous lacosamide and oral placebo or intravenous placebo and oral lacosamide. During the 2-day inpatient treatment period, patients received twice-daily doses of lacosamide equivalent to their current daily dose of oral lacosamide. The first 30 patients enrolled received infusions with 60-min durations and the next 30 received infusions with 30-min durations.. Of 60 patients randomized, 59 completed the trial. Treatment-emergent adverse events (AEs) were reported by 16 patients and included dizziness, headache, back pain, somnolence, and injection site pain. The tolerability profile of intravenous lacosamide was consistent with that of oral lacosamide. All AEs were considered mild or moderate in intensity, and no serious AEs or AEs leading to withdrawal were reported.. Intravenous lacosamide, administered as 60- or 30-min twice-daily infusions, showed a similar safety and tolerability profile to oral lacosamide when used as replacement therapy. Results from this trial support further investigation of intravenous lacosamide at shorter infusion durations.

Topics: Acetamides; Administration, Oral; Adult; Anticonvulsants; Back Pain; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Female; Headache; Humans; Infusion Pumps; Infusions, Intravenous; Lacosamide; Male; Middle Aged; Placebos; Time Factors; Treatment Outcome

Peripheral diabetic neuropathy affects between 20% and 45% of patients with diabetes.. To ascertain the effect of lacosamide on pain associated with peripheral diabetic neuropathy.. One hundred nineteen patients with a 1 to 5-year history of pain attributed to diabetic neuropathy and a score of > or =4 on the Likert pain scale entered the multicenter, randomized, double-blind, placebo-controlled trial. Lacosamide (N=60) titrated from 100 to 400 mg/d or maximum tolerated dose and placebo (N=59) were the trial interventions. Primary efficacy criterion was change in pain score on the 11-point Likert pain scale. Secondary assessments included Short-Form McGill Pain and Short-Form-36 Quality of Life Questionnaires, sleep/activity interference, pain intensity, Patient and Clinical Global Impression of Change, and Profile of Mood. Patients receiving at least 1 dose of medication underwent safety evaluation.. Ninety-four patients (lacosamide 46; placebo 48) completed the trial. Lacosamide had significantly (P=0.039) better pain relief versus placebo (primary outcome). Improvements were also seen in secondary outcome measures. Adverse events occurred in 52 lacosamide and 44 placebo patients. Common adverse events, occurring in > or =5% of patients, were headache (lacosamide 18%, placebo 22%), dizziness (lacosamide 15%, placebo 8%), and nausea (lacosamide 12%, placebo 7%). Five lacosamide and 3 placebo patients withdrew for adverse events.. Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues.

Topics: Acetamides; Aged; Analgesics; Diabetic Neuropathies; Double-Blind Method; Drug Eruptions; Electrocardiography; Female; Gastrointestinal Diseases; Headache; Heart; Humans; Lacosamide; Male; Middle Aged; Pain Measurement; Quality of Life; Treatment Outcome

Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy.. This was a prospective, single-center, observational study that involved pediatric patients (disease onset age ≥four years) with newly diagnosed focal epilepsy treated with PER or LCM as primary monotherapy. Outcomes included retention, being responders, and seizure-free rates after 3, 6, and 12 months. Adverse events (AEs) were noticed throughout the follow-up period. Behavioral outcomes were evaluated with Achenbach Child Behavior Checklist (CBCL/4-16) at baseline and after three and six months.. Using randomization, 60 patients receiving PER (31 females, 29 males, median age: 7.79 [5.34, 10.16] years, median dose: 3.0 [2.0, 4.0] mg/day) and 60 patients receiving LCM (25 females, 35 males, median age: 7.72 [5.91, 10.72] years, median dose: 150.0 [100.0, 200.0] mg/day) were enrolled in the study. At the 12-month follow-up, the retention rates in the PER and LCM groups, both were 90.4%, and the responder rates were 65.4% and 71.2%, while seizure-free rates were 57.7% and 67.3%, respectively. There were no significant differences in the retention, responder and seizure-free rates between the two groups (P > 0.05). There were no significant differences in the responder rates between patients with BECTS, abnormal brain magnetic resonance imaging (MRI), or types of seizure in the two groups (P > 0.05). In the PER group, 28.8% (15/52) of patients experienced AEs, of which the most frequently reported were irritability (n = 7; 13.5%), dizziness (n = 5; 9.6%), somnolence (n = 3; 5.8%), ataxia (n = 1; 1.9%), headache (n = 1; 1.9%), and rash (n = 1; 1.9%). In the LCM group, 15.4% (8/52) of the patients had AEs, including headache (n = 4; 7.5%), dizziness (n = 4; 7.5%), nausea (n = 2; 3.8%), somnolence (n = 2; 3.8%), irritability (n = 1; 1.9%), stomach ache (n = 1; 1.9%), and vomiting (n = 1; 1.9%). The incidence of irritability was significantly higher in the PER group than in the LCM group (13.5% vs. 1.9%, P = 0.031), which occurred mainly within eight weeks after drug administration. Patients with irritability were not dangerous to surrounding people by the assessment of parental observation in the life. And the symptoms were relieved spontaneously within a few months. The outcomes of total scores, internalizing scores, and externalizing scores of the CBCL did not show statistically significant differences in the PER and LCM groups between baseline and three and six months. Characteristics of behavior and emotion did not have substantial changes in patients treated with PER and LCM monotherapy.. The present study documented similar good effectiveness and good tolerance of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy and showed no behavioral or emotional impact, as assessed by the CBCL. Though the incidence of irritability with PER monotherapy may be higher than that with LCM monotherapy soon after medication initiation, this side effect appears to resolve spontaneously within a few months. At present, this study was the first research about PER and LCM monotherapy in pediatric patients with newly diagnosed focal epilepsy evaluating efficacy, tolerability, and behavior in China.

Topics: Anticonvulsants; Child; Child, Preschool; Dizziness; Epilepsy, Rolandic; Female; Headache; Humans; Irritable Mood; Lacosamide; Male; Prospective Studies; Retrospective Studies; Sleepiness; Treatment Outcome

Topics: Acetamides; Headache; Humans; Lacosamide; Nerve Block