Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study.
Rauck Richard L,Shaibani Aziz,Biton Victor,Simpson Jeff,Koch Brigitte
The Clinical journal of pain
BACKGROUND:Peripheral diabetic neuropathy affects between 20% and 45% of patients with diabetes. OBJECTIVE:To ascertain the effect of lacosamide on pain associated with peripheral diabetic neuropathy. METHODS: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. RESULTS: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. DISCUSSION:Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues.
10.1097/01.ajp.0000210957.39621.b2
Long-term oral lacosamide in painful diabetic neuropathy: a two-year open-label extension trial.
Shaibani Aziz,Biton Victor,Rauck Richard,Koch Brigitte,Simpson Jeffrey
European journal of pain (London, England)
OBJECTIVES:This open-label follow-on trial aimed to investigate long-term safety and efficacy of lacosamide in patients with painful diabetic neuropathy. METHODS: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). RESULTS: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). CONCLUSION:The long-term safety profile and sustained efficacy of lacosamide observed in this trial support its continued development for treatment of painful diabetic neuropathy.
10.1016/j.ejpain.2008.05.016
Efficacy and safety of lacosamide in painful diabetic neuropathy.
Ziegler Dan,Hidvégi Tibor,Gurieva Irina,Bongardt Sabine,Freynhagen Rainer,Sen David,Sommerville Kenneth,
Diabetes care
OBJECTIVE:To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS:Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS:For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS:Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.
10.2337/dc09-1578
Efficacy and safety of lacosamide in diabetic neuropathic pain: an 18-week double-blind placebo-controlled trial of fixed-dose regimens.
Wymer James P,Simpson Jeffrey,Sen David,Bongardt Sabine,
The Clinical journal of pain
OBJECTIVES:The aims of this multicenter, randomized, placebo-controlled, double-blind trial were to confirm the efficacy of lacosamide at a daily dose of 400 mg/d and to explore the efficacy, safety, and tolerability of lacosamide 200 mg/d and 600 mg/d in the treatment of painful diabetic neuropathy. METHODS:The trial consisted of a 2-week run-in period, a 6-week titration phase, and a 12-week maintenance phase, during which patients received placebo or fixed doses of lacosamide 200, 400, or 600 mg/d. No back titration was allowed during the trial. The primary efficacy criterion was the change in Likert pain score from baseline to the average over the last 4 weeks of the maintenance phase in the intent-to-treat population. RESULTS:The lacosamide 400 mg/d group demonstrated statistically significant improvement in Likert pain score over placebo for the primary efficacy measure. At the end of treatment, 58% of patients in the lacosamide 400 mg/d treatment group achieved at least a 2-point or 30% reduction in Likert pain score, compared with 46% of placebo-treated patients. The lacosamide 200 mg/d group separated from placebo, but failed to show statistical significance for any of the primary or secondary outcome measures. The lacosamide 600 mg/d group was significantly more efficacious than placebo in the observed cases but not in the intent-to-treat population. This was probably secondary to a relatively high-premature withdrawal rate due to adverse events that occurred during the titration phase in that group. Overall lacosamide at daily doses of 200 to 400 mg was well tolerated, with 8% of patients discontinuing due to an adverse event from the 200 mg/d group and 23% from the 400 mg/d group compared with 9% in the placebo group. Discontinuations due to adverse events were highest in the 600 mg/d group (40%). The most common adverse events consisted of dizziness, nausea, tremor, headache, and fatigue. Somnolence, cognitive and behavioral side effects, weight change, and edema were notably low. DISCUSSION:Safety and efficacy analyses indicated that lacosamide 400 mg/d provided an optimal balance between efficacy and side effects in patients with painful diabetic neuropathy.
10.1097/AJP.0b013e318196d2b6
[Effectiveness of lacosamide in the treatment of refractory neuropathic pain: an open observational trial].
Gómez-Argüelles José M,Bermejo Pedro E,Lara Manuel,Almajano Jerónimo,Aragón Esther,García del Carrizo Fernando,Blanco M Victoria,Valenzuela-Rojas Francisco J,Colás Juan,Sánchez-Del Valle Octavio,Ceballos M Ángeles,Toribio-Díaz M Elena,Latorre-González Germán,Costa-Frossard Lucienne,Morin-Martin M del Mar
Revista de neurologia
INTRODUCTION:Although different treatments are available for neuropathic pain, these patients are often refractory, which makes it necessary to test treatments that, as they have proven useful in other pathologies, could be effective in neuropathic pain. PATIENTS AND METHODS:The study made use of the medical records of patients who had been treated with lacosamide for neuropathic pain in different hospitals in the central area of the peninsula and who fulfilled similar characteristics in terms of refractoriness to other standard treatments, in a follow-up that lasted at least six months, or who had had to stop treatment with that drug for some reason or another. A sample of 114 patients (61 males and 53 females) with a mean age of 60.5 years was obtained from the data. RESULTS:The most common causes of neuropathic pain were: diabetic polyneuropathy (31.6%), post-herpes neuralgia (22.8%), trigeminal neuralgia (17.5%), suboccipital and lumbar-radicular neuralgia (both 12.3%). Effectiveness was good/very good in most patients, with the mean score on the visual analogue scale after six months dropping from 7.7 to 4.8. No serious side effects were reported in any of the patients, but in 12 and 10 patients no recordings were made beyond six months, due to ineffectiveness and intolerance to the treatment, respectively. CONCLUSIONS:Treatment with lacosamide in neuropathic pain due to different causes could be considered an effective and well-tolerated alternative for patients who fail to respond to standard treatments.
Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial.
Carmland Malin E,Kreutzfeldt Melissa,Holbech Jakob V,Andersen Niels T,Jensen Troels S,Bach Flemming W,Sindrup Søren H,Finnerup Nanna B
Trials
BACKGROUND:Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response. METHODS:This study will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel, phase 2, proof-of-concept, phenotype-stratified study. The study will enroll 108 patients with peripheral neuropathic pain who will be randomized to a 12-week treatment with lacosamide or placebo up to 400 mg/day in a 2:1 ratio. The primary objective is to compare the change in the mean value of the patients' daily ratings of average pain intensity from baseline to the last week of treatment in patients with and without the irritable nociceptor phenotype in the per-protocol population. A supportive objective is to compare the effect of lacosamide with that of placebo in the two phenotypes. Secondary and tertiary outcomes include the Patient Global Impression of Change, pain relief, presence of 30% and 50% pain reduction, sleep disturbance, depression, and anxiety. DISCUSSION:We will examine the concept of individualized therapy based on phenotyping, and expect that this study will provide important information on the usefulness of lacosamide in the treatment of peripheral neuropathic pain. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03777956 . Registered on 18 December 2018.
10.1186/s13063-019-3695-7