Safety and tolerability of lacosamide monotherapy in the elderly: A subgroup analysis from lacosamide trials in diabetic neuropathic pain.

Objective: To assess the safety profile of lacosamide monotherapy in elderly (≥65 years) subjects with diabetic neuropathic pain (DNP). Methods: Of 1,863 DNP subjects in double-blind, randomized, placebo-controlled trials of lacosamide monotherapy (NCT00861445, NCT00235469, NCT00238524, NCT00135109, NCT00350103), 502 were elderly. Safety data from elderly subjects were compared with that of younger subjects (<65 years) within these DNP trials. It should be noted that lacosamide is approved for the treatment of focal (partial-onset) seizures; it is not approved/recommended for the treatment of DNP. Results: Overall, cardiovascular diseases were prevalent in the DNP population, as was the use of cardiac, blood pressure, diabetes, and cholesterol-lowering medications among both young and elderly subjects. The most frequently reported adverse events (AEs) for lacosamide monotherapy (200, 400, and 600 mg/day combined) in elderly versus younger subjects were dizziness (16.2% vs. 13.2%), nausea (10.0% vs. 9.4%), and headache (8.0% vs. 8.7%). Incidences of cardiac disorder AEs were higher in elderly versus younger subjects receiving placebo (6.2% vs. 3.9%), lacosamide 200 (4.8% vs. 3.3%), lacosamide 400 (7.0% vs. 4.1%), and lacosamide 600 mg/day (7.7% vs. 4.0%). Discontinuation rates because of any AE in the elderly versus younger subjects were similar for placebo (8.8% vs. 7.0%) and lacosamide 200 mg/day (9.6% vs. 11.9%) and higher for lacosamide 400 (25.1% vs. 10.8%) and lacosamide 600 mg/day (52.7% vs. 28.3%). Significance: Lacosamide monotherapy was well tolerated in elderly subjects with DNP, with an overall AE profile consistent with that reported in epilepsy trials.

Reinduction with Certolizumab Pegol in Patients with Crohn's Disease Experiencing Disease Exacerbation: 7-Year Data from the PRECiSE 4 Study.

BACKGROUND: Patients with Crohn's disease in whom tumor necrosis factor antagonist therapy fails have limited treatment options, and the benefit of reintroducing the same therapy remains unclear. Here, we report results from PRECiSE 4 (NCT00160706), an open-label extension study of certolizumab pegol in patients who withdrew from the placebo-controlled studies PRECiSE 1 or 2. METHODS: Patients eligible for PRECiSE 4 had Crohn's disease exacerbation on placebo or primary or secondary failure to certolizumab pegol in PRECiSE 1 or 2, and received 400 mg certolizumab pegol subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter up to 360 weeks. We assessed safety (adverse events) and efficacy (clinical remission) of extended certolizumab pegol therapy. RESULTS: Patients enrolled in PRECiSE 4 (N = 310; mean age, 37 yr; 58% female; 95% white) had a mean Crohn's disease duration of 8.5 years before entering the qualifying studies. At weeks 52, 104, and 156, remission rates were 28.5%, 17.5%, and 12.6% by nonremitter imputation, and 63.8%, 60.0%, and 63.5% by observed cases, with 47.4%, 31.9%, and 23.2% of patients, respectively, remaining on therapy. By study end (7.5 yr), 92.3% of patients discontinued therapy, 49% on account of adverse events. No new safety signals emerged. Incidence rate (new cases)/100 patient-years was 6.11 for serious infections and 1.29 for malignancies. CONCLUSIONS: Certolizumab pegol was effective in many patients who previously discontinued certolizumab pegol for lack or loss of response. Thus, discontinuation of therapy may not always be necessary. Safety was consistent with previous findings.

Efficacy and safety of lacosamide in painful diabetic neuropathy.

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.

Efficacy and safety of lacosamide in diabetic neuropathic pain: an 18-week double-blind placebo-controlled trial of fixed-dose regimens.

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.

Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial.

UNLABELLED: The efficacy and tolerability of oral lacosamide (200, 400, and 600 mg/day) was evaluated in patients with painful diabetic neuropathy in a double-blind, randomized, placebo-controlled trial. The primary target dose to be confirmed was lacosamide 400 mg/day. Efficacy was assessed by changes in pain scale scores from baseline, with changes over the last 4 weeks of the 12-week maintenance period regarded as the primary endpoint. Endpoint reductions in mean pain score were higher with all doses of lacosamide, reaching the level of significance with 400 mg/day (P = .05). Over the treatment period (titration + maintenance), pain relief was significantly higher than placebo with lacosamide 400 (P = .02) and 600 mg/day (P = .03). Lacosamide had an early-onset effect with significant reductions over placebo during the titration period. Nonparametric and mixed-model analysis approaches gave similar results, supporting significant efficacy at 400 mg/day. Secondary criteria such as Patient's Global Impression of Change, responder rates, and pain-free days provided additional support. Adverse events included dizziness, nausea, and headache. Incidence of cognitive and behavioral adverse events was low. This trial suggests that lacosamide has beneficial effects and may be a suitable treatment option for patients with diabetic neuropathic pain. PERSPECTIVE: This study presents efficacy and safety results of a phase 3, double-blind, placebo-controlled trial of the anticonvulsant drug lacosamide in patients with painful diabetic neuropathy. Lacosamide treatment at a dose of 400 mg/day reduced diabetic neuropathic pain with a favorable safety and tolerability profile that may be suitable for patients with diabetes.

Ecology of Indian desert : VI. Photoperiods in relation to growth behavior of Solanum surattense burn.

In the present study, the effect of different photoperiods: 3, 6, 9, 12 and 18 hr followed by a dark period in a 24 hr cycle, as well as total darkness, continuous light and diffuse light in relation to growth behaviour was observed in Solanum surattense. The influence on the pattern of root and shoot development, stomata, chlorophyll content, green weight, dry weight, fresh weight, monosaccharides, total nitrogen have been analysed. It appeared that a photoperiod of 12 hr brought about optimum growth in this species.