Bapineuzumab for mild to moderate Alzheimer's disease in two global, randomized, phase 3 trials.

BACKGROUND: Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer's disease (AD). METHODS: Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E ε4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale and the Disability Assessment for Dementia. RESULTS: A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event. CONCLUSIONS: These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed. TRIAL REGISTRATION: Noncarriers (3000) ClinicalTrials.gov identifier NCT00667810 ; registered 24 Apr 2008. Carriers (3001) ClinicalTrials.gov identifier NCT00676143 ; registered 2 May 2008.

Phase II crossover trial of varenicline in mild-to-moderate Alzheimer's disease.

BACKGROUND: Evidence supports a role of α4ß2 receptors in Alzheimer's disease (AD). METHODS: This Korean, multicenter, double-blind, two-period (6 weeks each), crossover study randomized participants to the order in which they received varenicline (1 mg twice daily) and placebo. Assessments included AD Assessment Scale-Cognitive Subscale (ADAS-Cog) 75, Neuropsychiatric Inventory (NPI), adverse events (AEs) and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: For varenicline versus placebo (n = 66 randomized), there was no significant difference in the week 6 least square (LS) mean ADAS-Cog 75 total score (primary endpoint; 18.07 vs. 18.49; p = 0.3873) and a slight worsening in the week 6 LS mean NPI (3.82 vs. 2.55; p = 0.0468), primarily driven by decreased appetite/eating. Common treatment-related AEs were nausea (23.3; 3.4%), vomiting (15.0%; 0) and decreased appetite (15.0; 6.8%). CONCLUSIONS: Varenicline did not improve cognition, behavior or global change in this population. The most frequent varenicline-associated AEs were gastrointestinal; psychiatric AEs were rare and similar between the groups.

In-situ cadmium phytoremediation using Solanum nigrum L.: the bio-accumulation characteristics trail.

In this study, Solanum nigrum L. was used in-situ for Cdphytoremediation in Cd polluted soil on Shenyang Zhangshi Irrigation area (SZIA) in 2008. The performance of the plant over the whole growth stage was assessed. Results showed, during the whole experimental stage, the aboveground biomass of single Solanum nigrum L. grew by a factor of 190, from 1.6 +/- 0.4 g to 300.3 +/- 30.2 g with 141.2 times extracted Cd increase from 0.025 +/- 0.001 to 3.53 +/- 0.16 mg. Both the distribution of biomass and amount of extracted Cd in the above-ground part of the plant changed according to the growth of the plant. Particularly, the percentage of biomass and extracted Cd in the stem increased from 20% to 80% and from 11% to 69%, respectively. The bioconcentration factor and transfer factor both varied significantly during the growth of the plant and the lowest values were measured at the flowering stage (0.94 +/- 0.31 and 3.48 +/- 1.14 respectively). The results in this paper provide reference values for the future research on the application of Solanum nigrum L. in phytoremediation and on chemical or/and agricultural strategies for phytoextraction efficiency enhancement.