Phase 2 Results Indicate Evenamide, A Selective Modulator of Glutamate Release, Is Associated With Clinically Important Long-Term Efficacy When Added to an Antipsychotic in Patients With Treatment-Resistant Schizophrenia.

Results from a pilot, 6-week, randomized, open-label, rater-blinded study, with 46-week extension, indicate very good tolerability with exceptional, clinically important, increasing efficacy of evenamide (7.5, 15, and 30 mg bid), a glutamate modulator, as add-on treatment to antipsychotics in 161 treatment-resistant, schizophrenia patients. Ninety-five percent of patients completed 6 weeks (1 discontinued for adverse event), and 89% continued in the extension. Results from the first 100 patients enrolled showed very low attrition over 1 year (77 completers); data pooled from all dose groups showed the Positive and Negative Syndrome Scale total score improved significantly (P < .001; paired t test; last observation carried forward [LOCF]) from baseline at 6 weeks (-9.4), 6 months (-12.7), and 1 year (-14.7); similarly, the proportion of responders (≥20% improvement) increased over time from 6 weeks (16.5%) to 6 months (39%) to 1 year (47.4%). Noteworthy improvement was also observed at each timepoint on the Clinical Global Impression - Severity scale and Clinical Global Impression of Change, indicating progressively increasing efficacy of evenamide up to 1 year.

A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers.

The objectives of this 2-phase study were to elucidate pharmacokinetics (PK), in vivo 24-hour recovery, and red blood cell (RBC) survival properties of RBC-encapsulated dexamethasone sodium phosphate (DSP) prepared using the EryDex System (EDS). The 24-hour RBC recovery and T50 survival phase studied subjects were randomized to receive autologous RBCs loaded with either 15-20 mg DSP (Group 1A) or sham saline (Group 2A). Loaded RBCs were radiolabeled with 51-Cr, and the labeled RBCs were followed over time in vivo. The PK phase evaluated dose levels of 2.5-5 mg (Group 1B) and 15-20 mg (Group 2B) DSP encapsulated in RBCs infused into healthy randomized subjects. The mean ± SD 24-hour RBC recovery was 77.9% ± 3.3% and 72.7% ± 10.5% for Groups 1A and 2A, respectively. The mean ± SD RBC life span was 84.3 ± 8.3 days in Group 1A and 88.9 ± 6.2 days in Group 2A. The PK phase actual DSP loading doses (mean ± SEM) were 4.2 ± 0.27 mg and 16.9 ± 0.90 mg in Groups 1B and 2B, respectively. Release of dexamethasone from RBCs in vivo peaked at 1 hour, and a sustained release of dexamethasone could be detected until 35 days after the single intravenous infusion in Group 2B. The mean RBC in vivo recovery for DSP-loaded processed cells compares similarly to the 24-hour recovery of regulated RBC products intended for transfusion. There was a minimal but acceptable adverse impact on the survival of EDS-processed RBCs. DSP-loaded autologous RBCs, prepared using the EDS, delivered a sustained dose of dexamethasone in vivo.

The efficacy of Tilmanocept in sentinel lymph mode mapping and identification in breast cancer patients: a comparative review and meta-analysis of the 99mTc-labeled nanocolloid human serum albumin standard of care.

Sentinel lymph node (SLN) mapping is common, however question remains as to what the ideal imaging agent is and how such an agent might provide reliable and stable localization of SLNs. (99m)Tc-labeled nanocolloid human serum albumin (Nanocoll) is the most commonly used radio-labeled colloid in Europe and remains the standard of care (SOC). It is used in conjunction with vital blue dyes (VBDs) which relies on simple lymphatic drainage for localization. Although the exact mechanism of Nanocoll SLN localization is unknown, there is general agreement that Nanocoll exhibits the optimal size distribution and radiolabeling properties of the commercially available radiolabel colloids. [(99m)Tc]Tilmanocept is a novel radiopharmaceutical designed to address these deficiencies. Our aim was to compare [(99m)Tc]Tilmanocept to Nanocoll for SLN mapping in breast cancer. Data from the Phase III clinical trials of [(99m)Tc]Tilmanocept's concordance with VBD was compared to a meta-analysis of a review of the literature to identify a (99m)Tc albumin colloid SOC. The primary endpoints were SLN localization rate and degree of localization. Six studies were used for a meta-analysis to identify the colloid-based SOC. Five studies (6,134 patients) were used to calculate the SOC localization rate of 95.91 % (CI 0.9428-0.9754) and three studies (1,380 patients) were used for the SOC SLN degree of localization of 1.6683 (CI 1.5136-1.8230). The lower bound of the confidence interval was used for comparison to Tilmanocept. Tilmanocept data included 148 patients, and pooled analysis revealed a 99.99 % (CI 0.9977-1.0000) localization rate and degree of localization of 2.16 (CI 1.964-2.3600). Tilmanocept was superior to the Nanocoll SOC for both endpoints (P < 0.0001).

Long-term effects of rivastigmine in moderately severe Alzheimer's disease: does early initiation of therapy offer sustained benefits?

Goals of the study included evaluating the long-term efficacy of rivastigmine in Alzheimer's disease (AD) patient categories stratified by baseline dementia severity, and post hoc investigation of particular benefits of early initiation of rivastigmine treatment in moderately severe AD. Both rivastigmine-treated groups (originally randomized to 1-4 or 6-12 mg/day) experienced significantly smaller declines in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores from baseline than the projected placebo group after 52 weeks. Patients receiving rivastigmine from Day 1 experienced significantly less decline compared with patients originally receiving placebo and then initiating rivastigmine treatment after a 6-month delay. Furthermore, cognitive benefits were more robust in patients with moderately severe disease compared with previous reports in mild to moderately severe AD. Findings suggest that early treatment with rivastigmine 6-12 mg/day is associated with sustained long-term cognitive benefits in patients with moderately severe AD. The results support the value of early treatment of AD patients, particularly those with moderately severe AD.