Efficacy results of pimavanserin from a multi-center, open-label extension study in Parkinson's disease psychosis patients

This is the final version. Available on open access from Elsevier via the DOI in this recordIntroduction: Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved for hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). We present durability of response with pimavanserin in patients with PDP for an additional 4 weeks of treatment. Methods: This was an open-label extension (OLE) study in patients previously completing one of three double-blind, placebo-controlled (Core) studies. All patients received pimavanserin 34 mg once daily. Efficacy assessments included the Scale for the Assessment of Positive Symptoms (SAPS) PD and H+D scales, Clinical Global Impression (CGI) Improvement and Severity scales and Caregiver Burden Scale (CBS), through 4 weeks in the OLE. Safety assessments were conducted at each visit. Results: Of 459 patients, 424 (92.4%) had a Week 4 efficacy assessment. At Week 4 (10 weeks total treatment), SAPS-PD mean (standard deviation) change from OLE baseline was -1.8 (5.5) and for SAPS-H+D was -2.1 (6.2) with pimavanserin 34 mg. Patients receiving placebo during the Core studies had greater improvements (SAPS-PD -2.9 [5.6]; SAPS-H+D -3.5 [6.3]) during the OLE. For participants treated with pimavanserin 8.5 or 17 mg during the Core studies, further improvement was observed during the OLE with pimavanserin 34 mg. The mean change from Core Study baseline for SAPS-PD score was similar among prior pimavanserin 34 mg and prior placebo-treated participants (-7.1 vs. -7.0). The CGI-I response rate (score of 1 or 2) at Week 4 was 51.4%. Adverse events were reported by 215 (46.8%) patients during the first 4 weeks of OLE. The most common AEs were fall (5.9%), hallucination (3.7%), urinary tract infection (2.8%), insomnia (2.4%), and peripheral edema (2.2%) 4 Conclusions: Patients previously on pimavanserin 34 mg during three blinded core studies had durability of efficacy during the subsequent 4 week OLE SAPS-PD assessment. Patients previously on blinded placebo improved after 4 weeks of OL pimavanserin treatment. These results in over 400 patients from 14 countries support the efficacy of pimavanserin for treating PDP.ACADIA Pharmaceuticals Inc. (San Diego, CA

Use of the cellular model of body composition to describe changes in body water compartments after total fasting, very low calorie diet and low calorie diet in obese men

Introduction: the cellular model of body composition divides the body in body cell mass (BCM), extracellular solids and extracellular fluids. This model has been infrequently applied for the evaluation of weight loss (WL) programmes.Objectives: (1) to assess changes in body compartments in obese men undergoing fasting, very low calorie diet (VLCD) and low calorie diet (LCD); (2) to evaluate two cellular models for the determination of changes in BCM, fat mass (FM) and body fluids.Materials and methods: three groups of six, obese men participated in a total fast (F) for 6 days, a VLCD (2.5?MJ per day) for 3 weeks or an LCD (5.2?MJ per day) for 6 weeks. Body composition was measured at baseline and after small (~5%) and moderate (~10%) WL. FM was measured using a four-compartment model. Total body water (TBW) and extracellular water (ECW) were, respectively, measured by deuterium and sodium bromide dilution and intracellular water (ICW) calculated by difference. Two cellular models were used to measure BCM, FM and body fluids distribution.Results: after about 5%WL changes in TBW were F=?3.2±1.2?kg (P<0.01), VLCD=?1.2±0.6?kg (P<0.01), LCD=?0.3±0.9?kg(n.s.). The contribution of TBW to total body mass loss was indirectly associated with FM loss. ECW increased during fasting (+1.5±3.1?kg, n.s.), decreased during the VLCD (?2.0±1.5?kg, P<0.05) and remained unchanged at the end of the LCD (?0.3±1.6?kg, n.s.). ICW significantly decreased during fasting (?4.7±3.9?kg, P<0.05) but did not change in the LCD and VLCD groups. The loss of BCM was more significant in the fasting group and it was directly associated with changes in ICW.Conclusions: after a 6-day period of fasting we observed more ICW losses and less fat mobilization compared with VLCD and LCD. The cellular model of body composition is suitable for the characterization of changes in body fluids distribution during WL