Showing papers by "ACADIA Pharmaceuticals Inc. published in 2019"

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients With Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY)

Abstract: OBJECTIVE Pimavanserin is a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist. This phase 2 study examined the efficacy and safety of pimavanserin as adjunctive therapy in patients with major depressive disorder (MDD). METHODS This was a multicenter, randomized, double-blind, placebo-controlled study in patients with DSM-5-defined MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Using a 2-stage sequential parallel-comparison design, patients were initially randomized in a 3:1 ratio to placebo or pimavanserin added to ongoing SSRI or SNRI therapy; at 5 weeks, placebo nonresponders were re-randomized to placebo or pimavanserin for an additional 5 weeks. Key endpoints were change from baseline to the end of each stage in 17-item Hamilton Depression Rating Scale (HDRS-17) total score and Sheehan Disability Scale (SDS) score. RESULTS Between December 2016 and October 2018, 207 patients were randomized. For the prespecified pooled Sequential Parallel Comparison Design analyses of Stages 1 and 2, the least squares (LS) mean (SE) difference for the HDRS-17 total score was -1.7 (0.85) (P = .039) and for the SDS score was -0.8 (0.29) (P = .004). At week 5 of Stage 1, LS mean (SE) difference for pimavanserin versus placebo was significant for changes on the HDRS-17 (-4.0 [1.09], P = .0003) and SDS (-1.2 [0.40], P = .0036) with effect sizes of 0.626 and 0.498, respectively. Early and sustained separation of pimavanserin from placebo (P < .05) occurred at 1 week. The most common adverse events with pimavanserin were dry mouth, nausea, and headache. CONCLUSIONS Pimavanserin demonstrated robust efficacy in patients with MDD and an inadequate response to an SSRI or SNRI. Tolerability was consistent with previous experience. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03018340.

Should inverse agonists be defined by pharmacological mechanism or clinical effect

Abstract: Pimavanserin was recently approved for treating hallucinations and delusions associated with Parkinson’s disease.1 It is the first approved drug that selectively targets the 5-HT2A receptor and is termed a selective serotonin inverse agonist. This has motivated a debate about which drugs should be classified as inverse agonists – those that display clear evidence of inverse agonist activity in vitro, or only those that have demonstrated clinical evidence of inverse agonism.2 This is a valid question. Here I advance the view that drugs are defined by their in vitro pharmacological profiles and mechanisms of action to the extent that these mechanisms are understood. Constitutive receptor activity and inverse agonism are now well-defined pharmacological properties, documented at the structural level. Therefore, calling pimavanserin an inverse agonist based on its molecular pharmacology properties is appropriate.

Examining parkinson's disease psychosis treatment outcomes in the real world: interim year 1 findings from the insyte observational study

Abstract: Introduction Parkinson's disease is the second most common neurodegenerative disease, and over half of patients diagnosed will experience the symptoms of psychosis at some point during the course of the disease. Despite the prevalence of Parkinson's disease psychosis (PDP), longitudinal studies have not evaluated treatment modalities and outcomes in actual medical practice, and a considerable gap exists in our understanding of the extent to which outcomes achieved in controlled clinical trials can be replicated in the general population. Healthcare providers managing PDP currently utilize a wide range of antipsychotics (AP) off-label, including those that primarily block postsynaptic dopamine receptors, a practice that goes against specific recommendations from evidence-based reviews. Minimal data are available on AP therapy in PDP, regarding mitigating the burden of PDP by reducing hospitalizations and long-term care facility entry, or in improving other outcomes such as activities of daily living and sleep. Additionally, absent such “real world” data, factors that may be predictive of best clinical, economic, and/or humanistic outcomes cannot be fully ascertained. The goal of the INSYTE Study – Management of Parkinson's Disease Psychosis in Actual Practice – is to examine real-world management of PDP and its treatment outcomes, including the role of medication adjustments and AP usage, as well as the impact of PDP on healthcare resource utilization. The study also evaluates treatment decisions and their effect on humanistic measures, including quality of life, treatment satisfaction, sleep quality, activities of daily living, and patient and caregiver burden. Methods The INSYTE Study is enrolling up to 750 patients and their caregivers, from up to 100 sites in the United States. To achieve the study objectives, a prospective, observational design has been implemented to accommodate and describe standard medical practice associated with PDP management. Patients participating in the INSYTE Study will have a diagnosis of PDP prior to enrollment, or else will meet the symptomatic criteria for the condition (for example, Parkinson's disease with a history of delusions and/or hallucinations). INSYTE employs validated assessment instruments, although as an observational study, it does not impose a predefined visit schedule, medical tests, laboratory tests, procedures, or interventions. The INSYTE Study will compile clinical assessments and other data at follow-up visits for up to three years from enrollment. Results Preliminary baseline findings from 55 enrolling sites indicate that investigators at the majority (75%) of enrolling sites are neurologists, of whom 44% are in private practices, as opposed to academic or hospital-based centers. Baseline findings from 334 enrolled patients indicate that most are Caucasian (95%), male (63%), retired (76%), married (75%), and live in a private residence (92%). Most patients (86%) are participating in INSYTE with a caregiver. Average patient age is 74.7 years. Mean duration since PD and PDP diagnosis were 8.8 and 2.6 years, respectively. At baseline, 12% had no cognitive impairment, 50% had slight or mild impairment, and 38% had moderate or severe impairment. At enrollment, 33% of patients were utilizing an AP: of those, 82% were utilizing AP as monotherapy (primarily pimavanserin [50%] and quetiapine [25%]). Pimavanserin+quetiapine was the most frequently employed combination AP therapy (15%); other combinations ( Conclusions The INSYTE Study is the largest observational study to date to explore PDP treatments and patient outcomes in a real-world (clinical practice) setting. Results from this study will better inform the scientific community on current practices and potentially support updates to treatment guidelines and standards of care for the management of PDP. The findings to date reflect the enrollment of approximately half (n=334) of the planned patients from 55 actively participating sites. These data represent baseline characteristics of the enrolled patients (and caregivers, when present). The currently enrolled patients represent 0–38 years since their PD diagnosis, but an average of 8.8 years, and an average of 2.6 years since PDP symptom onset. Patients were also on a wide array of PDP treatments. To date, patients and caregivers have responded well to various questionnaires, as have healthcare professionals from participating sites. These clinical, economic, and humanistic findings will be updated to reflect year 1 interim analyses in Q1 2019. This research was funded by The INSYTE Observational Study is funded by ACADIA Pharmaceuticals, Inc. (San Diego, CA, USA).

Formulations of pimavanserin

Abstract: Provided herein are capsules containing pimavanserin, processes for manufacturing said capsule, and pharmaceutical compositions containing pimavanserin.