The Effects of Food on the Pharmacokinetics of a Formulated ACP‐103 Tablet in Healthy Volunteers

Vanover, Kimberly E.; Robbins-Weilert, Doris K.; Wilbraham, Darren; Mant, Timothy; Kammen, Daniël P. van; Davis, Robert E.; Weiner, David M.

doi:10.1177/0091270007299361

Cited by 16 publications

(18 citation statements)

References 8 publications

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“…Preliminary studies assessing adverse effects and bioavailability in healthy controls suggested minimal issues with tolerability and long half life of pimavanserin 20-50 mg without interference from food [Vanover et al 2007a[Vanover et al , 2007b. The high affinity of pimavanserin for 5HT2A receptors [Nordstrom et al 2008] stimulated great interest in its potential for treating PDP.…”

Section: Clinical Trials Of Pimavanserin In Pdpmentioning

confidence: 99%

Evidence for the use of pimavanserin in the treatment of Parkinson’s disease psychosis

Sarva

Henchcliffe

2016

Ther Adv Neurol Disord

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder with both motor and nonmotor symptoms (NMS), leading to significant morbidity and caregiver burden. Psychosis is common but is under recognized by physicians. When present, it increases the patient’s risk of hospitalization and nursing home placement and caregiver burden. Although the atypical antipsychotic agent, clozapine, has been considered the gold standard treatment, severe agranulocytosis in 0.38% of patients and more commonly milder leukopenia, resulting in frequent blood testing, limit its use. Pimavanserin, a 5HT2A receptor inverse agonist, has been shown to reduce psychosis in PD without worsening motor symptoms. It is therefore a welcome therapeutic option for this devastating NMS.

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Section: Clinical Trials Of Pimavanserin In Pdpmentioning

confidence: 99%

Evidence for the use of pimavanserin in the treatment of Parkinson’s disease psychosis

Sarva

Henchcliffe

2016

Ther Adv Neurol Disord

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“…To date, two research articles have been published that contain detailed measurements of pharmacokinetic parameters in humans, representing data from two single-center, randomized, double-blind, placebo-controlled, escalating dose studies [42,43] . In the first article, 25 patients were divided into six groups for single-dose treatments: placebo, 20, 50, 100, 200 and 300 mg.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…In the first article, 25 patients were divided into six groups for single-dose treatments: placebo, 20, 50, 100, 200 and 300 mg. The following pharmacokinetic para-meters were then measured: C max , T max , AUC, t ½ , and CL/F [42] . Another group of 24 patients received once-daily doses of placebo, 50, 100 or 150 mg for 2 weeks.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The powdered capsule form of pimavanserin was well tolerated at all doses, and there were no serious treatment-related adverse events (TRAE) at any dose [42,43] . The most common TRAEs reported by patients were drowsiness and postural dizziness, which were reported in about 50% of patients [42,43] .…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…The most common TRAEs reported by patients were drowsiness and postural dizziness, which were reported in about 50% of patients [42,43] .…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

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Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders

Abbas¹,

Roth²

2008

Expert Opinion on Pharmacotherapy

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Background : Pimavanserin tartrate is the first 5-HT 2A inverse agonist to enter clinical trials as a treatment for L -dopa-induced psychosis in Parkinson's disease and for augmentation of low-dose risperidone treatment in schizophrenia. Pimavanserin is also being evaluated as a possible anti-insomnia drug. Objective : To discuss the potential of pimavanserin to fill multiple therapeutic needs. Methods : The problems with currently approved antipsychotics and sleep agents are explored to highlight how pimavanserin might address some longstanding issues in the treatment of psychosis and insomnia. Results/conclusions : In Phase II clinical trials, pimavanserin seemed to be safe, well-tolerated and efficacious in treating L -dopa-induced psychosis without worsening motor symptoms. Pimavanserin also potentiated the therapeutic effects of low-dose risperidone, reduced haloperidol-induced akathisia, and increased slow-wave sleep in older individuals.

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Exposure–response Modeling From the CLARITY Trial of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder

Darwish

Dirks

Passarell

et al. 2023

Clinical Pharm in Drug Dev

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In the 10-week, phase 2 CLARITY study of patients with major depressive disorder, adjunctive therapy to antidepressants with pimavanserin 34 mg once daily statistically significantly improved the Hamilton Depression Rating Scale (HAMD-17) total score (primary endpoint) and Sheehan Disability Scale (SDS) score (secondary endpoint) versus placebo. This analysis characterized the exposure-response (E-R) relationships of pimavanserin in this CLARITY patient population. Exposure measures were estimated for each patient based on population-pharmacokinetic empirical Bayesian estimates. E-R models were developed to describe exposure-efficacy (HAMD-17, SDS, and Clinical Global Impression-Improvement [CGI-I] scale) and exposure-safety relationships (Karolinska Sleepiness Scale [KSS], Massachusetts General Hospital Sexual Functioning Inventory [MGH-SFI], and adverse events [AEs] of headache, sedation, and somnolence) relationships. For the primary efficacy endpoint (HAMD-17 scores), a sigmoid maximum-effect model described the time course of response, and a linear function of pimavanserin exposure was statistically significant. HAMD-17 scores decreased steadily over time following placebo and pimavanserin treatment; separation from placebo increased as peak pimavanserin plasma concentration (C max ) increased. At median pimavanserin C max (34-mg dose), the reduction from baseline in HAMD-17 scores was −11.1 and −13.5 at weeks 5 and 10, respectively. Relative to placebo, the model predicted comparable reductions in HAMD-17 scores at weeks 5 and 10. Similar improvements in favor of pimavanserin were detected with SDS, CGI-I, MGH-SFI, and KSS scores. No E-R relationship was found for AEs. E-R modeling predicted a relationship between higher pimavanserin exposure and improvement in HAMD-17 score and improvement across multiple secondary efficacy endpoints.

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The Effects of Food on the Pharmacokinetics of a Formulated ACP‐103 Tablet in Healthy Volunteers

Cited by 16 publications

References 8 publications

Evidence for the use of pimavanserin in the treatment of Parkinson’s disease psychosis

Evidence for the use of pimavanserin in the treatment of Parkinson’s disease psychosis

Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders

Exposure–response Modeling From the CLARITY Trial of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder

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