Multi-Discipline Review

Total Page:16

File Type:pdf, Size:1020Kb

Multi-Discipline Review CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 209500Orig1s000 MULTI-DISCIPLINE REVIEW Summary Review Office Director Cross Discipline Team Leader Review Clinical Review Non-Clinical Review Statistical Review Clinical Pharmacology Review NDA 209500 Multi-disciplinary Review and Evaluation Caplyta (lumateperone) NDA/BLA Multi-Disciplinary Review and Evaluation Application Type NDA Application Number(s) 209500 Priority or Standard Standard Submit Date(s) September 27, 2018 Received Date(s) September 27, 2018 PDUFA Goal Date December 27, 2019 Division/Office Division of Psychiatry / Office of Drug Evaluation-I Review Completion Date December 20, 2019 Established/Proper Name Lumateperone (Proposed) Trade Name Caplyta Pharmacologic Class Atypical Antipsychotic Code name ITI-007 Applicant Intra-Cellular Therapies, Inc. Dosage form 42 mg Capsules Applicant proposed Dosing 42 mg by mouth once daily Regimen Applicant Proposed Schizophrenia/Adults Indication(s)/Population(s) Applicant Proposed 58214004 | Schizophrenia (disorder) SNOMED CT Indication Disease Term for each Proposed Indication Recommendation on Approval Regulatory Action Recommended Schizophrenia/Adults Indication(s)/Population(s) (if applicable) Recommended SNOMED 58214004 | Schizophrenia (disorder) CT Indication Disease Term for each Indication (if applicable) Recommended Dosing 42 mg by mouth once daily Regimen 1 Version date: October 12, 2018 Reference ID: 4537404 NDA 209500 Multi-disciplinary Review and Evaluation Caplyta (lumateperone) Table of Contents Table of Tables ................................................................................................................................ 5 Table of Figures ............................................................................................................................. 10 Reviewers of Multi-Disciplinary Review and Evaluation .............................................................. 12 Glossary ......................................................................................................................................... 16 1 Executive Summary ............................................................................................................... 18 Product Introduction ...................................................................................................... 18 Nomenclature................................................................................................................. 18 Conclusions on the Substantial Evidence of Effectiveness ............................................ 18 Benefit-Risk Assessment ................................................................................................ 20 Patient Experience Data ................................................................................................. 30 2 Therapeutic Context .............................................................................................................. 31 Analysis of Condition ...................................................................................................... 31 Analysis of Current Treatment Options ......................................................................... 32 3 Regulatory Background ......................................................................................................... 33 U.S. Regulatory Actions and Marketing History ............................................................. 33 Summary of Presubmission/Submission Regulatory Activity ........................................ 33 4 Significant Issues from Other Review Disciplines Pertinent to Clinical Conclusions on Efficacy and Safety ................................................................................................................. 36 Office of Scientific Investigations ................................................................................... 36 Product Quality .............................................................................................................. 37 Clinical Microbiology ...................................................................................................... 37 Devices and Companion Diagnostic Issues .................................................................... 37 5 Nonclinical Pharmacology/Toxicology................................................................................... 38 Executive Summary ........................................................................................................ 38 Referenced NDAs, BLAs, DMFs ....................................................................................... 44 Pharmacology ................................................................................................................. 45 ADME/PK ........................................................................................................................ 54 Toxicology ....................................................................................................................... 70 General Toxicology .................................................................................................. 70 Genetic Toxicology ................................................................................................ 101 Carcinogenicity ...................................................................................................... 103 Reproductive and Developmental Toxicology ...................................................... 104 Other Toxicology Studies ...................................................................................... 120 2 Version date: October 12, 2018 Reference ID: 4537404 NDA 209500 Multi-disciplinary Review and Evaluation Caplyta (lumateperone) 6 Clinical Pharmacology .......................................................................................................... 123 Executive Summary ...................................................................................................... 123 Summary of Clinical Pharmacology Assessment .......................................................... 125 6.2.1 Pharmacology and Clinical Pharmacokinetics ....................................................... 125 6.2.2 General Dosing and Therapeutic Individualization ................................................ 126 Comprehensive Clinical Pharmacology Review ........................................................... 128 6.3.1 General Pharmacology and Pharmacokinetic Characteristics .............................. 128 6.3.2 Clinical Pharmacology Questions ........................................................................... 129 7 Sources of Clinical Data and Review Strategy ..................................................................... 142 Table of Clinical Studies ................................................................................................ 142 Review Strategy ............................................................................................................ 145 Description of Efficacy and Safety Assessments .......................................................... 145 8 Statistical and Clinical Evaluation ........................................................................................ 150 Review of Relevant Individual Trials Used to Support Efficacy .................................... 150 Study ITI-007-005 (Study 005; ClinicalTrials.gov Identifier NCT01499563) .......... 150 Study ITI-007-005 Results ..................................................................................... 158 Study ITI-007-301 (Study 301; ClinicalTrials.gov Identifier NCT02282761) .......... 170 Study ITI-007-301 Results ..................................................................................... 178 Study ITI-007-302 (Study 302: ClinicalTrials.gov Identifier NCT02469155) .......... 189 Study ITI-007-302 Results ..................................................................................... 198 Assessment of Efficacy across Trials ..................................................................... 209 Integrated Assessment of Effectiveness ............................................................... 215 Review of Safety ........................................................................................................... 216 Safety Review Approach ....................................................................................... 216 Review of the Safety Database ............................................................................. 216 Adequacy of Applicant’s Clinical Safety Assessments .......................................... 217 Safety Results ........................................................................................................ 218 Analysis of Submission-Specific Safety Issues ....................................................... 237 Clinical Outcome Assessment (COA) Analyses Informing Safety/Tolerability ...... 239 Safety Analyses by Demographic Subgroups ........................................................ 240 Specific Safety Studies/Clinical Trials .................................................................... 240 Additional Safety Explorations .............................................................................. 256 Expectations on Safety in the Postmarket Setting ........................................ 257 Integrated Assessment of Safety ................................................................... 257 Statistical Issues ..........................................................................................................
Recommended publications
  • Cervical Schwannoma: Report of Four Cases
    25-Cervical_3-PRIMARY.qxd 7/10/12 5:22 PM Page 345 CASE REPORT Cervical Schwannoma: Report of Four Cases Rohaizam Jaafar, MD (UKM), Tang Ing Ping, MS ORL-HNS (UM), Doris Evelyn Jong Yah Hui, MS ORL-HNS (UKM), Tan Tee Yong, MS ORL-HNS (UM), Mohammad Zulkarnaen Ahmad Narihan, MPATH (UKM) School of Health Sciences, Health Campus, Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. SUMMARY Physical examination revealed a 3 x 3 cm mass located at Extracranial schwannomas in the head and neck region are right lateral upper third of the cervical region. The mass was rare neoplasms. The tumours often present as asymptomatic, firm, mobile and non-tender. She had a right facial nerve slowly enlarging lateral neck masses and determination of palsy (House-Brackman Grade IV) due to a previous operation the nerve origin is not often made until the time of surgery. for a right acoustic neuroma in 2000 and a right supraorbital Preoperative diagnosis maybe aided by imaging studies such wound for a plexiform schwannoma in 2007. as magnetic resonance imaging or computed tomography, while open biopsy is no longer recommended. The accepted A computed tomography of the neck and thorax was treatment for these tumors is surgical resection with performed and showed a well defined, minimally enhancing preservation of the neural pathway. We report four cases of lesion at the left parapharyngeal space measuring 2.4 x 4.3 x cervical schwannomas that we encountered at our center 10 cm. The left carotid sheath vessel is displaced medially. during four years of period.
    [Show full text]
  • The Uptake and Release of Serotonin and Dopamine Associated with Locust (Locusta Migratoria) Salivary Glands
    The Journal of Experimental Biology 199, 699–709 (1996) 699 Printed in Great Britain © The Company of Biologists Limited 1996 JEB0166 THE UPTAKE AND RELEASE OF SEROTONIN AND DOPAMINE ASSOCIATED WITH LOCUST (LOCUSTA MIGRATORIA) SALIVARY GLANDS DECLAN W. ALI AND IAN ORCHARD Department of Zoology, 25 Harbord Street, University of Toronto, Toronto, Ontario, Canada M5S 1A1 Accepted 24 October 1995 Summary The uptake and release characteristics of dopamine and affinity components. [3H]dopamine uptake is Na+- serotonin in the salivary glands of the locust Locusta independent and can be partially reduced by a challenge migratoria were examined. Cyclic AMP levels were with high-K+ saline and by a challenge with ice-cold saline. determined in salivary glands in which the salivary nerve Uptake inhibitors are capable of blocking the uptake of was stimulated under different experimental paradigms. radiolabelled serotonin and dopamine. There is a Ca2+- Stimulation of the salivary nerve leads to time- and dependent efflux of [3H]serotonin and [3H]dopamine from frequency-dependent elevations of cyclic AMP levels in the previously loaded salivary glands in response to glands. The potent and specific D1 receptor antagonist stimulation of the salivary nerve and to treatment with a SCH-23390 is capable of partially inhibiting the high-K+ saline. electrophysiologically induced elevations of cyclic AMP levels. The salivary glands appear to possess uptake transporters for serotonin and dopamine. [3H]serotonin Key words: salivary glands, insect, dopamine, serotonin, cyclic AMP, uptake is Na+-dependent and is composed of high- and low- uptake, release, locust, Locusta migratoria. Introduction Locust salivary glands are innervated via the salivary nerve, evidence to suggest that dopamine and serotonin alter salivary nerve 7b, which is a branch of nerve 7 that originates from the secretory rates (Baines et al.
    [Show full text]
  • Clinical Experience in Schizophrenia: a Neuromedicine New Option to Address Unmet Needs
    Bhat L, Cantillon M, Ings R. Brilaroxazine (RP5063) Clinical Experience in Schizophrenia: A Neuromedicine New Option to Address Unmet Needs. J Neurol Neuromedicine (2018) 3(5): 39-50 www.jneurology.com www.jneurology.com Journal of Neurology && NeuromedicineNeuromedicine Review Article Open Access Brilaroxazine (RP5063) Clinical Experience in Schizophrenia: A New Option to Address Unmet Needs Laxminarayan Bhat*, Marc Cantillon, and Robert Ings Reviva Pharmaceuticals, Inc., Sunnyvale, CA, USA Article Info ABSTRACT Article Notes Schizophrenia is a condition comprising of both treatment and comorbidity Received: September 18, 2018 factors that both complicate its management and present multiple unmet needs. Accepted: October 22, 2018 Brilaroxazine (RP5063), a dopamine (D)/serotonin (5-HT) modulator, possesses in vitro *Correspondence: a broad pharmacology profile against D2/3/4 and 5-HT1A/2A/2B/6/7 receptors, Dr. Laxminarayan Bhat, 1250 Oakmead Parkway, Suite 210, nicotinic acetylcholine (α4β2) receptors, and the serotonin transporter. In Phase 1 Sunnyvale, CA 94085, USA; Telephone No. +1 (408) 816 1454; and 2 clinical experience in healthy volunteers, patients with schizophrenia and Fax No. +1 (408) 904 6270; ORCID Number: 0000-0003-0503- schizoaffective disorder, brilaroxazine was well tolerated, with the repeated 100 mg 8537; Email: lbhat@revivapharma.com. oral dose as the maximum tolerated dose. Investigators observed no cardiometabolic, cardiovascular, prolactin, or neurologic complications. Adherence in Phase 2 was © 2018 Bhat L. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License good with discontinuation rates generally less than placebo. In a Phase 2 evaluation of patients with acute exacerbations in schizophrenia and schizoaffective disorders, brilaroxazine met its primary endpoint of significance versus placebo for Total Positive and Negative Symptom Scale (PANSS) Score at Day 28 as compared to baseline.
    [Show full text]
  • Case Report Head and Neck Schwannomas: a Surgical Challenge—A Series of 5 Cases
    Hindawi Case Reports in Otolaryngology Volume 2018, Article ID 4074905, 10 pages https://doi.org/10.1155/2018/4074905 Case Report Head and Neck Schwannomas: A Surgical Challenge—A Series of 5 Cases Ishtyaque Ansari,1 Ashfaque Ansari,2 Arjun Antony Graison ,2 Anuradha J. Patil,3 and Hitendra Joshi2 1Department of Neurosurgery, MGM Medical College & Hospital, Aurangabad, India 2Department of ENT, MGM Medical College & Hospital, Aurangabad, India 3Department of Plastic Surgery, MGM Medical College & Hospital, Aurangabad, India Correspondence should be addressed to Arjun Antony Graison; drarjunantony@yahoo.com Received 25 September 2017; Accepted 29 January 2018; Published 4 March 2018 Academic Editor: Abrão Rapoport Copyright © 2018 Ishtyaque Ansari et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Schwannomas, also known as neurilemmomas, are benign peripheral nerve sheath tumors. +ey originate from any nerve covered with schwann cell sheath. Schwannomas constitute 25–45% of tumors of the head and neck. About 4% of head and neck schwannomas present as a sinonasal schwannoma. Brachial plexus schwannoma constitute only about 5% of schwannomas. Cervical vagal schwannomas constitute about 2–5% of neurogenic tumors. Methods. We present a case series of 5 patients of schwannomas, one arising from the maxillary branch of trigeminal nerve in the maxillary sinus, second arising from the brachial plexus, third arising from the cervical vagus, and two arising from cervical spinal nerves. Result. Complete extracapsular excision of the tumors was achieved by microneurosurgical technique with preservation of nerve of origin in all except one.
    [Show full text]
  • Lumateperone Monograph
    Lumateperone (Caplyta®) Classification Atypical antipsychotic Pharmacology The mechanism of action of lumateperone tosylate (Caplyta, ITI-007) in the treatment of schizophrenia is unknown but it’s thought to simultaneously modulate serotonin, dopamine, and glutamate neurotransmission. Specifically, lumateperone acts as a potent 5-HT2A receptor antagonist, a D2 receptor presynaptic partial agonist and postsynaptic antagonist, a D1 receptor-dependent modulator of glutamate, and a serotonin reuptake inhibitor. Indication Treatment of schizophrenia in adults Boxed Warning Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Caplyta is not approved for the treatment of patients with dementia-related psychosis. Pharmacokinetics Pharmacokinetic Parameter Details Absorption Rapidly absorbed. Absolute bioavailability is about 4.4%. Cmax reached approximately 1 (fasting) to 2 h (food) post dosing. Ingestion of high fat meal lowers mean Cmax by 33% and increases mean AUC by 9% Distribution Protein binding = 97.4%. Volume of distribution (IV) = 4.1 L/kg Metabolism Extensively metabolized. T1/2 = 13-21 hours for lumateperone and metabolites Excretion Less than 1% excreted unchanged in urine 1 Texas Health and Human Services ● hhs.texas.gov Dosage/Administration 42 mg by mouth once daily with food. Dose titration is not required. Use in Special Population Pregnancy Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Available data from Caplyta use in pregnant women are insufficient to establish any drug associated risks for birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including Caplyta, during pregnancy.
    [Show full text]
  • 2D6 Substrates 2D6 Inhibitors 2D6 Inducers
    Physician Guidelines: Drugs Metabolized by Cytochrome P450’s 1 2D6 Substrates Acetaminophen Captopril Dextroamphetamine Fluphenazine Methoxyphenamine Paroxetine Tacrine Ajmaline Carteolol Dextromethorphan Fluvoxamine Metoclopramide Perhexiline Tamoxifen Alprenolol Carvedilol Diazinon Galantamine Metoprolol Perphenazine Tamsulosin Amiflamine Cevimeline Dihydrocodeine Guanoxan Mexiletine Phenacetin Thioridazine Amitriptyline Chloropromazine Diltiazem Haloperidol Mianserin Phenformin Timolol Amphetamine Chlorpheniramine Diprafenone Hydrocodone Minaprine Procainamide Tolterodine Amprenavir Chlorpyrifos Dolasetron Ibogaine Mirtazapine Promethazine Tradodone Aprindine Cinnarizine Donepezil Iloperidone Nefazodone Propafenone Tramadol Aripiprazole Citalopram Doxepin Imipramine Nifedipine Propranolol Trimipramine Atomoxetine Clomipramine Encainide Indoramin Nisoldipine Quanoxan Tropisetron Benztropine Clozapine Ethylmorphine Lidocaine Norcodeine Quetiapine Venlafaxine Bisoprolol Codeine Ezlopitant Loratidine Nortriptyline Ranitidine Verapamil Brofaramine Debrisoquine Flecainide Maprotline olanzapine Remoxipride Zotepine Bufuralol Delavirdine Flunarizine Mequitazine Ondansetron Risperidone Zuclopenthixol Bunitrolol Desipramine Fluoxetine Methadone Oxycodone Sertraline Butylamphetamine Dexfenfluramine Fluperlapine Methamphetamine Parathion Sparteine 2D6 Inhibitors Ajmaline Chlorpromazine Diphenhydramine Indinavir Mibefradil Pimozide Terfenadine Amiodarone Cimetidine Doxorubicin Lasoprazole Moclobemide Quinidine Thioridazine Amitriptyline Cisapride
    [Show full text]
  • Atypical Antipsychotics TCO 02.2018
    Therapeutic Class Overview Atypical Antipsychotics INTRODUCTION • Antipsychotic medications have been used for over 50 years to treat schizophrenia and a variety of other psychiatric disorders (Miyamato et al 2005). • Antipsychotic medications generally exert their effect in part by blocking dopamine (D)-2 receptors (Jibson et al 2017). • Antipsychotics are divided into 2 distinct classes based on their affinity for D2 and other neuroreceptors: typical antipsychotics, also called first-generation antipsychotics (FGAs), and atypical antipsychotics, also called second- generation antipsychotics (SGAs) (Miyamato et al 2005). • Atypical antipsychotics do not have a uniform pharmacology or mechanism of action; these differences likely account for the different safety and tolerability profiles of these agents (Clinical Pharmacology 2020, Jibson et al 2017). The atypical antipsychotics differ from the early antipsychotics in that they have affinity for the serotonin 5-HT2 receptor in addition to D2. Clozapine is an antagonist at all dopamine receptors (D1-5), with lower affinity for D1 and D2 receptors and high affinity for D4 receptors. Aripiprazole and brexpiprazole act as partial agonists at the D2 receptor, functioning as an ○ agonist when synaptic dopamine levels are low and as an antagonist when they are high. Cariprazine is a partial agonist at D2 and D3. Pimavanserin does not have dopamine blocking activity and is primarily an inverse agonist at 5-HT2A receptors. The remaining atypical antipsychotics share the similarity of D2 and 5-HT2A
    [Show full text]
  • Autophagy in Trypanosomatids
    Cells 2012, 1, 346-371; doi:10.3390/cells1030346 OPEN ACCESS cells ISSN 2073-4409 www.mdpi.com/journal/cells Review Autophagy in Trypanosomatids Ana Brennand 1,†, Eva Rico 2,†,‡ and Paul A. M. Michels 1,* 1 Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, postal box B1.74.01, B-1200 Brussels, Belgium; E-Mail: ana.paesbarreto@uclouvain.be 2 Department of Biochemistry and Molecular Biology, University Campus, University of Alcalá, Alcalá de Henares, Madrid, 28871, Spain; E-Mail: eva.rico@uah.es † These authors contributed equally to this work. ‡ Present Address: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, King’s Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK. * Author to whom correspondence should be addressed; E-Mail: paul.michels@uclouvain.be; Tel.: +32-2-7647473; Fax: +32-2-7626853. Received: 28 June 2012; in revised form: 14 July 2012 / Accepted: 16 July 2012 / Published: 27 July 2012 Abstract: Autophagy is a ubiquitous eukaryotic process that also occurs in trypanosomatid parasites, protist organisms belonging to the supergroup Excavata, distinct from the supergroup Opistokontha that includes mammals and fungi. Half of the known yeast and mammalian AuTophaGy (ATG) proteins were detected in trypanosomatids, although with low sequence conservation. Trypanosomatids such as Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for serious tropical diseases in humans. The parasites are transmitted by insects and, consequently, have a complicated life cycle during which they undergo dramatic morphological and metabolic transformations to adapt to the different environments.
    [Show full text]
  • Comparing the Effectiveness of Mindfulness-Based Cognitive
    Special Issue INTERNATIONAL JOURNAL OF HUMANITIES AND May 2016 CULTURAL STUDIES ISSN 2356-5926 Comparing the effectiveness of mindfulness-based cognitive therapy and treatment based on acceptance and commitment therapy on reducing anxiety and depression in women with post-traumatic stress disorder caused by the accident Najaf Abad city of Esfahan Esmaeil Mardani Zadeh MA in Clinical Psychology Taraz.2002@yahoo.com Elham Yousefi MA in Clinical Psychology yousefi.el64@gmail.com Atousa Khosravi Farsani MA in Psychology Atousa Khosravi@gmail.com Abstract Aims Secondary trauma is a psychological consequence of direct and prolonged contact with a post-traumatic stress disorder person. The purpose of this study was to Compare the effectiveness of mindfulness-based cognitive therapy (MBCT) and treatment based on acceptance and commitment therapy (ACT) on reducing anxiety and depression in women with post-traumatic stress disorder caused by the accident, with controlling the effect of depression, anxiety and stress. Methods: In this quasi-experimental research with pretest-posttest with control group design, 36 women of post-traumatic stress disorder caused by the accident referred to Modarress Psychiatric Hospital of Esfahan, Iran in 2015 were studied. The people who have attained high score on the secondary trauma test were randomly assigned to two experimental groups and one control group. The research instruments were a demographic questionnaire, questionnaire of secondary post-traumatic stress, and questionnaire of depression, anxiety and stress. The interventions (Mindfulness-based cognitive therapy and acceptance commitment therapy) in the experimental group were 8 weeks and once a week, the control group did not receive any training.
    [Show full text]
  • Chronic Olanzapine Or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol Xue-Min Gao, M.D., Kazuo Sakai, M.D., and Carol A
    Chronic Olanzapine or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol Xue-Min Gao, M.D., Kazuo Sakai, M.D., and Carol A. Tamminga, M.D. Chronic haloperidol treatment typically produces late-onset, haloperidol-like chewing in rats, nor did movement ratings purposeless oral chewing movements in laboratory rats with after their chronic administration differ from placebo; a prevalence of 40 to 60%. Chronic clozapine does not whereas, haloperidol produced a 60% prevalence of produce these movements. Based on the phenomenologic purposeless chewing and a prevalence significantly and pharmacologic similarities between these rat chewing increased from placebo. This low rate of oral dyskinesias in movements and human tardive dyskinesia (TD), the animal rats is consistent with several of the preclinical movements are often used as a model of tardive dyskinesia characteristics of the drugs and correlates with their low (TD). Here we report results of the association of oral acute motor side effects in clinical trials. We propose, chewing movements in rats with chronic administration of although have not yet tested in humans, that these animal two new antipsychotic drugs, olanzapine and sertindole. results will predict low TD liability of these drugs. Because each of these antipsychotic drugs has a very low [Neuropsychopharmacology 19:428–433, 1998] incidence of acute Parkinsonism in human studies, they are © 1998 American College of Neuropsychopharmacology. candidates for showing a low tardive dyskinesia risk. Published by Elsevier Science Inc. Neither new drug produced a significant incidence of KEY WORDS: Dyskinesia; Olanzapine; Sertindole; movements parallel certain features (although not all) Haloperidol; Tardive dyskinesia; Chronic neuroleptic of the human neuroleptic-induced dyskinetic syndrome treatment tardive dyskinesia (TD), they are often used in its study.
    [Show full text]
  • Features of the Application of Art-Therapeutic and Gaming Technology Based on Folk Music in Rehabilitation and Socialization of Children with Health Limitations
    Scientific Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 Aug 15; 8(E):373-381. https://doi.org/10.3889/oamjms.2020.3588 eISSN: 1857-9655 Category: E - Public Health Section: Public Health Education and Training Features of the application of art-therapeutic and gaming technology based on folk music in rehabilitation and socialization of children with health limitations Natalia Ivanovna Anufrieva*, Aleksandr Vlavlenovich Kamenets, Marina Viktorovna Pereverzeva, Marina Gennadievna Kruglova Department of Sociology and Philosophy of Art, Russian State Social University, Wilhelm Pieck Street, 4/1, Moscow 129226, Russia Abstract Edited by: Ksenija Bogoeva-Kostovska AIM: The purpose of the work is to study the specifics and evaluate the effectiveness of the use of art-therapeutic Citation: Anufrieva NI, Kamenets AV, Pereverzeva MV, Kruglova MG. Features of the application of art- and gaming technologies based on musical folklore in the course of rehabilitation of children with health limitations. therapeutic and gaming technology based on folk music in rehabilitation and socialization of children with health MATERIALS AND METHODS: The socialization of such children depends largely on the characteristics of health, limitations. Open Access Maced J Med Sci. 2020 Aug 15; the principles of their training, and the effectiveness of the chosen methods. This justifies the need to analyze the 8(E):373-381. https://doi.org/10.3889/oamjms.2020.3588 *Correspondence: Natalia Ivanovna Anufrieva. practical experience and evaluate the results of efforts of specialists who deal with special children. Department of Sociology and Philosophy of Art, Russian State Social University, Wilhelm Pieck Street, 4/1, Moscow RESULTS: The results of the conducted psychological and pedagogical experiment on the use of art-therapeutic and 129226, Russia.
    [Show full text]
  • Synthesis of Novel 6-Nitroquipazine Analogs for Imaging the Serotonin Transporter by Positron Emission Tomography
    University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 2006 Synthesis of novel 6-nitroquipazine analogs for imaging the serotonin transporter by positron emission tomography David B. Bolstad The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Bolstad, David B., "Synthesis of novel 6-nitroquipazine analogs for imaging the serotonin transporter by positron emission tomography" (2006). Graduate Student Theses, Dissertations, & Professional Papers. 9590. https://scholarworks.umt.edu/etd/9590 This Dissertation is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact scholarworks@mso.umt.edu. Maureen and Mike MANSFIELD LIBRARY The University of Montana Permission is granted by the author to reproduce this material in its entirety, provided that this material is used for scholarly purposes and is properly cited in published works and reports. **Please check "Yes" or "No" and provide signature** Yes, I grant permission No, I do not grant permission Author's Signature: Date: C n { ( j o j 0 ^ Any copying for commercial purposes or financial gain may be undertaken only with the author's explicit consent. 8/98 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
    [Show full text]