The online version of this article (doi:10.1186/s12888-017-1291-5) contains supplementary material, which is available to authorized users.
The management of acute agitation manifesting in patients with schizophrenia or bipolar disorder requires swift pharmacological intervention to provide rapid symptomatic relief and prevent escalation to aggression and violence. Antipsychotic medications are widely used in this setting and the availability of an inhaled formulation with deep lung absorption of the antipsychotic loxapine has the potential to deliver a faster onset of therapeutic effect than the available intramuscular formulations of antipsychotics.
The efficacy of inhaled loxapine and the alternative antipsychotic aripiprazole delivered via intramuscular (IM) injection will be compared in the Phase IIIb PLACID study. Adults (18–65 years) with a confirmed diagnosis of schizophrenia or bipolar I disorder presenting with acute agitation will be randomly assigned to open-label treatment in a 1:1 ratio. Clinical evaluation will be conducted by raters blinded to treatment assignment. The primary efficacy endpoint is time to response (defined as a Clinical Global Impression of Improvement [CGI-I] score of 1 [very much improved] or 2 [much improved]).
Secondary endpoints will include the percentage of responders at different time points after dosing; the proportion of patients who receive 1 or 2 doses of study drug; time to second dose; time to rescue medication; satisfaction with study drug (evaluated using Item 14 of the Treatment Satisfaction Questionnaire for Medication); and safety and tolerability. Approximately 360 patients will be recruited with an interim analysis conducted once 180 patients have completed the study to decide whether to stop for futility or continue with or without an increase in the sample size up to additional 288 patients.
The PLACID trial will assess the efficacy and safety of inhaled loxapine with deep lung absorption compared with the IM antipsychotic, aripiprazole, in acutely agitated patients with schizophrenia or bipolar disorder. In the event that the median time to response of inhaled loxapine is significantly shorter than that of the intramuscular aripiprazole, the PLACID study has the potential to support the inhaled antipsychotic therapy as the standard of care in this setting.
The study protocol was registered with the European Clinical Trials Database on the 31 October 2014 (EudraCT number 2014–000456-29).
World Health Organization. Trastornos mentales. Available at: http://www.who.int/mediacentre/factsheets/fs396/es/.
Jimenez X, Espila JL, Gallant J. Activation codes: past, present and future in Spain. Emergencies. 2011;23:311–8.
Garrido Viñado E, Lizano-Díez I, Roset Arissó PN, et al. El coste económico de los procedimientos de contención mecánica de origen psiquiátrico en España. Psiquiatr Biológica. 2015;22:12–6. CrossRef
Rubio-Valera M, Luciano JV, Ortiz JM, Slavador-Carulla L, Gracia A, Serrano-Blanco A. Health service use and costs associated with aggressiveness or agitation and containment in adult psychiatric care: a systematic review of the evidence. BMC Psychiatry. 2015;15:417.
Abilify® 7.5 mg/mL solution for injection. Summary of Product Characteristics. Otsuka Pharmaceutical Europe Ltd. 4 June 2009. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000471/WC500020170.pdf.
Popovic D, Nuss P, Vieta E. Revisiting loxapine: a systematic review. Ann General Psychiatry. 2015;14:15. CrossRef
Adasuve® 9.1 mg inhalation powder. Summary of Product Characteristics. Alexza UK Ltd. 20 February 2013.
Guy W. Clinical global impressions (CGI) ECDEU assessment Manual for psychopharmacology, US Department of Health Education, and welfare publication (ADM); 1976. p. 76–338.
Atkinson MJ, Sinha A, Hass SL, Colman SS, Kumar RN, Brod M, et al. Validation of a general measure of treatment satisfaction, the treatment satisfaction Questionnaire for medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2:12. CrossRefPubMedPubMedCentral
Busner J, Steven D, Targum MD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007;4(7):28–37.
Montoya A, Valladares A, Lizan L, et al. Validation of the excited component of the positive and negative syndrome scale (PANSS-EC) in a naturalistic sample of 278 patients with acute psychosis and agitation in a psychiatric emergency room. Health Qual Life Outcomes. 2011;9:18. CrossRefPubMedPubMedCentral
- Rationale and design of the PLACID study: a randomised trial comparing the efficacy and safety of inhaled loxapine versus IM aripiprazole in acutely agitated patients with schizophrenia or bipolar disorder
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