Long-acting Injection Research Articles

Examining the Awareness, Acceptability, and Adoption of Conventional and non-conventional Forms of Pre-Exposure Prophylaxis (PrEP) for HIV Prevention Among jail-involved Black Sexual Minority men (BSMM) and Black Transgender Women (BTW) in Two Diverse US Cities.

Black sexual minority men (BSMM) and Black transgender women (BTW) are disproportionately impacted by HIV and incarceration in the United States. In-depth interviews (N=34) and ongoing thematic analysis guided by the Exploration Phase of the Exploration, Preparation, Implementation, Sustainment framework were conducted to uncover key themes focused on the awareness, acceptability, and early adoption of conventional (i.e., daily oral pill) and non-conventional forms of PrEP (i.e., long-acting injectable, e-prescription for pick up post release) among jail-involved BSMM and BTW in Chicago, Illinois and Baton Rouge, Louisiana. The majority of participants were cisgender BSMM (88%) and were enrolled in Chicago (65%). There was greater awareness, availability, and adoption of conventional PrEP and non-conventional PrEP e-prescription for pick up post release among Chicago participants compared with Baton Rouge participants. Participants were largely receptive to all three forms of PrEP and stated a high need for HIV prevention in jails and immediately following release. PrEP stigma emerged as a major barrier to conventional daily PrEP adoption while incarcerated; potential misuse (e.g., pill selling) as a potential barrier to PrEP eprescription; and needle aversion and added clinic time as potential barriers to longacting injectable (LAI)-PrEP. Participants indicated that PrEP e-prescription could help support continuity of care post release and highlighted reduced stigma, convenience, and longer-term HIV protection as benefits for LAI-PrEP. Study findings provided context-specific information to inform the implementation of future PrEP interventions for jail-involved BSMM and BTW in two highly HIV-impacted jurisdictions.

Stabilizer-induced different in vivo behaviors for intramuscularly long-acting celecoxib nanocrystals

Nanocrystals (NCs) have been widely recognized as an available policy for the formulation of long-acting injections for insoluble drugs. Stabilizers are extremely important for the physical stability of NCs because they can reduce the surface free energy of the system. However, whether stabilizers can affect the in vivo performances of long-acting injectable NCs is unclear. In this study, three celecoxib (CXB) NCs formulated with different stabilizers (PVP K17, TPGS, and F68) were successfully developed by the wet milling method. Among the formulations, CXB-NCs/PVP K17 had a lower dissolution rate. More importantly, CXB-NCs/PVP K17 did not show burst release after intramuscular (i.m.) injection to rats, and it had a strong analgesic effect. These results showed that the stabilizers played a key role in the in vivo behaviors of long-acting injectable NCs. This strongly suggested that the burst release could be avoided by alteration of stabilizers of NCs by i.m. injection.

Attitude and influencing factors of patients with schizophrenia toward long-acting injections: A community-based cross-sectional investigation in China.

BackgroundLow prescription rates of antipsychotic long-acting injections (LAIs) may be a major challenge in the prevention and treatment of schizophrenia. However, there are few studies on the usage and attitude toward LAIs among community-based patients with schizophrenia.MethodsA large community-based cross-sectional investigation was conducted among 6,336 patients with schizophrenia from Shanghai, China from March 1 to June 30, 2021. The structured Attitude and Status toward Treatment of Community Patients with Schizophrenia Questionnaire (AST-CSQ) was used to investigate the attitude and influencing factors of community-dwelling patients with schizophrenia toward LAIs.ResultsAmong the 6,336 participants, the average age was 49.28 ± 11.23. The rate of agreement to LAI antipsychotics among participants was 3.16% (n = 200). The family financial resources, care ability, and disease course of the LAIs group were less than those of the non-LAIs group. However, the LAIs group had higher immediate family guardianship, social activity, previous hospitalization, number of hospitalization, outpatient adherence, previous antipsychotic use, antipsychotic adherence, and attitude toward oral antipsychotics than the non-LAIs group, with significant differences between the two groups (p < 0.05). Furthermore, age (β = −0.036, OR 0.964, 95% CI 0.947–0.982), marital status (β = 0.237, OR 1.267, 95% CI 1.002–1.602), care ability (β = 0.709, OR 2.032, 95% CI 1.437–2.875), outpatient adherence (β = −0.674, OR 0.510, 95% CI 0.358–0.725), antipsychotic adherence (β = 0.920, OR 2.509, 95% CI 1.092–5.764), and attitude toward oral antipsychotics (β = −1.357, OR 0.258, 95% CI 0.103–0.646) were significant predictors of attitude toward LAI antipsychotics (p < 0.05).ConclusionsThe community-dwelling patients with schizophrenia in China had a low willingness to use LAIs. Patients of a younger age, more hospitalizations, and a shorter course of disease were prone to be more willing to accept LAIs. The patients' age, marital status, care ability, outpatient adherence, antipsychotic adherence, and attitude toward oral antipsychotics were important predictor of patients' attitudes toward LAIs. Under the global deinstitutionalized management model of mental disorders, these results highlight an urgent problems for public mental health service providers and policy-makers and provide more solutions for them.

Long-acting Injectable Antipsychotics during the COVID-19 pandemic in schizophrenia: An observational study in a real-world clinical setting

The COVID-19 pandemic is having an important impact on the practice of mental health services and on schizophrenia patients, and heterogeneous and conflicting findings are being reported on the reduction of long-acting injectable (LAI) antipsychotics use.Aims of the study were to assess the total number of patients treated with LAI, the start of novel LAI and the discontinuation of LAI treatments, analyzing register data of the first year of the pandemic, 2020, compared to a pre-pandemic reference year, 2019.Data from two outpatient centers were retrieved, for a total of 236 participants in 2020: no significant differences were observed comparing 2020 and 2019 when considering the total number of patients on LAI treatment (p = 0.890) and the number of dropouts (p = 0.262); however, a significant reduction in the start of LAI was observed (p = 0.022). In 2020, second generation LAI were more prescribed than first generation LAI (p = 0.040) while no difference was observed in 2019 (p = 0.191).These findings attest the efficacy of measures adopted in mental health services to face the consequences of COVID-19 and shed further light on the impact of the pandemic on the clinical practice of mental health services and on the continuity of care of people with schizophrenia.

Clinical and economic impact of long-acting injectable antipsychotics in patients previously treated with short-acting oral antipsychotics.

BACKGROUND: Available literature supports the use of long-acting injectable (LAI) antipsychotics over short-acting oral (SAO) formulations. The majority of evidence is centered on patients with schizophrenia insured under the Medicaid benefit. OBJECTIVE: To assess real-world clinical and economic outcomes of LAI compared with SAO antipsychotics in patients with psychiatric conditions insured under commercial, health care exchange, or Medicare plans. METHODS: In this exploratory treatmenteffectiveness study, a retrospective, before and after study design was used to evaluate differences in clinical and economic outcomes in patients switching from SAO to LAI antipsychotics. Patients who had at least 1 claim for an LAI antipsychotic and a psychiatric diagnosis were considered eligible for the study if they were continuously enrolled in a commercial, health care exchange, or Medicare plan for 12 months before (preperiod) and 12 months after (postperiod) their first LAI antipsychotic claim. During the preperiod, patients were required to have filled at least a 30-day supply of any SAO antipsychotic medication. Clinical outcomes included health care resource utilization (eg, hospitalizations per member per year [PMPY]), adherence measures, and medication switch trends. Economic outcomes included total per member per month (PMPM) spending across the medical benefit alone, the pharmacy benefit alone, and the combined spending across both benefits. Additionally, we examined patient costs and health plan spending within each of these categories. RESULTS: There was a significant decrease in overall hospitalizations PMPY (1.80 vs 0.88; P < 0.001) and psychiatric hospitalizations PMPY (0.65 vs 0.20; P <0.001) when comparing patients treated with SAO antipsychotics in the preperiod to the same patients treated with LAI antipsychotics in the postperiod, respectively. No differences were observed in the percentage of days covered with SAO and LAI agents (87.4% vs 85.8%; P=0.312). More patients switched between SAO antipsychotics during the preperiod, as compared with the number who switched between LAI antipsychotics during the postperiod (57.4% vs 10.3%; P < 0.001). On average, patients switched medications sooner in the preperiod vs the postperiod (114.50 vs 211.26 days; P < 0.001). No difference was observed between the preperiod and postperiod in total spending PMPM ($3,798.76 vs $3,702.63; P = 0.826) CONCLUSIONS: Patients switching from SAO to LAI antipsychotics experienced fewer hospitalizations, with no change in overall spending. Adherence was similar, though fewer medication switches occurred and there was a longer time before switching medications with LAI compared with SAO antipsychotics DISCLOSURES: Funding for this study was provided by Highmark Inc., but the sponsor had no role in the study outside the final review of the submitted manuscript.

Surface analysis of sequential semi-solvent vapor impact (SAVI) for studying microstructural arrangements of poly(lactide-co-glycolide) microparticles.

Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles have been used as long-acting injectable (LAI) drug delivery systems for more than three decades. Despite extensive use, few tools have been available to examine and compare the three-dimensional (3D) structures of microparticles prepared using different compositions and processing parameters, all collectively affecting drug release kinetics. Surface analysis after sequential semi-solvent impact (SASSI) was conducted by exposing PLGA microparticles to different semi-solvent in the liquid phase. The use of semi-solvent liquids presented practical experimental difficulties, particularly in observing the same microparticles before and after exposure to semi-solvents. The difficulties were overcome by using a new sequential semi-solvent vapor (SSV) method to examine the morphological changes of the same microparticles. The SASSI method based on SSV is called surface analysis of semi-solvent vapor impact (SAVI). Semi-solvents are the solvents that dissolve PLGA polymers depending on the polymer's lactide:glycolide (L:G) ratio. A sequence of semi-solvents was used to dissolve portions of PLGA microparticles in an L:G ratio-dependent manner, thus revealing different structures depending on how microparticles were prepared. Exposing PLGA microparticles to semi-solvents in the vapor phase demonstrated significant advantages over using semi-solvents in the liquid phase, such as in control of exposure conditions, access to imaging, decreasing the time for sequential exposure of semi-solvents, and using the same microparticles. The SSV approach for morphological analysis provides another tool to enhance our understanding of the microstructural arrangement of PLGA polymers. It will improve our comprehensive understanding of the factors controlling drug release from LAI formulations based on PLGA polymers.

Projected Impact of Expanded Long-Acting Injectable PrEP Use Among Men Who Have Sex With Men on Local HIV Epidemics.

Pre-exposure prophylaxis (PrEP) is a key component in helping to reduce HIV incidence in the United States. Long-acting injectable (LAI) PrEP is a new alternative to oral PrEP; its potential to affect local HIV epidemics remains unclear. The Johns Hopkins HIV Economic Epidemiological model (JHEEM) is a dynamic model of HIV transmission in 32 US urban areas. We used JHEEM to project the HIV incidence among men who have sex with men (MSM) from 2020 to 2030 under a range of interventions aimed at increasing PrEP use. In the absence of any intervention (ie, current levels of oral PrEP and HIV care engagement), we projected a 19% reduction (95% credible interval, CrI 1% to 36%) in HIV incidence among MSM from 2020 to 2030 across all 32 cities. Adding 10% LAI PrEP uptake (above a base case of all oral PrEP) reduced the incidence by 36% (95% CrI 23% to 50%) by year 2030. This effect varied between cities, ranging from 22% in Atlanta to 51% in San Francisco. At 25% additional LAI PrEP uptake, this incidence reduction increased to 54% (95% CrI 45% to 64%). Reductions in incidence after introducing LAI PrEP were driven primarily by increased uptake and sustained usage rather than increased efficacy. LAI PrEP has the potential to substantially reduce HIV incidence among MSM, particularly if it increases PrEP uptake and continued use beyond existing levels. Because potential effects vary by city, the effectiveness of expanding PrEP use is dependent on local dynamics.

Frequency of genotypic factors possibly associated with cabotegravir/rilpivirine failure in antiretroviral treatment-naïve and -experienced HIV-1- infected population.

The long-acting injectable (LAI) cabotegravir (CAB) and rilpivirine (RPV) treatment offers important advantages over oral ART (antiretroviral therapy), however baseline factors possibly contributing to the CAB/RPV treatment failure were identified. The purpose of this study was to describe the frequency of virologic factors previously influencing efficacy of this treatment, namely RPV and CAB resistance-associated mutations (RAMs) and A1/A6 subtype among naïve and treatment-experienced HIV-1-infected patients from Poland. The following datasets of HIV-1 sequences were analysed: 4809 protease and reverse transcriptase (PR/RT) sequences obtained from 4649 Polish Caucasian patients (4122 naive and 687 non-naïve) supplemented with integrase (PR/RT/INT) sequences in 1217 cases (942 naïve and 275 non-naïve). Sub-subtypes A were assigned by phylogenetic methods. Major and minor CAB and RPV RAMs were determined according to the IAS-USA 2019 list, while minor RAMs were additionally defined based on the Stanford database algorithm. Subtype A1/A6 frequency ranged from 6.11% in ART failing cases with PR/RT sequences only, to 15.92% for the PR/RT/INT treatment-naïve dataset, while RPV RAMs were found in up to 5.89% of treatment-naïve and 14.56% of ART failing cases. Regardless treatment history, only <1% sequences had combination of two factors (RPV RAMs and A1/A6 subtype). Furthermore, CAB RAMs were found in 1.27% of treatment-naïve and 14.54% of experienced patients. Despite notable frequency of subtype A1/A6 or CAB/RPV RAMs analysed separately, combination of at least two factors previously associated with failure or this treatment is rare. As subtype A1/A6 becomes more common across real-life cohorts continued subtyping and RAM screening will remain of key importance for LAI treatment implementation. Sequence data from this article have been deposited in GenBank under accession numbers: GU906860, GU906864, GU906871-GU906874, JQ305750-JQ305791, KC409134-KC409222, KM057341-KM057362, KM283892-KM284490, KT340108-KT340205, MZ468643-MZ468894, MZ671788-MZ671823, OP298017-OP302727.

A Real-World Observational Study of the Use and Associated Costs of Treating Neuroendocrine Tumors With Somatostatin Analogs in Canada.

Somatostatin analogs (SSAs; lanreotide autogel and octreotide long-acting release) are used to treat neuroendocrine tumors; however, factors that influence SSA use are unclear. This real-world, observational study collected data from private/public pharmacy claims for patients using SSAs in Canada. Data relating to dosing regimens, injection burden, treatment persistence, and costs were retrospectively analyzed for treatment-naive patients. Overall, 1545 patients were included in the analysis of dosing regimens, 908 for injection burden, 453 for treatment persistence, and 903 for treatment-associated costs. Compared with lanreotide, treatment with octreotide long-acting release was more likely associated with treatment above the maximum recommended dose (odds ratio, 16.2; 95% confidence interval, 4.3-136.2; P < 0.0001), higher weighted average long-acting SSA injection burden (13.4 vs 12.5, P < 0.0001), and a higher number of rescue medication claims per patient (0.22 vs 0.03, P < 0.0001). Treatment with lanreotide autogel was associated with greater treatment persistence (hazard ratio, 0.58; 95% confidence interval, 0.42-0.80; P = 0.001) and lower mean annual costs of treatment than octreotide long-acting release (Canadian dollars $27,829.35 vs $31,255.49; P < 0.0001). These findings provide valuable insight into SSA use in clinical settings and may inform treatment selection.

BEYOND THE BASICS: PRESCRIBING PRACTICES AND CLINICAL CHALLENGES IN EARLY PSYCHOSIS

Thoughtful prescribing for young people experiencing early psychosis can build a foundation that can positively impact recovery and outcomes. Clinicians sometimes must navigate prescribing challenges including treatment nonadherence, polypharmacy, and medication intolerability. This presentation will discuss complexities within pediatric and transitional-age youth psychopharmacology as it relates to early psychosis, including utilization of long-acting injectables, clozapine, recognition of important cytochrome p450 interactions, and principles of prescribing in this population.

Study finds LAI antipsychotics linked with lower risk of hospitalization

A population‐based study based in Hong Kong has found that long‐acting injectable (LAI) antipsychotics were associated with lower risk of hospitalization than oral antipsychotics in patients with schizophrenia. There was no significant difference between LAI and oral antipsychotics in the frequency of emergency department visits.

Poly(Lactic Acid) Block Copolymers with Poly(Hexylene Succinate) as Microparticles for Long-Acting Injectables of Risperidone Drug.

In the present work, Risperidone microparticles from poly(lactic acid)/poly(hexylene succinate) (PLA-b-PHSu) block copolymers in different ratios, 95/05, 90/10 and 80/20 w/w, were examined as long-acting injectable formulations. Nuclear magnetic resonance (NMR) was used to verify the successful synthesis of copolymers. Enzymatic hydrolysis showed an increase in weight loss as the content of PHSu increased, while the cytotoxicity studies confirmed the biocompatibility of the copolymers. The polyesters were further used to encapsulate Risperidone by spray drying. The drug-loaded microparticles were studied by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD). SEM microphotographs confirmed that spherically shaped microparticles were prepared with sizes about 5–12 μm, while XRD and differential scanning calorimetry (DSC) studies evidenced that Risperidone was encapsulated in amorphous form. The drug loading and the entrapment efficiency of Risperidone were studied as well as the in vitro release from the prepared microparticles. As the content of PHSu increased, a higher release of Risperidone was observed, with PLA-b-PHSu 80/20 w/w succeeding to release 100% of RIS within 12 days. According to theoretical modeling, the kinetics of RIS release from PLA-b-PHSu microparticles is complex, governed by both diffusion and polymer erosion.

LAI antipsychotics associated with lower risk of TD than oral versions

A study that was based on a review of adverse drug event reports in Japan has concluded that long‐acting injectable (LAI) antipsychotics appear to be associated with lower risk of tardive dyskinesia (TD) than their oral counterparts. TD also was less common with use of second‐generation LAI antipsychotics compared with first‐generation drugs.

Determining bioequivalence possibilities of long acting injectables through population PK modelling

Long acting injectables (LAI) products are a popular intervention for treating a number of chronic conditions, with their long drug release reducing the administration frequency and thus improving patient adherence. The extended release, however, can provide a major challenge to bioequivalence (BE) testing since the long absorption half-life results in a long washout period, meaning that a traditional BE study can be many months or years in length. The unique PK profile for LAI products also means that it is critical to have appropriate metrics to summarise the plasma concentration profile. In this work, we use paliperidone as a case study to demonstrate how Population PK modelling can be utilised to explore sensitivity of summary metrics to different products. We also determine a range of products that are bioequivalent after both multiple dosing and single dosing. Finally, we show how the modelling can be used in a (virtual) PK study as an alternative approach to determining bioequivalence. This work demonstrates the potential for Population PK modelling in bioequivalence assessment, opening doors to more streamlined product development.

Spray-dried tenofovir alafenamide-chitosan nanoparticles loaded oleogels as a long-acting injectable depot system of anti-HIV drug

The development of suitable drug delivery systems for prolonged action against HIV receives great attention in recent research. Herein, a long-acting injectable (LAI) of Tenofovir alafenamide-chitosan polymeric nanoparticles loaded oleogels developed with sesame oil and ethyl cellulose for prolonged release of the drug is reported for the first time. The research resulted with unique long-acting parenteral formulation for chronic anti-retroviral therapy, based on our experimental in-vitro and ex-vivo studies. The chitosan nanoparticles with 49 % drug content were produced through the spray-drying technique and characterized for their size (106–540 nm) and the other physico-chemical features through SEM, FT-IR, XRD, TGA, and DSC. The ethyl cellulose and sesame oil oleogels were developed through a heat-cool process by incorporating the drug-loaded chitosan nanoparticles. The oleogels exhibited extended release (56 %) of the drug for 16 days, which could be prolonged further to achieve the maximum drug release. Also, the ex-vivo permeation studies of the nanoparticles loaded oleogels demonstrated about 10-fold decrease in the flux and the permeation of the drug due to prolonged release of the drug across dual barriers of chitosan nanoparticles and ethyl cellulose gel matrix. The result provided proof-of-evidence that the developed Tenofovir alafenamide-chitosan polymeric nanoparticles loaded with ethyl cellulose oleogels could be potentially used as the long-acting injectable system for the treatment of patients infected with HIV/AIDS.

"She is the one who knows": A qualitative exploration of oral and injectable PrEP as part of a community empowerment approach to HIV prevention among female sex workers in the Dominican Republic and Tanzania.

Despite documented interest among female sex workers (FSW), uptake of oral pre-exposure prophylaxis (PrEP) for HIV prevention has been low. Recent trials and regulatory approval of long-acting injectable (LAI) PrEP offer new hope for the potential of this biomedical intervention. We examined FSW's PrEP-related interest and preferences regarding both oral and LAI PrEP situating these dynamics within their specific social and occupational realities. We conducted this work using qualitative methods across two distinct contexts by conducting 40 in-depth interviews with FSW in Tanzania and the Dominican Republic. Textual data was coded using iterative thematic content analysis. Analytic summaries were developed and reviewed to identify recurring themes. We systematically organized themes within each country and then compared across settings. Women in both settings expressed strong interest in PrEP seeing it as an important option to protect themselves in their work. Most participants preferred LAI PrEP due to expectations of reduced stigma and concerns about daily pill adherence and side effects. Occupational factors such as alcohol use, overnight dates with clients, and fear of violence from clients were identified as barriers to daily oral PrEP. LAI PrEP was seen as having the potential to reduce stress related to oral PrEP. Women who preferred pills discussed fear of needles, skepticism about the injections, and others relayed that taking a daily pill would not be challenging for them. There was a pre-dominant sentiment that women know best whether they are better suited for oral or LAI PrEP. Participants stressed the importance of FSW understanding both options to ensure informed decision-making around PrEP and described community-led peer education as key to delivering trusted information. Community empowerment approaches led by FSW which address structural and psychosocial constraints and promote safe work environments may facilitate equitable access and uptake of PrEP among FSW across settings.

A Patient Decision Aid (i.ARTs) to Facilitate Women's Choice Between Oral and Long-Acting Injectable Antiretroviral Treatment for HIV: Protocols for its Development and Randomized Controlled Pilot Trial.

BackgroundMany women with HIV (WWH) have suboptimal adherence to oral antiretroviral therapy (ART) due to multilevel barriers to HIV care access and retention. A long-acting injectable (LAI) version of ART was approved by the US Food and Drug Administration in January 2021 and has the potential to overcome many of these barriers by eliminating the need for daily pill taking. However, it may not be optimal for all WWH. It is critical to develop tools that facilitate patient-provider shared decision making about oral versus LAI ART modalities to promote women’s adherence and long-term HIV outcomes.ObjectiveThis study will develop and pilot test a web-based patient decision aid called i.ART+support (i.ARTs). This decision aid aims to support shared decision making between WWH and their providers, and help women choose between oral and LAI HIV treatment.MethodsThe study will occur in 3 phases. In phase 1, we will utilize a mixed methods approach to collect data from WWH and medical and social service providers to inform i.ARTs content. During phase 2, we will conduct focus groups with WWH and providers to refine i.ARTs content and develop the web-based decision aid. In phase 3, i.ARTs will be tested in a randomized controlled trial with 180 women in Miami, Florida, and assessed for feasibility, usability, and acceptability, as well as to evaluate the associations between receiving i.ARTs and viral suppression, ART pharmacy refills, and clinic attendance.ResultsThis study was funded in March 2021. Columbia University’s IRB approved the study protocols (approval number IRB-AAAT5314). Protocols for phase 1 interviews have been developed and interviews with service providers started in September 2021. We will apply for Clinicaltrials.gov registration prior to phase 3, which is when our first participant will be enrolled in the randomized controlled trial. This is anticipated to occur in April 2023.ConclusionsThis study is the first to develop a web-based patient decision aid to support WWH choices between oral and LAI ART. Its strengths include the incorporation of both patient and provider perspectives, a mixed methods design, and implementation in a real-world clinical setting.International Registered Report Identifier (IRRID)DERR1-10.2196/35646

Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation.

Long-acting injectables are a unique drug formulation strategy, providing a slow and sustained release of active pharmaceutical ingredients (APIs). In this study, a novel approach that combines liquid antisolvent precipitation with seeding to obtain a stable form of the API indomethacin while achieving the desired particle size distribution is described. It was proven that when a metastable form of indomethacin was initially nucleated, the rate of its transformation to the stable form was influenced by the presence of excipients and seeds (17.10 ± 0.20 μm), decreasing from 48 to 4 h. The final particle size (D50) of the indomethacin suspension produced without seeding was 7.33 ± 0.38 μm, and with seeding, it was 5.61 ± 0.14 μm. Additionally, it was shown that the particle size distribution of the seeds and the time point of seed addition were critical to obtain the desired solid-state form and that excipients played a crucial role during nucleation and polymorphic transformation. This alternative, energy-efficient bottom-up method for the production of drug suspensions with a reduced risk of contamination from milling equipment and fewer processing steps may prove to be comparable in terms of stability and particle size distribution to current industrially accepted top-down approaches.

Second-Generation Antipsychotic Long-Acting Injection Reduced the Time of Restrictive Interventions in Patients With Schizophrenia: Retrospective, A 4-Year Mirror-Image Study.

Whether second-generation antipsychotic long-acting injection (SGA-LAI) reduces psychotic symptoms at relapse compared with oral antipsychotics remains unclear. The present study investigated the effects of SGA-LAI on the time (in hours) of restrictive interventions in hospitalization by conducting a retrospective observational 4-year mirror-image study at a single medical center in Japan. We performed a retrospective observational mirror-image study conducted between November 2013 and January 2018. Data were initially retrieved from 101 patients. The 38 patients with schizophrenia who met the inclusion criteria were enrolled in the analysis. The primary outcome was the time of restrictive interventions and the secondary outcomes included the number of hospitalizations (total, voluntary, and involuntary) and bed days compared 2 years before and after initiating SGA-LAI. The restrictive interventions were defined as seclusion and physical restraints. The mean time of restrictive interventions significantly decreased from 43.7 to 3.03 ( P = 0.021). The number of admissions and the total number of bed days in post-SGA-LAI fell from 1.03 to 0.61 ( P = 0.011) and 130 to 39.3 ( P = 0.003), respectively, compared with pre-SGA-LAI. In particular, the number of involuntary admissions was significantly reduced (0.50-0.26, P = 0.039). The findings indicate that SGA-LAI reduced the time of restrictive interventions and the number of involuntary admissions. Moreover, SGA-LAI may contribute to mild psychiatric symptoms during relapse.

1386P 1/2a study of PRL-02, a long-acting IM depot injection of abiraterone decanoate in patients with prostate cancer (NCT04729114)

PRL-02 is a long-acting IM depot injection of abiraterone decanoate, a novel prodrug of abiraterone. In non-clinical models PRL-02 provides high and durable concentrations of prodrug and abiraterone in target tissues and organs (including adrenal, lymph and bone). Single doses of PRL-02 markedly depressed testosterone (T) through 14 weeks in a castrate monkey model to levels comparable to clinical results with oral abiraterone acetate (AA) but with lower and less variable plasma exposures. The totality of nonclinical data study results suggests that PRL-02 has the potential for a superior therapeutic index and safety profile compared to oral AA.