Doria (risperidone extended release) / ROVI Pharmaceuticals Laboratories - LARVOL DELTA

Clinical Utility of Long-Acting Injectable Risperidone in Schizophrenia and Bipolar I Disorder: A Review of Clinical Studies. (PubMed, Psychol Res Behav Manag) - "To date, five different risperidone LAI formulations have been marketed - including a second biweekly microsphere injection (LY03004), a newer monthly intramuscular formulation using in situ microparticles (ISM) technology that does not require an oral risperidone run-in, and two subcutaneous formulations (RBP-7000 and TV-46000)...To facilitate this, healthcare providers should develop a comprehensive understanding of these formulations to select the most suitable option. While risperidone ISM, RBP-7000, and TV-46000 may enhance treatment feasibility and adherence, further research is needed to build an evidence base comparable to that available for BW-RLAI, particularly in the treatment of BD."

Journal • Review • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

RESHAPE: Non-interventional Study of Risperidone ISM® in Schizophrenia Patients Hospitalised Due to a Relapse (clinicaltrials.gov) - P=N/A | N=275 | Completed | Sponsor: Rovi Pharmaceuticals Laboratories | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

Pharmacokinetic characteristics of risperidone ISM for the treatment of schizophrenia. (PubMed, Expert Opin Drug Metab Toxicol) - "Risperidone-ISM achieves therapeutic blood levels within 12-48 hours after a single injection, currently lasting for 1 month, easing the initiation of a LAI risperidone formulation in adults with schizophrenia where LAIs remain underutilized. Prescriptions of LAIs, including risperidone-ISM, are likely to increase with an improved understanding of pharmacokinetic profiles and patient acceptability and outcomes, including in real-world settings informing drug selection."

Journal • PK/PD data • Review • CNS Disorders • Psychiatry • Schizophrenia

Evaluating the Real-World Pharmacokinetics of Risperidone ISM® in Routine Clinical Practice. (PubMed, Biomedicines) - " Risperidone ISM® achieves rapid and sustained therapeutic plasma levels, offering significant benefits in schizophrenia treatment. However, the high interindividual variability observed must be thoroughly studied, and the contributing factors identified to ensure the therapy is as effective and safe as possible."

Journal • PK/PD data • Real-world evidence • CNS Disorders • Psychiatry • Schizophrenia

RESHAPE: Non-interventional Study of Risperidone ISM® in Schizophrenia Patients Hospitalised Due to a Relapse (clinicaltrials.gov) - P=N/A | N=277 | Active, not recruiting | Sponsor: Rovi Pharmaceuticals Laboratories | Recruiting ➔ Active, not recruiting | N=1200 ➔ 277 | Trial completion date: Dec 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Risperidone In Situ Microparticles: A Review in Schizophrenia. (PubMed, Drugs) - "Risperidone ISM® was generally well tolerated in clinical trials, with a safety profile consistent with that of oral risperidone. Its fast onset of action, without the need for oral supplementation or loading doses, makes risperidone ISM® a promising long-acting injectable that could enhance treatment adherence."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Risperidone ISM®: review and update of its usefulness in all phases of schizophrenia. (PubMed, Ther Adv Psychopharmacol) - "Improvement and maintenance of personal and social functioning and health-related quality of life were observed in each setting, respectively. All these findings endorse Risperidone ISM as a useful and valuable treatment for the acute and maintenance management of patients with schizophrenia."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Exposure-Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM. (PubMed, J Clin Pharmacol) - "Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations."

Journal • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Preliminary experience in a "real world" setting with risperidone ISM for the treatment of acute patients affected by schizophrenia (ECNP 2024) - "Our preliminary data showed that Risperidone ISM is effective and well tolerated for the treatment of acute psychotic relapse also in a "real world" setting, confirming the Results of RCT and OLE studies and placing it among the AP LAI first-options in schizophrenia."

Clinical • Real-world • Real-world evidence • CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia • Schizophreniform Disorder

RESHAPE: Non-interventional Study of Risperidone ISM® in Schizophrenia Patients Hospitalised Due to a Relapse (clinicaltrials.gov) - P=N/A | N=1200 | Recruiting | Sponsor: Rovi Pharmaceuticals Laboratories | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Development of a population pharmacokinetic model for the novel long-acting injectable antipsychotic risperidone ISM®. (PubMed, Br J Clin Pharmacol) - "The population PK model adequately described active moiety concentrations from five clinical studies after risperidone ISM® administration. Relationships between active moiety exposure and covariates were defined in order to facilitate simulations for future studies. The model showed that risperidone ISM® rapidly achieves therapeutic plasma levels within the first hours after the first injection that are maintained sustainedly throughout the whole dosing interval following once-monthly gluteal injections of 100 mg and 75 mg."

Journal • PK/PD data • CNS Disorders • Psychiatry • Schizophrenia

Clinical experience with once-monthly risperidone ISM in a mental health center. A retrospective study. (EPA 2024) - "Among the switches made to monthly risperidone, 69,2% (n=9) were previously treated with oral risperidone, 15,4% (n=2) were treated with once-biweekly risperidone long-acting injectable, 7,9% (n=1) with oral paliperidone and 7,9% with aripiprazole monthly injectable. In the sample analyzed, once-monthly Risperidone ISM had reasonable tolerance levels. Also, it´s shown to be effective in preventing psychotic decompensations and hospital admissions. Therefore, this new injectable of monthly risperidone represents a therapeutic alternative to consider in order to guarantee therapeutic adherence and improve the quality of life of patients with psychotic symptoms."

Retrospective data • CNS Disorders • Dystonia • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • Schizophrenia

QUARTZ: Pharmacokinetics, Safety and Tolerability of Different Formulations and Dose Strengths of Quarterly Risperidone (QUAR) in Patients With Schizophrenia (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Rovi Pharmaceuticals Laboratories

New P1 trial • CNS Disorders • Psychiatry • Schizophrenia

Pharmacokinetic/pharmacodynamic modeling and simulation of dopamine D2-receptor occupancy-time profiles comparing Risperidone ISM versus daily oral risperidone (ECNP 2023) - "Simulated D2RO profiles revealed that Risperidone ISM (100 mg) provides a similar likelihood of clinical response (D2RO above 65%) than the equivalent 4mg oral risperidone, and even when comparing with higher doses of 6 or 8 mg QD, assuming a perfect adherence. Moreover, Risperidone ISM shows superiority for the real clinical practice of medium or bad oral treatment compliance. Thus, Risperidone ISM 100 mg is adequate to achieve a similar or improved D2RO occupancy level than higher doses of oral risperidone and thus could be satisfactorily switched for maintenance treatment of adult patients treated with 4 mg or higher oral risperidone doses."

PK/PD data • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Pharmacokinetic/pharmacodynamic modeling and simulation of dopamine D2-receptor occupancy-time profiles comparing monthly risperidone ISM versus monthly paliperidone palmitate (ECNP 2023) - "Simulated D2RO profiles revealed that Risperidone ISM (100 mg) provides higher likelihood of clinical response (D2RO above 65%) than PP1M (150 mg maintenance dose), especially during the first 4 months after initiation of LAI antipsychotic treatment. Thus, Risperidone ISM can be an effective therapeutic strategy for a rapid and sustained symptom reduction in patients with an acute relapse of schizophrenia."

PK/PD data • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Risperidone ISM effectiveness in schizophrenia patients hospitalised due to a relapse: a prospective non-interventional evaluation. design of the reshape study (ECNP 2023) - P=N/A | "The RESHAPE study will provide real-world data on the use of Risperidone ISM for the treatment of adult patients who are hospitalised due to a schizophrenia relapse. Additionally, it will show the way these patients are managed under usual clinical practice conditions by psychiatrists from several European countries."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Extrapyramidal adverse events and anticholinergics use after the long-term treatment of patients with schizophrenia with the new long-acting antipsychotic Risperidone ISM: results from matching-adjusted indirect comparisons versus once-monthly formulations of Paliperidone palmitate and Aripiprazole monohydrate in 52-week studies. (PubMed, Ann Gen Psychiatry) - "This MAIC is consistent with the safety and tolerability results obtained during the PRISMA-3 clinical trial in the long-term treatment of schizophrenia and suggests a favorable safety and tolerability profile in terms of EPS incidence and anticholinergic agent use, relative to other antipsychotic therapies used for treatment of patients with schizophrenia in the maintenance setting."

Adverse events • Journal • CNS Disorders • Psychiatry • Schizophrenia

Switching to Long-Acting Injectable Antipsychotics: Pharmacological considerations and practical approaches. (PubMed, Expert Opin Pharmacother) - "Recent improvements include a one-day initiation option for aripiprazole lauroxil, aripiprazole once-monthly, risperidone in situ microparticles and subcutaneous risperidone. Future LAI developments should focus on longer dosing intervals, subcutaneous administration, expansion of LAIs beyond currently available antipsychotic agents and indications beyond schizophrenia and bipolar disorder. In the future, LAIs might become a first-line treatment after initial oral stabilization for chronic mental disorders with need for maintenance treatment and presence of significant non-adherence."

Journal • Review • Bipolar Disorder • CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

Personal and Social Functioning and Health-Related Quality of Life in Patients with Schizophrenia Treated with the Long-Acting Injectable Antipsychotic Risperidone ISM. (PubMed, Neuropsychiatr Dis Treat) - "These findings, along with a fast onset of efficacy, could contribute to reinforcing the therapeutic alliance and possibly an earlier discharge. Moreover, patient functioning continued improving or was maintained with long-term treatment."

HEOR • Journal • CNS Disorders • Psychiatry • Schizophrenia

Achieving long-term goals through early personalized management of schizophrenia: expert opinion on the role of a new fast-onset long-acting injectable antipsychotic. (PubMed, Ann Gen Psychiatry) - "Risperidone ISM has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

RESHAPE: Non-interventional Study of Risperidone ISM® in Schizophrenia Patients Hospitalised Due to a Relapse (clinicaltrials.gov) - P=N/A | N=1200 | Recruiting | Sponsor: Rovi Pharmaceuticals Laboratories | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Extrapyramidal safety and tolerability profile of the new long-acting antipsychotic Risperidone ISM for the treatment of patients with schizophrenia (ECNP 2022) - P3 | "Mean change from baseline to end-of-treatment in the EPS-related scores over the 12-week DB and 1-year OLE phases   PLACEBO RISPERIDONE-ISM 75 mg  RISPERIDONE-ISM 100 mg ALL RISPERIDONE ISM  DB PHASE  N = 147  N = 144  N = 146  N = 290 AIMS, Mean (SD) 0.1 (1.36)-0.1 (1.98)-0.1 (1.22)-0.1 (1.64) BARS, Mean (SD) 0.1 (0.98)0.0 (0.59)0.1 (0.87)0.1 (0.75) SAS, Mean (SD) 0.1 (2.51)0.1 (0.75)0.0 (1.17)0.1 (0.98) OLE PHASE   NA  N = 116  N = 99  N = 215 AIMS, Mean (SD) NA0.3 (1.73)0.2 (1.07)0.3 (1.47) BARS, Mean (SD) NA0.1 (0.38)0.2 (0.64)0.1 (0.52) SAS, Mean (SD) NA0.3 (1.06)0.3 (0.76)0.3 (0.93) Conclusion : A low incidence of EPS-related TEAEs was observed during the acute and maintenance treatment with long-acting Risp-ISM in patients with schizophrenia. Furthermore, a low percentage of patients used anticholinergic or beta-blocking agents..."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Cardiovascular safety profile of the long-acting antipsychotic Risperidone ISM in patients with schizophrenia treated in a phase 3 clinical trial (ECNP 2022) - P3 | "Patients with treatment-related cardiovascular adverse events and change from baseline (CFB) at endpoint on QT parameters reported over the 12-week Double-Blind (DB) and 1-year Open-Label Extension (OLE) phases of PRISMA-3 Study  PLACEBO RISPERIDONE ISM 75 mg  RISPERIDONE ISM 100 mg  ALL RISPERIDONE ISM   DB PHASE  N=147N=144N=146N=290 Sinus bradycardia, N (%)001 (0.7)1 (0.3) Tachycardia01 (0.7)3 (2.1)4 (0.9) QT Interval CFB, Single Beat (msec), Mean (SD)5.7 (26.08)6.9 (28.98)5.1 (25.83)6.0 (27.44) QTcB Interval CFB, Single Beat (msec), Mean (SD)3.3 (21.71)6.2 (19.97)1.0 (17.34)3.6 (18.87) QTcF Interval CFB, Single Beat (msec), Mean (SD)4.1 (16.91)6.5 (14.68)2.3 (14.07)4.4 (14.51)  OLE PHASE NAN = 116N = 99N = 215 Sinus thachycardia, N (%)NA1 (0.9)01 (0.5) Tachycardia, N (%)NA02 (2.0)2 (0.9) QT Interval CFB, Single Beat (msec), Mean (SD)NA-1.1 (27.94)1.8 (22.99)0.2 (25.79) QTcB Interval CFB,..."

Clinical • P3 data • CNS Disorders • Psychiatry • Schizophrenia

Efficacy of Risperidone ISM in patients with an acute exacerbation of schizophrenia: a post-hoc analysis on the PANSS-6 score (ECNP 2022) - P3 | "Mean change in PANSS-6 and PANSS-30 scores from baseline to Day 85 in the phase III study “PRISMA-3” PLACEBO N = 132  RISPERIDONE ISM 75 mg   N = 129  RISPERIDONE ISM 100 mg   N = 129  PANSS-6 Mean (SD) score baseline22.8 (2.60)22.7 (3.09)22.6 (2.83) LS Mean change from baseline to Day 85 (95% CI)*-2.9 (-3.7 to -2.1)-5.8 (-6.6 to -5.0)-5.9 (-6.8 to -5.1) Difference versus placebo (95% CI)--2.9 (-4.1 to -1.7)-3.0 (-4.2 to -1.9) P-value-<0.001<0.001 PANSS-30 [1] Mean (SD) score baseline96.4 (7.21)96.3 (8.47)96.1 (8.42) LS Mean change from baseline to Day 85 (95% CI)*-11.0 (-14.1 to -8.0)-24.6 (-27.5 to -21.6)-24.7 (-27.7 to -21.6) Difference versus placebo (95% CI)--13.0 (-17.3 to -8.8)-13.3 (-17.6 to -8.9) P-value-<0.0001<0.0001 * Analysis by a mixed model repeated measures approach.   Conclusion : PANSS-6 Result s were consistent with the previously published Result s of..."

Clinical • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

Risperidone ISM as a New Option in the Clinical Management of Schizophrenia: A Narrative Review. (PubMed, Adv Ther) - "There is clinical evidence that these results are maintained in the long term. In conclusion, four-weekly risperidone ISM (75 mg and 100 mg) is an adequate antipsychotic for treating schizophrenia, both in the short term when an exacerbation has recently occurred and for long-term maintenance, since it provides rapid onset of action and sustained efficacy, as well as being safe and well tolerated."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia