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Introduction <p>TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension suitable for subcutaneous administration from a prefilled syringe. The objective of the current analysis was to characterize the pharmacokinetics (PK) of TV-46000 based on pooled data from phase&#xa0;1 and phase&#xa0;3 studies, and to further support clinical use aspects of TV-46000.</p> Methods <p>A population PK (popPK) model was developed using TV-46000 PK data obtained from three phase&#xa0;1 studies (<i>n</i> = 267) and two phase&#xa0;3 trials (<i>n</i> = 425). A sequential parent–metabolite model structure was used, and the total active moiety (TAM) concentration–time profiles were simulated for TV-46000 once monthly (q1m) and once every 2&#xa0;months (q2m) across the range of available doses and different administration sites.</p> Results <p>The popPK model adequately characterized the PK of risperidone and its active metabolite. TV-46000 reaches therapeutic plasma TAM concentrations (≥ 10&#xa0;ng/mL) within 24&#xa0;h following first dose administration. Three months after initiation of TV-46000, 86% and 88% of steady-state TAM exposure were achieved for q1m and q2m, respectively, and steady state was fully attained by 6&#xa0;months (i.e., &gt; 90% of steady-state TAM exposure). In addition, simulated D2 receptor occupancy for TV-46000 was generally within the therapeutic window of 60–80% during both dosing intervals.</p> Conclusions <p>The developed popPK model, together with corresponding simulations, supports TV-46000 as a LASCA that offers flexible dosing intervals (q1m or q2m) and administration sites (abdomen or upper arm) and does not require oral supplementation or loading dose(s).</p>

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Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia

  • 期刊论文

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  • 发表日期：

    2025年3月23日

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  • Itay Perlstein,
  • Avia Merenlender Wagner,
  • Anna Elgart,
  • Anthe S. Zandvliet,
  • Farina Hellmann,
  • YuWei Lin,
  • Eline van Maanen,
  • Nele Plock,
  • Floris Fauchet,
  • Rajendra Singh

摘要

Introduction

TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension suitable for subcutaneous administration from a prefilled syringe. The objective of the current analysis was to characterize the pharmacokinetics (PK) of TV-46000 based on pooled data from phase 1 and phase 3 studies, and to further support clinical use aspects of TV-46000.

Methods

A population PK (popPK) model was developed using TV-46000 PK data obtained from three phase 1 studies (n = 267) and two phase 3 trials (n = 425). A sequential parent–metabolite model structure was used, and the total active moiety (TAM) concentration–time profiles were simulated for TV-46000 once monthly (q1m) and once every 2 months (q2m) across the range of available doses and different administration sites.

Results

The popPK model adequately characterized the PK of risperidone and its active metabolite. TV-46000 reaches therapeutic plasma TAM concentrations (≥ 10 ng/mL) within 24 h following first dose administration. Three months after initiation of TV-46000, 86% and 88% of steady-state TAM exposure were achieved for q1m and q2m, respectively, and steady state was fully attained by 6 months (i.e., > 90% of steady-state TAM exposure). In addition, simulated D2 receptor occupancy for TV-46000 was generally within the therapeutic window of 60–80% during both dosing intervals.

Conclusions

The developed popPK model, together with corresponding simulations, supports TV-46000 as a LASCA that offers flexible dosing intervals (q1m or q2m) and administration sites (abdomen or upper arm) and does not require oral supplementation or loading dose(s).