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Size matters: the importance of particle size in a newly developed injectable formulation for the treatment of schizophrenia

  • Rakesh Jain (a1), Jonathan Meyer (a2), Angela Wehr (a3), Bhaskar Rege (a3), Lisa von Moltke (a4) and Peter J. Weiden (a5)...

Abstract

One of the challenges with initiating long-acting injectable (LAI) antipsychotic regimens is achieving relevant drug levels quickly. After first injection of the LAI antipsychotic aripiprazole lauroxil (AL), the lag to reaching relevant plasma aripiprazole levels was initially addressed using supplemental oral aripiprazole for 21 days. A 1-day AL initiation regimen using a NanoCrystal® Dispersion formulation of AL (ALNCD; Aristada Initio®) combined with a single 30 mg dose of oral aripiprazole has been developed as an alternative approach. We compared the 1-day AL initiation regimen (ALNCD + 30 mg oral aripiprazole for 1 day) with the 21-day AL initiation regimen (AL + 15 mg/day of oral aripiprazole for 21 days) using kinetic modeling. Observed and modeled data demonstrate that the 1-day AL initiation regimen provides continuous aripiprazole exposure comparable to the 21-day AL initiation regimen. Each component of the 1-day AL initiation regimen (30 mg oral aripiprazole, ALNCD, and AL) contributes to aripiprazole plasma levels at different times, with oral aripiprazole predominating in the first week, then ALNCD and AL over time. In a double-blind, placebo-controlled, phase 1 study in patients with schizophrenia, the 1-day initiation regimen resulted in rapid achievement of relevant plasma aripiprazole levels comparable to those from the 21-day initiation regimen. Safety and tolerability of the 1-day regimen were consistent with the known profile of aripiprazole. Each part of the 1-day initiation regimen, together with AL, is necessary for continuous aripiprazole exposure from treatment initiation until the next regularly scheduled AL injection is administered.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

*Address correspondence to: Rakesh Jain, Department of Psychiatry, Texas Tech University School of Medicine, 2500 W. William Cannon Drive, Suite 505, Austin, TX 78745, USA. (Email: JainTexas@gmail.com)

Footnotes

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This study was sponsored by Alkermes, Inc. Medical writing and editorial support were provided by Kathleen M. Dorries, PhD, and John H. Simmons, MD, of Peloton Advantage, LLC (Parsippany, NJ, USA), and funded by Alkermes, Inc. The authors are entirely responsible for the scientific content of the paper.

Footnotes

References

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Size matters: the importance of particle size in a newly developed injectable formulation for the treatment of schizophrenia

  • Rakesh Jain (a1), Jonathan Meyer (a2), Angela Wehr (a3), Bhaskar Rege (a3), Lisa von Moltke (a4) and Peter J. Weiden (a5)...

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