https://orcid.org/0009-0007-1733-9640
Abstract
Background
In patients with schizophrenia, study design to optimize adherence and objective measurement of adherence is critical for interpreting results. Two randomized, double-blind studies evaluating adjunctive pimavanserin in patients with schizophrenia who received stable antipsychotic treatment included measures to encourage and assess treatment adherence.
Objective
This post hoc analysis evaluated adherence levels achieved in the Phase III ENHANCE study (NCT02970292) and the Phase II ADVANCE study (NCT02970305).
Methods
Blood levels of participants receiving adjunctive treatment with pimavanserin or placebo added to their ongoing antipsychotic medication were tested and evaluated regularly throughout both studies. For both the background antipsychotic and pimavanserin, treatment adherence was defined as a blood sample test result above the lower limit of quantification.
Results
Overall, 392 of 633 screened patients and 403 of 608 screened patients were in the safety populations in ENHANCE and ADVANCE, respectively. In ENHANCE, at weeks 1, 3, and 6/early termination (ET), the adherence rates remained ≥ 95.1% for the background antipsychotic in both pimavanserin and placebo treatment groups and ≥ 96.8% for pimavanserin. In ADVANCE, high adherence rates (≥90.6%) with the background antipsychotic (for both treatment groups) and pimavanserin (≥95.0%) were observed at weeks 2, 8, 14, and 26/ET.
Conclusion
Rigorous screening was performed to exclude patients not adherent to their background antipsychotic before enrollment and to pimavanserin during study visits by using regular blood sampling. Mandatory caregiver participation further supported adherence to study treatment and procedures. These efforts may have contributed to the high levels of adherence to both background antipsychotic and pimavanserin reported in ENHANCE and ADVANCE.
Key Points
Because patients with schizophrenia are known to be nonadherent to their treatment plans, it can be difficult to discern whether poor outcomes are due to the treatment not working or to the patient’s low adherence to their regimen.
For this reason, clinical studies with schizophrenia patients can be difficult and should be optimized for adherence, and measurement of adherence is necessary for interpreting results.
In this study, we analyzed the adherence of schizophrenia patients taking a current antipsychotic in 2 completed clinical trials to show that high levels of treatment adherence are achievable for this patient population.
Data Sharing Statement
The research data collected for this ongoing phase III study on negative symptoms of schizophrenia, including individual participant data, will not be made available on request at this time because it is anticipated that these data may be part of future regulatory submissions.
Acknowledgments
Medical writing and editorial support, under the direction of the authors, were provided by Ashfield MedComms, an Ashfield Health company, and Nathan Hutcheson PhD (Citrus Health Group), in accordance with Good Publication Practices 2022 (GPP 2022).
Author Contributions
Dragana Bugarski-Kirola and Brandon Abbs contributed to the conception and design of the analysis. Dragana Bugarski-Kirola, Brandon Abbs, and Ramzey Odetalla performed data collection; Mona Darwish, Brandon Abbs, and I-Yuan Liu conducted analyses. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
Dragana Bugarski-Kirola, Mona Darwish, and I-Yuan Liu are employees of and stockholders in Acadia Pharmaceuticals Inc. Brandon Abbs, Daryl DeKarske, and Ramzey Odetalla are former employees of Acadia Pharmaceuticals Inc. The authors report no other conflicts of interest in this work.