NYMC Faculty Publications

Long-Acting Oral Weekly Risperidone (LYN-005) for Schizophrenia in the USA (STARLYNG-1): A Multicentre, Open-Label, Non-Randomised Phase 3 Trial

Author Type(s)

Faculty

DOI

10.1016/S2215-0366(25)00135-X

Journal Title

Lancet Psychiatry

First Page

504

Last Page

512

Document Type

Article

Publication Date

7-1-2025

Department

Psychiatry and Behavioral Sciences

Disciplines

Medicine and Health Sciences

Abstract

Background: Medication non-adherence and insufficiently managed disease worsen outcomes in people with schizophrenia. We aimed to compare the bioavailability of a long-acting oral weekly formulation of risperidone, LYN-005, with daily oral risperidone at steady state. Methods: In this open-label, non-randomised, phase 3 trial, clinically stable participants with schizophrenia or schizoaffective disorder were enrolled from five sites across the USA while residing in an inpatient facility for 5 weeks (with the exception of days 9–13). After a 7-day run-in period with immediate-release risperidone (2 mg or 6 mg), participants received five doses of long-acting oral weekly LYN-005 (15 mg or 45 mg, respectively), with a supplemental half dose of daily immediate-release risperidone during week 1. Primary endpoints compared pharmacokinetic parameters of LYN-005 (minimum concentration [Cmin] at weeks 1 and 5, and maximum concentration [Cmax] and average concentration [Cavg] at week 5) with those of immediate-release risperidone on the last day of the run-in period. Prespecified primary endpoint criteria were geometric mean ratios for Cmin at week 1 and week 5 (90% CI ≥0·8), Cmax at week 5 (90% CI ≤1·25), and Cavg at week 5 (0·8 ≤90% CI ≤1·4). No people with lived experience were involved in the study design. This study was registered with ClinicalTrials.gov, NCT05779241, and has been completed. Findings: Between April 13, 2023 and Dec 1, 2023, 83 participants were enrolled in the study (62 [75%] male and 21 [25%] female; 67 [81%] Black or African American, mean age 49·3 years [SD 11·5]), of whom 47 participants completed the 5-week study. In the pharmacokinetic analysis (n=44), sustained release of the active moiety was observed across all doses of LYN-005. Geometric mean ratios of LYN-005 versus immediate-release risperidone were 1·02 (90% CI 0·93–1·12) for Cmin at week 1, and 1·04 (90% CI 0·87–1·23), 0·84 (0·77–0·92), and 1·03 (0·93–1·13) for Cmin, Cmax, and Cavg, respectively, at week 5 and met predetermined criteria. In individuals taking LYN-005 (n=67), gastrointestinal treatment-emergent adverse events were most common (44 [66%] participants), with one serious treatment-emergent adverse event reported. Interpretation: Weekly LYN-005 provided sustained release of risperidone at therapeutic concentrations with similar bioavailability to immediate-release risperidone. Patients remained clinically stable and no unexpected safety signals emerged. This offers a novel long-acting oral drug delivery technology for schizophrenia and schizoaffective disorder. Funding: Lyndra Therapeutics.

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