週1回服用可能な統合型精神科薬カプセルの臨床試験成功(Weekly pill for schizophrenia shows promise in clinical trials)

2025-06-10 マサチューセッツ工科大学(MIT)

The ingestible capsule is about the size of a multivitamin, and once swallowed, it expands into a star shape that helps it remain in the stomach until all of the drug is released.　Credit: Adam Glanzman

<関連情報>

• https://news.mit.edu/2025/weekly-pill-schizophrenia-shows-promise-clinical-trials-0610
• https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00135-X/abstract

米国における統合失調症に対する長時間作用型経口リスペリドン(LYN-005)の週1回投与(STARLYNG-1):多施設非盲検非ランダム化第3相試験 Long-acting oral weekly risperidone (LYN-005) for schizophrenia in the USA (STARLYNG-1): a multicentre, open-label, non-randomised phase 3 trial

Leslie Citrome, MD ∙ Nayana Nagaraj, MD ∙ Giovanni Traverso, MD ∙ Todd Dumas, PharmD ∙ Richard Scranton, MD
The Lancet Psychiatry  Published: July 2025
DOI:https://doi.org/10.1016/S2215-0366(25)00135-X

Summary

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 [C_min] at weeks 1 and 5, and maximum concentration [C_max] and average concentration [C_avg] 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 C_min at week 1 and week 5 (90% CI ≥0·8), C_max at week 5 (90% CI ≤1·25), and C_avg 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 C_min 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 C_min, C_max, and C_avg, 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.