TY - JOUR
T1 - Antipsychotic Efficacy of KarXT (Xanomeline-Trospium)
T2 - Post Hoc Analysis of Positive and Negative Syndrome Scale Categorical Response Rates, Time Course of Response, and Symptom Domains of Response in a Phase 2 Study
AU - Weiden, Peter J.
AU - Breier, Alan
AU - Kavanagh, Sarah
AU - Miller, Andrew C.
AU - Brannan, Stephen K.
AU - Paul, Steven M.
N1 - Funding Information:
consulting services to Karuna Therapeutics and Perception Neuroscience and holds equity in Karuna Therapeutics. Ms Kavanagh provides consulting services for Karuna Therapeutics, UCB Pharma, Novartis Gene Therapies, Worldwide Clinical Trials, PharPoint Research, and Nesos Inc. Funding/support: This research was sponsored by Karuna Therapeutics and the Wellcome Trust (award 208970/Z/17/Z). Funding for additional statistical support was provided by Karuna Therapeutics. Role of the sponsor: The sponsor was involved in the design and conduct of the study; collection, analysis, and interpretation of data; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication. Previous presentation: Part of the data in this manuscript were previously presented as a poster at the Schizophrenia International Research Society Virtual Congress, April 17−21, 2021 (Poster T54). Acknowledgments: The authors thank the study patients and the investigators for their participation. Medical writing and editorial support were provided by Austin Ulrich, PharmD, and Jeni Crockett-Holme, BA, of Dragonfly Editorial (Tipp City, Ohio) and Shannon Davis, BA, and Matthew Jacobson, MALS, CMPP, of Apollo Medical Communications (Guilford, Connecticut) and funded by Karuna Therapeutics. Mr Jacobson and Ms Davis have no conflicts of interest to disclose. Supplementary material: Available at PSYCHIATRIST.COM.
Publisher Copyright:
© 2022 Physicians Postgraduate Press Inc.. All rights reserved.
PY - 2022/5
Y1 - 2022/5
N2 - Objective: To evaluate Positive and Negative Syndrome Scale (PANSS) categorical response rates, time course of response, and symptom subdomains of response with the combination oral agent KarXT (xanomeline-trospium) in the treatment of schizophrenia. Methods: Post hoc analysis was conducted for EMERGENT-1 (NCT03697252), a 5-week, inpatient, placebo-controlled, phase 2 study of acute psychosis in patients who met DSM-5 criteria for schizophrenia. The EMERGENT-1 study was conducted between September 2018 and August 2019. Categorical thresholds of response used were PANSS total score reductions of ≥ 20%, ≥ 30%, ≥ 40%, and ≥ 50% between baseline and study end. Number needed to treat (NNT) for each categorical threshold was calculated. The proportion of KarXT- and placebotreated patients achieving each response threshold at weeks 2, 4, and 5 was assessed. Marder 5-factor analysis of PANSS assessed response with KarXT across symptom domains. Results: A total of 83 patients in the KarXT group and 87 patients in the placebo group were included in the modified intent-to-treat analysis. Response rates with KarXT ranged from 59.0% for a ≥ 20% threshold to 15.7% for a ≥ 50% threshold. All response rates with KarXT were significantly higher than in the placebo arm (P < .05), with NNTs ranging from 3 (≥ 20% improvement) to 11 (≥ 50% improvement). KarXT was associated with a significantly higher response rate relative to placebo as early as 2 weeks for ≥ 20% (P = .0001) and ≥ 30% (P = .0022) thresholds and at 4 weeks for the ≥ 40% (P = .0049) and ≥ 50% (P = .0041) thresholds. Each of the Marder 5 factors showed significant differences favoring KarXT over placebo (P < .05) by 2 weeks and continuing through week 5 (endpoint Cohen d effect sizes, 0.48-0.66). Conclusions: KarXT provided clinically meaningful responder rates on PANSS total score compared with placebo at each response threshold, providing further support of the successful primary and secondary endpoints. Response was demonstrated as early as 2 weeks relative to placebo. KarXT demonstrated improvements vs placebo in all 5 factors (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility, and anxiety/depression).
AB - Objective: To evaluate Positive and Negative Syndrome Scale (PANSS) categorical response rates, time course of response, and symptom subdomains of response with the combination oral agent KarXT (xanomeline-trospium) in the treatment of schizophrenia. Methods: Post hoc analysis was conducted for EMERGENT-1 (NCT03697252), a 5-week, inpatient, placebo-controlled, phase 2 study of acute psychosis in patients who met DSM-5 criteria for schizophrenia. The EMERGENT-1 study was conducted between September 2018 and August 2019. Categorical thresholds of response used were PANSS total score reductions of ≥ 20%, ≥ 30%, ≥ 40%, and ≥ 50% between baseline and study end. Number needed to treat (NNT) for each categorical threshold was calculated. The proportion of KarXT- and placebotreated patients achieving each response threshold at weeks 2, 4, and 5 was assessed. Marder 5-factor analysis of PANSS assessed response with KarXT across symptom domains. Results: A total of 83 patients in the KarXT group and 87 patients in the placebo group were included in the modified intent-to-treat analysis. Response rates with KarXT ranged from 59.0% for a ≥ 20% threshold to 15.7% for a ≥ 50% threshold. All response rates with KarXT were significantly higher than in the placebo arm (P < .05), with NNTs ranging from 3 (≥ 20% improvement) to 11 (≥ 50% improvement). KarXT was associated with a significantly higher response rate relative to placebo as early as 2 weeks for ≥ 20% (P = .0001) and ≥ 30% (P = .0022) thresholds and at 4 weeks for the ≥ 40% (P = .0049) and ≥ 50% (P = .0041) thresholds. Each of the Marder 5 factors showed significant differences favoring KarXT over placebo (P < .05) by 2 weeks and continuing through week 5 (endpoint Cohen d effect sizes, 0.48-0.66). Conclusions: KarXT provided clinically meaningful responder rates on PANSS total score compared with placebo at each response threshold, providing further support of the successful primary and secondary endpoints. Response was demonstrated as early as 2 weeks relative to placebo. KarXT demonstrated improvements vs placebo in all 5 factors (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility, and anxiety/depression).
UR - http://www.scopus.com/inward/record.url?scp=85135965146&partnerID=8YFLogxK
U2 - 10.4088/JCP.21m14316
DO - 10.4088/JCP.21m14316
M3 - Article
C2 - 35552528
AN - SCOPUS:85135965146
SN - 0160-6689
VL - 83
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 3
ER -