Poster
77
(#77) Safety and Efficacy of Adjunctive Xanomeline and Trospium Chloride in People With Inadequately Controlled Schizophrenia Symptoms in the ARISE Trial
Psych Congress 2025
Abstract: Background: Xanomeline/trospium chloride (X/T) is the first approved schizophrenia treatment with no direct D2 dopamine receptor binding activity. Given its unique and complementary MOA to antipsychotics (APDs), adjunctive X/T may benefit people with inadequately controlled schizophrenia symptoms.
Methods: ARISE (NCT05145413) was a randomized, double-blind, placebo-controlled trial in adults with inadequately controlled schizophrenia symptoms on a stable dose of APD monotherapy. Participants were randomized 1:1 to adjunctive X/T (titrated to maximum of 125mg/30mg) or placebo for 6 weeks. Primary endpoint was change from baseline (CFB) to week 6 in PANSS total score. Secondary endpoints included CFB to week 6 in PSP and CGI-S scores. Safety assessments included TEAEs.
Results: 396 participants were randomized (X/T+APD: n=197; placebo+APD: n=199). In the mITT population (X/T+APD: n=190; placebo+APD: n=196), LSM CFB to week 6 in PANSS total score numerically favored X/T+APD vs placebo+APD (mean±SE: -14.3±1.01 vs -12.2±0.98; P=0.11; LSM±SE difference: -2.00±1.27) but was not statistically significant. No meaningful between-group differences were observed for PSP and CGI-S scores. In a post hoc analysis, greater CFB in PANSS positive subscale with X/T+APD versus placebo+APD was clinically meaningful (LSM [95%CI] difference: -1.00 [-1.9, -0.2]). Consistent with the monotherapy trials, the most common TEAEs were nausea (16% vs 3%), vomiting (11% vs 2%), and dry mouth (9% vs 2%); most were mild or moderate.
Conclusion: Adjunctive X/T showed numerical but not statistically significant improvements in schizophrenia symptoms in those with inadequately controlled symptoms receiving APD. The safety and tolerability profile of adjunctive X/T was consistent with previous monotherapy trials.
Short Description: The phase 3, randomized, double-blind, placebo-controlled ARISE trial evaluated adjunctive xanomeline/trospium in adults with schizophrenia inadequately controlled on antipsychotic therapy. At week 6, xanomeline/trospium showed numerical but not statistically significant improvement in PANSS total score vs placebo. No differences were observed in PSP or CGI-S scores. The most common treatment-emergent adverse events were nausea, vomiting, and dry mouth. The safety and tolerability profile of xanomeline/trospium as an adjunctive treatment was consistent with previous monotherapy trials.
Name of Sponsoring Organization(s): Bristol Myers Squibb
Methods: ARISE (NCT05145413) was a randomized, double-blind, placebo-controlled trial in adults with inadequately controlled schizophrenia symptoms on a stable dose of APD monotherapy. Participants were randomized 1:1 to adjunctive X/T (titrated to maximum of 125mg/30mg) or placebo for 6 weeks. Primary endpoint was change from baseline (CFB) to week 6 in PANSS total score. Secondary endpoints included CFB to week 6 in PSP and CGI-S scores. Safety assessments included TEAEs.
Results: 396 participants were randomized (X/T+APD: n=197; placebo+APD: n=199). In the mITT population (X/T+APD: n=190; placebo+APD: n=196), LSM CFB to week 6 in PANSS total score numerically favored X/T+APD vs placebo+APD (mean±SE: -14.3±1.01 vs -12.2±0.98; P=0.11; LSM±SE difference: -2.00±1.27) but was not statistically significant. No meaningful between-group differences were observed for PSP and CGI-S scores. In a post hoc analysis, greater CFB in PANSS positive subscale with X/T+APD versus placebo+APD was clinically meaningful (LSM [95%CI] difference: -1.00 [-1.9, -0.2]). Consistent with the monotherapy trials, the most common TEAEs were nausea (16% vs 3%), vomiting (11% vs 2%), and dry mouth (9% vs 2%); most were mild or moderate.
Conclusion: Adjunctive X/T showed numerical but not statistically significant improvements in schizophrenia symptoms in those with inadequately controlled symptoms receiving APD. The safety and tolerability profile of adjunctive X/T was consistent with previous monotherapy trials.
Short Description: The phase 3, randomized, double-blind, placebo-controlled ARISE trial evaluated adjunctive xanomeline/trospium in adults with schizophrenia inadequately controlled on antipsychotic therapy. At week 6, xanomeline/trospium showed numerical but not statistically significant improvement in PANSS total score vs placebo. No differences were observed in PSP or CGI-S scores. The most common treatment-emergent adverse events were nausea, vomiting, and dry mouth. The safety and tolerability profile of xanomeline/trospium as an adjunctive treatment was consistent with previous monotherapy trials.
Name of Sponsoring Organization(s): Bristol Myers Squibb
