Poster
82
(#82) Long-Term Safety and Tolerability of Xanomeline and Trospium Chloride: Pooled Results From the 52-Week, Open-Label EMERGENT-4 and EMERGENT-5 Trials
Psych Congress 2025
Abstract: Background: Xanomeline/trospium (X/T), which combines the dual M1/M4 muscarinic agonist xanomeline with the peripherally restricted pan-muscarinic receptor antagonist trospium chloride, is approved by the U.S. FDA for treatment of schizophrenia in adults. X/T was well tolerated and associated with significant symptom improvement in the 5-week EMERGENT trials. We report a pooled analysis of long-term safety from the 52-week EMERGENT-4 and EMERGENT-5 trials.
Methods: EMERGENT-4 (NCT04659174) was an open-label extension of EMERGENT-2/3 (NCT04659161/NCT04738123), which enrolled participants with schizophrenia experiencing worsening psychosis symptoms requiring hospitalization. EMERGENT-5 (NCT04820309) enrolled participants with stable schizophrenia symptoms and no prior X/T exposure. All participants received twice-daily X/T chloride 50 mg/20 mg and titrated up to 125 mg/30 mg for 52 weeks. Adverse events (AEs) were monitored throughout. The pooled safety population included participants receiving ≥1 X/T dose in EMERGENT-4/5.
Results: X/T was well tolerated in the safety population (N=718), with no new safety issues. 549 (76.5%) participants reported ≥1 treatment-emergent AE (TEAE). TEAEs/treatment-related TEAEs reported by ≥5% of participants were nausea (20.2%/18.8%), vomiting (17.8%/15.7%), constipation (15.2%/13.9%), hypertension (9.3%/6.3%), dry mouth (8.5%/8.2%), diarrhea (8.4%/5.8%), dizziness (7.8%/6.7%), dyspepsia (7.5%/6.4%), and somnolence (5.4%/5.0%); headache was a TEAE in 7.2% of participants. The incidences of treatment-related weight decreases (2.5%), weight increases (2.1%), and prolactin increases (0.6%) were low.
Conclusions: Pooled analysis of these long-term, open-label trials found that X/T was generally well tolerated in an outpatient setting. Combined with positive efficacy data from the EMERGENT trials, these results support X/T as a new therapeutic option for people living with schizophrenia.
Short Description: Brief Description: This pooled analysis from the 52-week EMERGENT-4/5 trials evaluated the long-term safety of xanomeline/trospium (X/T) in adults with schizophrenia. X/T was well tolerated in the 718 total participants included in the pooled safety population. 549 (76.5%) participants reported ≥1 treatment-emergent adverse event (TEAE). The most common TEAEs were nausea (20.2%), vomiting (17.8%), and constipation (15.2%). These findings support X/T as a new therapeutic option for adults living with schizophrenia.
Name of Sponsoring Organization(s): Bristol Myers Squibb
Methods: EMERGENT-4 (NCT04659174) was an open-label extension of EMERGENT-2/3 (NCT04659161/NCT04738123), which enrolled participants with schizophrenia experiencing worsening psychosis symptoms requiring hospitalization. EMERGENT-5 (NCT04820309) enrolled participants with stable schizophrenia symptoms and no prior X/T exposure. All participants received twice-daily X/T chloride 50 mg/20 mg and titrated up to 125 mg/30 mg for 52 weeks. Adverse events (AEs) were monitored throughout. The pooled safety population included participants receiving ≥1 X/T dose in EMERGENT-4/5.
Results: X/T was well tolerated in the safety population (N=718), with no new safety issues. 549 (76.5%) participants reported ≥1 treatment-emergent AE (TEAE). TEAEs/treatment-related TEAEs reported by ≥5% of participants were nausea (20.2%/18.8%), vomiting (17.8%/15.7%), constipation (15.2%/13.9%), hypertension (9.3%/6.3%), dry mouth (8.5%/8.2%), diarrhea (8.4%/5.8%), dizziness (7.8%/6.7%), dyspepsia (7.5%/6.4%), and somnolence (5.4%/5.0%); headache was a TEAE in 7.2% of participants. The incidences of treatment-related weight decreases (2.5%), weight increases (2.1%), and prolactin increases (0.6%) were low.
Conclusions: Pooled analysis of these long-term, open-label trials found that X/T was generally well tolerated in an outpatient setting. Combined with positive efficacy data from the EMERGENT trials, these results support X/T as a new therapeutic option for people living with schizophrenia.
Short Description: Brief Description: This pooled analysis from the 52-week EMERGENT-4/5 trials evaluated the long-term safety of xanomeline/trospium (X/T) in adults with schizophrenia. X/T was well tolerated in the 718 total participants included in the pooled safety population. 549 (76.5%) participants reported ≥1 treatment-emergent adverse event (TEAE). The most common TEAEs were nausea (20.2%), vomiting (17.8%), and constipation (15.2%). These findings support X/T as a new therapeutic option for adults living with schizophrenia.
Name of Sponsoring Organization(s): Bristol Myers Squibb
