TABLE 1.

Details of various clinical trials of xanomeline + trospium (KarXT).^21–30

CLINICAL TRIAL IDENTIFIER	PRIMARY ENDPOINT(S)	INTERVENTION	PHASE	NUMBER OF PARTICIPANTS	RANDOMIZED/MASKING	STATUS
NCT02831231	Mean weekly maximum composite Visual Analogue Scale (VAS) score (nausea, diarrhea, sweating, salivation, and vomiting combined)	xanomeline 75mg thrice daily and trospium 20mg twice daily xanomeline 75mg thrice daily and placebo twice daily	I	70	RDBPCT	Completed
Brannan S et al (2018)	Incidence of cholinergic adverse events of nausea, vomiting, diarrhea, excessive sweating, and salivation.	xanomeline 100mg twice daily and trospium 20mg twice daily xanomeline 125mg twice daily and trospium 40mg twice daily xanomeline 150mg twice daily and trospium 20mg twice daily	I	69	RDBPCT	Completed
NCT03697252 (EMERGENT-1) (KAR-004)	CFB in PANSS Total score at Week 5	xanomeline 125mg and trospium 30mg twice daily vs. placebo (variable dosing schedule)*	II	182	RDBPCT	Completed
NCT04659161 (EMERGENT-2)	CFB in PANSS Total score at Week 5	xanomeline 125mg and trospium 30mg twice daily vs. placebo (variable dosing schedule)*	III	246	RDBPCT	Recruiting
NCT04738123 (EMERGENT-3)	CFB in PANSS Total score at Week 5	xanomeline 125mg and trospium 30mg twice daily vs. placebo (variable dosing schedule)*	III	246	RDBPCT	Recruiting
NCT04659174 (EMERGENT-4)	Incidence of TEAEs up to 53 weeks	xanomeline 125mg and trospium 30mg twice daily vs. placebo (variable dosing schedule)**	III	350	Open-label	Recruiting
NCT04820309 (EMERGENT-5)	Incidence of TEAEs up to 53 weeks	xanomeline 125mg and trospium 30mg twice daily vs. placebo (variable dosing schedule)**	III	400	Open-label	Recruiting
NCT05145413	CFB in PANSS Total score at Week 6	xanomeline 50mg and trospium 20mg twice daily xanomeline 75mg and trospium 20mg twice daily xanomeline 100mg and trospium 20mg twice daily xanomeline 125mg and trospium 30mg twice daily vs. placebo	III	400	RDBPCT	Recruiting

^*Variable dosing schedule of xanomeline 50mg and trospium 20mg on Days 1 and 2, followed by xanomeline 100mg and trospium 20mg for Days 3–7, then xanomeline 125mg and trospium 30mg for Days 8–35. If the patient was not able to tolerate the highest dose, there was an option to return to xanomeline 100mg and trospium 20mg.

^**Variable dosing schedule of xanomeline 50mg and trospium 20mg on Days 1 and 2, followed by xanomeline 100mg and trospium 20mg for days 3–7, then xanomeline 125mg and trospium 30mg for Days 8–364. If the patient was not able to tolerate the highest dose, there was an option of returning to xanomeline 100mg and trospium 20mg.

CFB: Change from baseline; PANSS: Positive and Negative Syndrome Scale; RDBPCT: randomized, double-blind, placebo-controlled trial; TEAE: treatment-emergent adverse event