Targeting muscarinic receptors in schizophrenia treatment: Novel antipsychotic xanomeline/trospium chloride

Table 2 Key findings on the effects based on the positive and negative syndrome scale scores from completed 5-week clinical trials

Variable	EMERGENT-1[43]		EMERGENT-2[14]		EMERGENT-3[47]
	KarXT vs placebo	P value	KarXT vs placebo	P value	KarXT vs placebo	P value
Number of patients (modified intention-to-treat population)	83 vs 87	-	117 vs 119	-	114 vs 120	-
Least-squares mean change from baseline in PANSS total score (points)	-17.4 vs -5.9	< 0.001	-21.2 vs -11.6	< 0.0001	-20.6 vs -12.2	< 0.0001
Least-squares mean change from baseline in PANSS positive symptom subscore (points)	-5.6 vs -2.4	< 0.001	-6.8 vs -3.9	< 0.0001	-7.1 vs -3.6	< 0.0001
Least-squares mean change from baseline in PANSS negative symptom subscore (points)	-3.2 vs -0.9	< 0.001	-3.4 vs -1.6	0.0055	-2.7 vs -1.8	0.1224
Least-squares mean change from baseline in PANSS Marder negative symptom subscore (points)	-3.9 vs -1.3	< 0.001	-4.2 vs -2.0	0.0022	-3.5 vs -2.7	0.1957

Studies included patients aged 18-60 years (EMERGENT-1) or up to 65 years (EMERGENT-2 and EMERGENT-3) with a primary diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition, experiencing an acute exacerbation or relapse of psychosis requiring hospitalization with onset within 2 months before screening. Participants were required to be free of antipsychotic medication for a specified period before the baseline assessment: In EMERGENT-1, at least two weeks for oral antipsychotics or 1.5 injection cycles for long-acting injectables (LAI); and in EMERGENT-2 and EMERGENT-3, at least five half-lives or one week (whichever was longer) for oral antipsychotics, or at least 12 weeks for LAI (24 weeks for paliperidone palmitate). KarXT: Xanomeline/trospium chloride; PANSS: Positive and Negative Syndrome Scale.