Introduction
diarrhea, salivary hypersecretion, excessive sweating, psychotic disorders, schizophrenia, neuropsychiatric disorders, nausea, vomiting
SALIVARY HYPERSECRETION, PATHOPHYSIOLOGY
Numerous lines of investigation have implicated muscarinic cholinergic systems in the pathophysiology of psychotic disorders and led to targeting muscarinic acetylcholine receptors for innovative therapeutics for these illnesses (Felder et al. KarXT combines xanomeline with trospium, a pan-muscarinic receptor antagonist that is restricted to the periphery (Staskin et al. We present the results of a phase 1 healthy volunteer study (NCT02831231) that was designed to test the ability of trospium to mitigate xanomeline-related cholinergic AEs. The rates of five prespecified cholinergic AEs (nausea, vomiting, diarrhea, excessive sweating, and salivary hypersecretion) were compared between xanomeline plus trospium and xanomeline alone. In addition, vital signs, electrocardiograms (ECGs), and safety laboratory values were assessed, and a self-administered visual analog scale (VAS) and clinician-administered scales were employed. Also, a pharmacokinetic (PK) analysis of xanomeline was conducted to determine if the addition of trospium affected xanomeline blood levels. This trial paved the way for future studies of KarXT in patients with schizophrenia and other neuropsychiatric disorders.