THE SAFETY AND TOLERANCE OF XANOMELINE TARTRATE IN PATIENTS WITH ALZHEIMERS-DISEASE

Xonomeline tartrate (active ingredient xanomeline) is a muscarinic ago nist that has demonstrated specificity for the M(1) receptor in precli nical studies and has been well tolerated at dosages up to 50 mg three times a day in healthy elderly subjects. To define the maximum tolera ted dose (MTD) of xanomeline tartrate in patients with Alzheimer's dis ease, 48 patients (20 men, 28 women) with probable Alzheimer's disease were enrolled in a double-blind, placebo-controlled inpatient study t o determine the safety and tolerability of 8 fixed dosages of xanomeli ne tartrate (25, 35, 50, 60, 75, 90, 100, and 115 mg, all three times a day) given for 7 days. For each dosage the treatment panel consisted of six patients (four taking xanomeline tartrate and two taking place bo). With the discontinuation of two patients because of severe intole rable adverse events, a minimum intolerated dose was reached at 115 mg three times a day, and 100 mg three times a day was defined as the MT D. This MTD in patients was two-fold greater than the MTD previously d etermined in healthy elderly volunteers.