A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1)

Inclusion Criteria:

• Is aged 55 to 90 years, inclusive, at Screening

• Can understand the nature of the study and protocol requirements and provide asigned informed consent form before any study assessments are performed. If thesubject is deemed not competent to provide consent, the following requirements forconsent must be met. i) The subject's legally acceptable representative must provide informed consent;ii) The subject must provide informed consent.

• Meets clinical criteria for possible or probable Alzheimer's Disease

• Has a Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset ofdementia to rule out other central nervous system (CNS) disease that could accountfor the dementia syndrome. If not available, a non-contrast brain MRI ornon-contrast head CT must be done during screening.

• Living at the same location for a minimum of 4 weeks before Screening, with theintention of living at the same location throughout the study.

• Capable of self-locomotion (alone or with the aid of an assistive device) and havean identified caregiver or study partner who, in the investigator's judgment, hasfrequent and sufficient contact with the participant (ie, ≥10 hours per week) on aregular basis to reliably provide accurate information regarding the participant'scognitive, behavioral, and functional status, and is willing to: i) Attend all visits and report on participant's status. ii) Oversee participantcompliance with medication and study procedures; iii) Participate in the studyassessments and provide informed consent to participate in the study.

• History of psychotic symptoms (meeting International Psychogeriatric Association [IPA] criteria) for at least 2 months prior to Screening.

• Clinical Global Impressions-Severity (CGI-S) scale with a score ≥4 (moderate) atScreening and Baseline. CGI-S requires the assessor to consider aspects of thepsychosis prior to providing a global assessment of severity. These aspects includehallucinations and delusions.

• Subjects are required to meet at least one of the following criteria at Screeningand Baseline: i) Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR; ii) Moderate tosevere hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on twoof the seven items.

• Mini-Mental State Examination (MMSE) score of 6 to 24, inclusive, at Screening

• If the subject is taking a cholinesterase inhibitor and/or memantine, they must havebeen on a stable dose for 6 weeks prior to Screening and be willing to maintain astable dose for the duration of the study.

• Subject is willing and able to visit the clinic in an outpatient setting for thestudy duration, follow instructions, and comply with the protocol requirements

• BMI must be within 16 to 40 kg/m2 inclusive

• Female subjects must not be pregnant or breastfeeding. Women of childbearingpotential (WOCBP), or men whose sexual partners are WOCBP, must be able and willingto use at least 1 highly effective method of contraception during the study and forat least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP or matchingplacebo.

Exclusion Criteria:

• Psychotic symptoms that are primarily attributable to a condition other than theAlzheimer's Disease causing dementia

• History of major depressive episode with psychotic features during the 12 monthsprior to Screening

• History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffectivedisorder

• Significant or severe medical conditions including pulmonary, hepatic, renal,hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic,cardiovascular or oncologic disease, or any other condition that, in the opinion ofthe Investigator, could jeopardize the safety of the subject, ability to complete orcomply with the study procedures or validity of the study results

• Significant or severe renal impairment based on a screening cutoff for EstimatedGlomerular Filtration Rate (eGFR) of <50 mL/min

• History of ischemic stroke within 12 months prior to Screening or any evidence ofhemorrhagic stroke

• History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm,unstable thyroid function, or unexplained syncope

• Any of the following: i) New York Heart Association Class 2 congestive heart failure; ii) Grade 2 orgreater angina pectoris; iii) Sustained ventricular tachycardia; iv) Ventricularfibrillation; v) Torsade de pointes; vi) Implantable cardiac defibrillator.

• Myocardial infarction within the 6 months prior to Screening

• Personal or family history of symptoms of long QT syndrome as evaluated by theinvestigator

• Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, active biliarydisease, hepatobiliary carcinoma, and/or active hepatic viral infections asindicated by medical history or liver function tests results

• History or high risk of urinary retention, gastric retention, or narrow-angleglaucoma as evaluated by the investigator

• Participants with any of the following: i) History of bladder stones; ii) History of recurrent urinary tract infections;iii) For male participants:

1. Serum prostate specific antigen (PSA) > 10 ng/mL at Screening

2. An IPSS of 5 (almost always) on items 1, 3, 5, or 6

3. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9

• History of obstructive gastrointestinal disorder, gastric retention, irritable bowelsyndrome (with or without constipation) or serious constipation requiring treatmentwithin the last 6 months

• Risk of suicidal behavior during the study as determined by clinical assessment and/or C-SSRS

• Clinically significant abnormal finding on the physical examination,electrocardiogram, or clinical laboratory results at Screening

• Urine toxicology screen is positive substances other than cannabis orbenzodiazepines (both cannabis and short-or medium-acting benzodiazepines areallowed in limited quantities during the study) unless approval has been given bythe Medical Monitor

• Currently receiving monoamine oxidase inhibitors, anticonvulsants (e.g.,lamotrigine, divalproex), mood stabilizers (eg, lithium) tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except foras-needed anxiolytics (e.g., lorazepam) and unable to complete the washout: i) Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptakeinhibitors taken at a stable dose for at least 8 weeks prior to Screening may bepermitted; ii) Mirtazapine or trazodone may be used if started at least 8 weeksprior to Screening. If needed, an extension (up to two weeks) of the ScreeningPeriod may be allowed with approval of the Sponsor/Medical Monitor.

• If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject isunsuitable for enrollment in the study or subject has any finding that, in the viewof the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety ofthe subject or affect his/her ability to adhere to the protocol visit schedule orfulfill visit requirements

• Positive test for coronavirus (COVID-19) within 2 weeks before or at Screening;antigen or PCR local testing can be done at the discretion of the Investigator

• Unable to taper and discontinue a concomitant medication that would precludeparticipation in the study

• Prior exposure to KarXT

• Experienced any significant adverse events due to trospium, including a knownhypersensitivity to trospium

• Participation in another clinical study in which the subject received anexperimental or investigational drug within 3 months before Screening or hasparticipated in more than 2 clinical studies in the past year

• Other protocol-defined Inclusion/Exclusion criteria apply