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

Inclusion Criteria:

1. Is aged 55 to 90 years, inclusive, at Screening

2. 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.

3. The subject's legally acceptable representative or caregiver/study partner, iflocal regulations allow, must provide informed consent

4. The subject must provide informed assent

5. Meets clinical criteria for possible or probable Alzheimer's Disease

6. 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.

7. Living at the same home or residential assisted-living facility for a minimum of sixweeks before Screening

8. Capable of self-locomotion (alone or with the aid of an assistive device) and havean identified or proxy caregiver (spends approximately 10 hours/week with thesubject) that is willing to:

9. Attend all visits and report on subject's status

10. Oversee subject compliance with medication and study procedures

11. Participate in the study assessments and provide informed consent toparticipate in the study

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

13. 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.

14. Subjects are required to meet at least one of the following criteria at Screeningand Baseline:

15. Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR

16. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domainscore of ≥ 2 on two of the seven items.

17. Mini-Mental State Examination (MMSE) score of 8 to 22, inclusive, at Screening

18. 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.

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

20. BMI must be within 18 to 40 kg/m2 inclusive

21. 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. Sperm donation is not allowed for 30 days after the final dose of the IMPor matching placebo.

Exclusion Criteria:

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

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

3. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffectivedisorder

4. 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

5. Significant or severe renal impairment based on a screening cutoff for EstimatedGlomerular Filtration Rate (eGFR) of <60 mL/min/1.73 m2

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

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

8. Any of the following:

9. New York Heart Association Class 2 congestive heart failure

10. Grade 2 or greater angina pectoris

11. Sustained ventricular tachycardia

12. Ventricular fibrillation

13. Torsade de pointes

14. Implantable cardiac defibrillator

15. Myocardial infarction within the 6 months prior to Screening

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

17. Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, hepatobiliarycarcinoma, and/or active hepatic viral infections as indicated by medical history orliver function tests results

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

19. For males only, any one of the following:

20. History of bladder stones

21. History of recurrent urinary tract infections

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

23. An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1, 3, 5, or 6

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

25. History of irritable bowel syndrome (with or without constipation) or seriousconstipation requiring treatment within the last 6 months

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

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

28. 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

29. Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (e.g.,lamotrigine, divalproex), lithium, tricyclic antidepressants (e.g., imipramine,desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate)

30. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptakeinhibitors taken at a stable dose for at least 8 weeks prior to Screening maybe permitted

31. Mirtazapine or trazodone may be used as a hypnotic 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.

32. 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

33. 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

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

35. Prior exposure to KarXT

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

37. 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