:
1. Psychotic symptoms that are primarily attributable to a condition other than the
Alzheimer's Disease causing dementia
2. History of major depressive episode with psychotic features during the 12 months
prior to Screening
3. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective
disorder
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 of
the Investigator, could jeopardize the safety of the subject, ability to complete or
comply with the study procedures or validity of the study results
5. Significant or severe renal impairment based on a screening cutoff for Estimated
Glomerular Filtration Rate (eGFR) of <60 mL/min/1.73 m2
6. History of ischemic stroke within 12 months prior to Screening or any evidence of
hemorrhagic stroke
7. History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm,
unstable thyroid function, or unexplained syncope
8. Any of the following:
1. New York Heart Association Class 2 congestive heart failure
2. Grade 2 or greater angina pectoris
3. Sustained ventricular tachycardia
4. Ventricular fibrillation
5. Torsade de pointes
6. Implantable cardiac defibrillator
9. Myocardial infarction within the 6 months prior to Screening
10. Personal or family history of symptoms of long QT syndrome as evaluated by the
investigator
11. Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, hepatobiliary
carcinoma, and/or active hepatic viral infections as indicated by medical history or
liver function tests results
12. History or high risk of urinary retention, gastric retention, or narrow-angle
glaucoma as evaluated by the investigator
13. For males only, any one of the following:
1. History of bladder stones
2. History of recurrent urinary tract infections
3. Serum prostate specific antigen (PSA) > 10 ng/mL at Screening
4. An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1,
3, 5, or 6
5. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9
14. History of irritable bowel syndrome (with or without constipation) or serious
constipation requiring treatment within the last 6 months
15. Risk of suicidal behavior during the study as determined by clinical assessment and/
or C-SSRS
16. Clinically significant abnormal finding on the physical examination,
electrocardiogram, or clinical laboratory results at Screening
17. Urine toxicology screen is positive substances other than cannabis or
benzodiazepines (both cannabis and short-or medium-acting benzodiazepines are
allowed in limited quantities during the study) unless approval has been given by
the Medical Monitor
18. 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)
1. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake
inhibitors taken at a stable dose for at least 8 weeks prior to Screening may
be permitted
2. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks
prior to Screening. If needed, an extension (up to two weeks) of the Screening
Period may be allowed with approval of the Sponsor/Medical Monitor.
19. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is
unsuitable for enrollment in the study or subject has any finding that, in the view
of the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety of
the subject or affect his/her ability to adhere to the protocol visit schedule or
fulfill visit requirements
20. 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
21. Unable to taper and discontinue a concomitant medication that would preclude
participation in the study
22. Prior exposure to KarXT
23. Experienced any significant adverse events due to trospium, including a known
hypersensitivity to trospium
24. Participation in another clinical study in which the subject received an
experimental or investigational drug within 3 months before Screening or has
participated in more than 2 clinical studies in the past year
Recruiting
