A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-2)

Prior treatment

• History of major depressive episode with psychotic features during the 12 months prior to Screening.
• Prior exposure to KarXT.
• 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 12 months prior to Screening.

Other illness

• Psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia.
• History of bipolar disorder, schizophrenia, or schizoaffective disorder.
• 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.
• History of hypersensitivity to KarXT excipients or trospium chloride.

Other

• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator.
• Experienced any significant adverse events (AEs) due to trospium.
• Other protocol-defined inclusion/exclusion criteria may apply.

• Is a male or female aged 55 to 90 years, inclusive, at Screening.
• Can understand the nature of the trial and protocol requirements and provide informed consent or assent before any study assessments are performed.
• Meets clinical criteria for Possible AD or Probable AD.
• Must have 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 of dementia to rule out other central nervous system (CNS) disease that could account for the dementia syndrome, e.g., major stroke, neoplasm, subdural hematoma. If not available, a non-contrast brain MRI or non-contrast head CT must be done during Screening.
• Living at the same home or residential assisted-living facility for a minimum of 6 weeks before Screening.
• Have an identified study partner who should have daily contact (approximately 10 hours a week or more).
• History of psychotic symptoms (meeting International Psychogeriatric Association criteria) (Cummings 2020) for at least 2 months prior to Screening.
• CGI-S scale with a score ≥ 4 at Screening and Baseline.
• AD subjects are required to have NPI-C: Hallucinations and Delusions (H+D) score of ≥ 6 AND meet at least 1 of the following criteria at Screening and Baseline:
  • Moderate to severe delusions, defined as NPI-C: Delusions domain score of ≥ 2 on 2 of the 8 items OR
  • Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on 2 of the 7 items
• MMSE score of 8 to 22, inclusive, at Screening.