A Phase 3, Randomized, Double-Blind, Placebo-Controlled Relapse Prevention Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease
This is a Phase 3, 38-week, randomized, double-blind, placebo-controlled, multicenter, outpatient study in subjects with psychosis associated with Alzheimer's Disease. The primary objective of the study is to evaluate relapse prevention in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo. The secondary objectives of the study are to evaluate the time from randomization to discontinuation for any reason or relapse and safety and tolerability in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo.
• Is aged 55 to 90 years, inclusive, at Screening
• Can understand the nature of the study and protocol requirements and provide a signed informed consent form before any study assessments are performed. If the subject is deemed not competent to provide consent, the following requirements for consent 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 of dementia to rule out other central nervous system (CNS) disease that could account for the dementia syndrome. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening.
• Living at the same location for a minimum of 4 weeks before Screening, with the intention of living at the same location throughout the study.
• Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified caregiver or study partner who, in the investigator's judgment, has frequent and sufficient contact with the participant (ie, ≥10 hours per week) on a regular basis to reliably provide accurate information regarding the participant's cognitive, behavioral, and functional status, and is willing to:
• i) Attend all visits and report on participant's status. ii) Oversee participant compliance with medication and study procedures; iii) Participate in the study assessments 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) at Screening and Baseline. CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include hallucinations and delusions.
• Subjects are required to meet at least one of the following criteria at Screening and 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 to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on two of 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 have been on a stable dose for 6 weeks prior to Screening and be willing to maintain a stable dose for the duration of the study.
• Subject is willing and able to visit the clinic in an outpatient setting for the study 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 childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP or matching placebo.