Psychosis Associated With Alzheimer's Disease
Conditions
Brief summary
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of KarXT in male and female subjects who are aged 55 to 90 years and have mild to severe Alzheimer's Disease (AD) with moderate to severe psychosis related to AD. The primary objective of the study is to evaluate the efficacy of KarXT compared with placebo in the treatment of subjects with psychosis associated with AD as measured by the Neuropsychiatric Inventory-Clinician (NPI-C): Hallucinations and Delusions (H+D) score.
Interventions
DRUGKarXT
KarXT 20/2 mg (total daily dose \[TDD\] 60/6 mg) KarXT 30/3 mg (TDD 90/9 mg) KarXT 40/4 mg (TDD 120/12 mg) KarXT 50/5 mg (TDD 150/15 mg) KarXT 66.7/6.67 mg (TDD 200/20 mg)
DRUGPlacebo
Placebo capsules
Sponsors
Karuna Therapeutics, Inc., a Bristol Myers Squibb company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Is a male or female aged 55 to 90 years, inclusive, at Screening. 2. Can understand the nature of the trial and protocol requirements and provide informed consent or assent before any study assessments are performed. 3. Meets clinical criteria for Possible AD or Probable AD. 4. 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. 5. Living at the same home or residential assisted-living facility for a minimum of 6 weeks before Screening. 6. Have an identified study partner who should have daily contact (approximately 10 hours a week or more). 7. History of psychotic symptoms (meeting International Psychogeriatric Association criteria) (Cummings 2020) for at least 2 months prior to Screening. 8. CGI-S scale with a score ≥ 4 at Screening and Baseline. 9. 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: 1. Moderate to severe delusions, defined as NPI-C: Delusions domain score of ≥ 2 on 2 of the 8 items OR 2. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on 2 of the 7 items 10. MMSE score of 8 to 22, inclusive, at Screening. Key
Exclusion criteria
1. Psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia. 2. History of major depressive episode with psychotic features during the 12 months prior to Screening. 3. History 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. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator. 6. Prior exposure to KarXT. 7. History of hypersensitivity to KarXT excipients or trospium chloride. 8. Experienced any significant adverse events (AEs) due to trospium. 9. 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. 10. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to End of Treatment in the Neuropsychiatric Inventory-Clinician: Hallucinations and Delusions (NPI-C: H+D) score | Baseline and end of Treatment (up to 14 Weeks) | Neuropsychiatric Inventory-Clinician: Hallucinations and Delusions scale includes 2 domains from the NPI-C scale, namely, hallucinations and delusions. These 2 domains include the following number of items to be rated by the clinician: Hallucinations, 7 items (maximum score = 21) and Delusions, 8 items (maximum score = 24). The maximum score for the NPI-C: H+D scale is 45. Higher scores on this scale indicate worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to End of Treatment in the Clinical Global Impressions-Severity (CGI-S) scale | Baseline and end of Treatment (up to 14 Weeks) | Clinical Global Impressions-Severity (CGI-S) requires the assessor to consider aspects of the psychosis (hallucinations and delusions) prior to providing a global assessment of severity. Higher scores on this scale indicate worse outcomes. |
| Change From Baseline to end of Treatment in NPI-C Core score: Hallucinations, Delusions, Agitation, and Aggression Domains | Baseline and end of Treatment (up to 14 Weeks) | — |
| Change From Baseline to end of Treatment in NPI-C: Agitation score | Baseline and end of Treatment (up to 14 Weeks) | — |
| Change From Baseline to end of Treatment in NPI-C Core score: Caregiver Distress scale (Hallucinations, Delusions, Agitation, and Aggression domains) | Baseline and end of Treatment (up to 14 Weeks) | — |
| Responder Rate | Baseline and end of Treatment (up to 14 Weeks) | Responder rate is defined as NPI-C: H+D score ≥ 40% improvement |
Countries
Belgium, Canada, Chile, China, Greece, Hungary, Mexico, Peru, Poland, South Korea, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed