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

• ClinicalTrials.gov Identifier: NCT06126224
• Recruitment Status: Recruiting
• First Posted: November 13, 2023
• Last Update Posted: April 30, 2024
• Sponsor: Karuna Therapeutics
• Information provided by (Responsible Party): Karuna Therapeutics

Tracking Information

• First Submitted Date: November 3, 2023
• First Posted Date: November 13, 2023
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: December 26, 2023
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2023)

Change from Baseline to End of Treatment in the Neuropsychiatric Inventory-Clinician: Hallucinations and Delusions (NPI-C: H+D) score [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 8, 2023)

• Change from Baseline to End of Treatment in the Cohen-Mansfield Agitation Inventory (CMAI) score [ Time Frame: Baseline and End of Treatment (up to 14 weeks) ]
  Cohen-Mansfield Agitation Inventory (CMAI) is a caregiver's rating 29-item questionnaire used to assess the frequency of manifestations of agitated behaviors in older adults. Each item is rated on a 7-point scale ranging from "1 = never" to "7 = several times per hour." Higher scores on this scale indicate worse outcomes.
• Change from Baseline to End of Treatment in the Clinical Global Impressions-Severity (CGI-S) scale [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Psychosis Associated With Alzheimer's Disease

Intervention

• Drug: KarXT
  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)
• Drug: Placebo
  Placebo Capsules

Study Arms

• Experimental: KarXT
  Xanomeline and Trospium Chloride Capsules
  Intervention: Drug: KarXT
• Placebo Comparator: Placebo
  Placebo Capsules
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 8, 2023): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility 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. Living at the same home or residential assisted-living facility for a minimum of 6 weeks before Screening.
5. Have an identified study partner who should have daily contact (approximately 10 hours a week or more).
6. History of psychotic symptoms (meeting International Psychogeriatric Association criteria) (Cummings 2020) for at least 2 months prior to Screening.
7. CGI-S scale with a score ≥ 4 at Screening and Baseline.

8. 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
9. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Karuna Medical Information; 1-888-783-0380; medinfo@karunatx.com

• Listed Location Countries: Chile, Greece, Korea, Republic of, Poland, United States

Administrative Information

• NCT Number: NCT06126224
• Other Study ID Numbers: KAR-032
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Karuna Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Karuna Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ronald Marcus, MD; Karuna Therapeutics, Inc.

• PRS Account: Karuna Therapeutics
• Verification Date: April 2024