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

• Sponsor: Karuna Therapeutics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT06126224
• Collaborator: (none)
• Enrollment: 400
• Locations: 16
• Arms: 2
• Anticipated Duration (Months): 20
• Patients Per Site: 25
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psychosis Associated With Alzheimer's Disease	Drug: KarXT; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Nov 1, 2023
• Anticipated Primary Completion Date: Jul 1, 2025
• Anticipated Study Completion Date: Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KarXT Xanomeline and Trospium Chloride Capsules	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)
Placebo Comparator: Placebo Placebo Capsules	Drug: Placebo; Placebo Capsules

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Change from Baseline to End of Treatment in the Cohen-Mansfield Agitation Inventory (CMAI) score [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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

9. Moderate to severe delusions, defined as NPI-C: Delusions domain score of ≥ 2 on 2 of the 8 items OR

10. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on 2 of the 7 items

11. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Chandler	Arizona	United States	85286
2	Clinical Trial Site	Anaheim	California	United States	92805
3	Clinical Trial Site	Lafayette	California	United States	94549
4	Clinical Trial Site	Sherman Oaks	California	United States	91403
5	Clinical Trial Site	Miami Gardens	Florida	United States	33014
6	Clinical Trial Site	Miami	Florida	United States	33126
7	Clinical Trial Site	Miami	Florida	United States	33133
8	Clinical Trial Site	Miami	Florida	United States	33135
9	Clinical Trial Site	Miami	Florida	United States	33144
10	Clinical Trial Site	Miami	Florida	United States	33155
11	Clinical Trial Site	Miami	Florida	United States	33174
12	Clinical Trial Site	Miami	Florida	United States	33179
13	Clinical Trial Site	Okeechobee	Florida	United States	34972
14	Clinical Trial Site	Orlando	Florida	United States	32807
15	Clinical Trial Site	Tampa	Florida	United States	33629
16	Clinical Trial Site	Cypress	Texas	United States	77429

Sponsors and Collaborators

• Karuna Therapeutics

Investigators

• Study Director: Paul Yeung, MD, MPH, Karuna Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Karuna Therapeutics
• ClinicalTrials.gov Identifier: NCT06126224
• Other Study ID Numbers: KAR-032
• First Posted: Nov 13, 2023
• Last Update Posted: Nov 13, 2023
• Last Verified: Nov 1, 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alzheimer Disease; Psychotic Disorders; Mental Disorders

Study Results

No Results Posted as of Nov 13, 2023