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Trial record 1 of 1 for:    KAR-031
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A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1) (ADEPT-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05511363
Recruitment Status : Recruiting
First Posted : August 23, 2022
Last Update Posted : June 21, 2024
Information provided by (Responsible Party):
Karuna Therapeutics

Brief Summary:

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 and safety and tolerability in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 23, 2022
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : April 30, 2025

Arm Intervention/treatment
Experimental: KarXT
Xanomeline and Trospium Chloride Capsules
Drug: KarXT
KarXT 20 mg/2 mg TID KarXT 30 mg/3 mg TID KarXT 40 mg/4 mg TID KarXT 50 mg/5 mg TID KarXT 66.7/6.67 mg TID

Placebo Comparator: Placebo
Placebo Capsules
Drug: Placebo
Placebo Capsules

Primary Outcome Measures :
  1. Time from randomization to relapse during the 38-week study [ Time Frame: Week 38 ]

Secondary Outcome Measures :
  1. Time from randomization to discontinuation for any reason during the 38-week study [ Time Frame: Week 38 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Is aged 55 to 90 years, inclusive, at Screening
  2. 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.

    1. The subject's legally acceptable representative or caregiver/study partner, if local regulations allow, must provide informed consent
    2. The subject must provide informed assent
  3. Meets clinical criteria for possible or probable Alzheimer's Disease
  4. 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.
  5. Living at the same home or residential assisted-living facility for a minimum of six weeks before Screening
  6. Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified or proxy caregiver (spends approximately 10 hours/week with the subject) that is willing to:

    1. Attend all visits and report on subject's status
    2. Oversee subject compliance with medication and study procedures
    3. Participate in the study assessments and provide informed consent to participate in the study
  7. History of psychotic symptoms (meeting International Psychogeriatric Association [IPA] criteria) for at least 2 months prior to Screening.
  8. 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.
  9. Subjects are required to meet at least one of the following criteria at Screening and Baseline:

    1. Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR
    2. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on two of the seven items.
  10. Mini-Mental State Examination (MMSE) score of 8 to 22, inclusive, at Screening
  11. 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.
  12. 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
  13. BMI must be within 18 to 40 kg/m2 inclusive
  14. 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. Sperm donation is not allowed for 30 days after the final dose of the IMP or matching placebo.

Exclusion Criteria:

  1. Psychotic symptoms that are primarily attributable to a condition other than the Alzheimer's Disease causing dementia
  2. History of major depressive episode with psychotic features during the 12 months prior to Screening
  3. History of a diagnosis 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. Significant or severe renal impairment based on a screening cutoff for Estimated Glomerular Filtration Rate (eGFR) of <60 mL/min/1.73 m2
  6. History of ischemic stroke within 12 months prior to Screening or any evidence of hemorrhagic stroke
  7. History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm, unstable thyroid function, or unexplained syncope
  8. Any of the following:

    1. New York Heart Association Class 2 congestive heart failure
    2. Grade 2 or greater angina pectoris
    3. Sustained ventricular tachycardia
    4. Ventricular fibrillation
    5. Torsade de pointes
    6. Implantable cardiac defibrillator
  9. Myocardial infarction within the 6 months prior to Screening
  10. Personal or family history of symptoms of long QT syndrome as evaluated by the investigator
  11. Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or liver function tests results
  12. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator
  13. For males only, any one of the following:

    1. History of bladder stones
    2. History of recurrent urinary tract infections
    3. Serum prostate specific antigen (PSA) > 10 ng/mL at Screening
    4. An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1, 3, 5, or 6
    5. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9
  14. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
  15. Risk of suicidal behavior during the study as determined by clinical assessment and/ or C-SSRS
  16. Clinically significant abnormal finding on the physical examination, electrocardiogram, or clinical laboratory results at Screening
  17. Urine toxicology screen is positive substances other than cannabis or benzodiazepines (both cannabis and short-or medium-acting benzodiazepines are allowed in limited quantities during the study) unless approval has been given by the Medical Monitor
  18. Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), lithium, tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate)

    1. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening may be permitted
    2. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening. If needed, an extension (up to two weeks) of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor.
  19. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements
  20. Positive test for coronavirus (COVID-19) within 2 weeks before or at Screening; antigen or PCR local testing can be done at the discretion of the Investigator
  21. Unable to taper and discontinue a concomitant medication that would preclude participation in the study
  22. Prior exposure to KarXT
  23. Experienced any significant adverse events due to trospium, including a known hypersensitivity to trospium
  24. 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 past year

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05511363

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Contact: BMS Clinical Trials Contact Center 855-907-3286
Contact: First line of the email MUST contain the NCT# and Site #.

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Sponsors and Collaborators
Karuna Therapeutics
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Additional Information:
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Responsible Party: Karuna Therapeutics Identifier: NCT05511363    
Other Study ID Numbers: CN012-0026
CN012-0026 ( Other Identifier: Bristol-Myers Squibb Protocol ID )
KAR-031 ( Other Identifier: Karuna Pharmaceuticals Protocol ID )
First Posted: August 23, 2022    Key Record Dates
Last Update Posted: June 21, 2024
Last Verified: June 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Psychotic Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Schizophrenia Spectrum and Other Psychotic Disorders