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

Purpose

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

  • Psychosis Associated With Alzheimer's Disease

Eligibility

Eligible Ages
Between 55 Years and 90 Years
Eligible Sex
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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

ATP Clinical Research-302 W La Veta Ave
Orange 5379513, California 5332921 92866
Contact:
Gustavo Alva, Site 1001
949-354-5353

Sunwise Clinical Research, LLC - Walnut Creek - IVY - PPDS
Walnut Creek 5406990, California 5332921 94596
Contact:
Ira Glick, Site 1007
925-298-5147

Envision Trials LLC
Bonita Springs 4148533, Florida 4155751 34134-4154
Contact:
Daniel Mandri, Site 1020
305-819-2909

Arrow Clinical Trials
Daytona Beach 4152872, Florida 4155751 32117-5532
Contact:
David Billmeier, Site 1023
386-304-7070

K2 Medical Research - Maitland
Maitland 4163220, Florida 4155751 32751-5669
Contact:
Brandon Lenox, Site 1039
407-670-5833

Premier Clinical Research Institute
Miami 4164138, Florida 4155751 33122-1335
Contact:
Emelina Arocha, Site 1021
305-445-5994

Floridian Neuroscience Institute-1901 SW 1 St
Miami 4164138, Florida 4155751 33135
Contact:
Emilio Mantero-Atienza, Site 1115
305-326-0776

South Florida Research Phase I-IV, Inc. - Miami
Miami 4164138, Florida 4155751 33166
Contact:
Silvia Silva-Duluc, Site 1053
305-669-6166

Novel Clinical Research Center, LLC.
Miami 4164138, Florida 4155751 33173-1474
Contact:
Heber Varela, Site 1006
786-773-2737

Coral Research Clinic & Coral Diagnostic Center
Miami 4164138, Florida 4155751 33186-4643
Contact:
Jorge Paoli Bruno, Site 1054
000-000-0000

K2 Medical Research - Tampa
Tampa 4174757, Florida 4155751 33607-4629
Contact:
Kelley Yokum, Site 1041
813-800-5252

Five Towns Neurology, PC
Woodmere 5145028, New York 5128638 11598-1739
Contact:
David Steiner, Site 1025
516-239-1800

Clinical Trial Network - 7080 Southwest Fwy
Houston 4699066, Texas 4736286 77074-2085
Contact:
Nelson Berrios, Site 1004

More Details

NCT ID
NCT05511363
Status
Recruiting
Sponsor
Karuna Therapeutics

Study Contact

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
855-907-3286
Clinical.Trials@bms.com

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ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center