Clinical trial NCT05511363: A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Psychosis Associated With Alzheimer's Disease
Lead sponsor: Karuna Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-08-23
Enrollment: 380
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Time from randomization to relapse during the 38-week study
timeFrame: Week 38
Secondary outcomes:
measure: Time from randomization to discontinuation for any reason during the 38-week study
timeFrame: Week 38
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Tilda Alabama - PPDS
state: Alabama
city: Phoenix
country: United States
facility: IMA Clinical Research - Phoenix - PPDS
state: Arizona
city: Encino
country: United States
facility: Asclepes Research
state: California
city: Irvine
country: United States
facility: Local Institution - 1031
state: California
city: Orange
country: United States
facility: ATP Clinical Research-302 W La Veta Ave
state: California
city: Pasadena
country: United States
facility: SC3 Research - Pasadena - 960 E. Green St
state: California
city: San Marcos
country: United States
facility: The Neuron Clinic
state: California
city: Walnut Creek
country: United States
facility: Sunwise Clinical Research, LLC - Walnut Creek - IVY - PPDS
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Neurological Associates
state: Colorado
city: Stamford
country: United States
facility: Ki Health Partners LLC DBA New England Institute for Clinical Research
state: Connecticut
city: Boca Raton
country: United States
facility: South Florida Neurology Associates
state: Florida
city: Bonita Springs
country: United States
facility: Envision Trials LLC
state: Florida
city: Bradenton
country: United States
facility: Local Institution - 1015
state: Florida
city: Clermont
country: United States
facility: K2 Medical Research - Winter Garden
state: Florida
city: Daytona Beach
country: United States
facility: Arrow Clinical Trials
state: Florida
city: Doral
country: United States
facility: Betancourt Research Services
state: Florida
city: Hialeah
country: United States
facility: United Research Institute
state: Florida
city: Hialeah
country: United States
facility: Local Institution - 1024
state: Florida
city: Hialeah
country: United States
facility: Las Mercedes Medical Research - 4440 West 16th Ave
state: Florida
city: Homestead
country: United States
facility: Coral Clinic Research
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research - Maitland
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic Inc
state: Florida
city: Miami Springs
country: United States
facility: Ocean Blue Medical Research Center Inc
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research Phase I - IV
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute - Miami - ClinEdge - PPDS
state: Florida
city: Miami
country: United States
facility: Global Medical Institutes, LLC - Miami - ClinEdge - PPDS
state: Florida
city: Miami
country: United States
facility: Dade Research Center
state: Florida
city: Miami
country: United States
facility: Floridian Neuroscience Institute-1901 SW 1 St
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Miami
country: United States
facility: MedOne Clinical Research LLC
state: Florida
city: Miami
country: United States
facility: Allied Biomedical Research Institute
state: Florida
city: Miami
country: United States
facility: Future Care Solution LLC
state: Florida
city: Miami
country: United States
facility: Local Institution - 1006
state: Florida
city: Miami
country: United States
facility: Coral Research Clinic & Coral Diagnostic Center
state: Florida
city: Miami
country: United States
facility: ONHEALTH Research Center
state: Florida
city: Ocala
country: United States
facility: Local Institution - 1027
state: Florida
city: Pensacola
country: United States
facility: Emerald Coast Center for Neurological Disorders
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates Inc
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: K2 Medical Research - Tampa
state: Florida
city: The Villages
country: United States
facility: Local Institution - 1040
state: Florida
city: Chicago
country: United States
facility: Research Network America - Chicago - 3845 W 26th St
state: Illinois
city: Manhasset
country: United States
facility: The Feinstein Institutes for Medical Research - BRANY - PPDS
state: New York
city: New York
country: United States
facility: Local Institution - 1030
state: New York
city: New York
country: United States
facility: Columbia University Medical Center (CUMC)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates - 4349 Hylan Blvd
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Woodmere
country: United States
facility: Five Towns Neurology, PC
state: New York
city: Canton
country: United States
facility: Local Institution - 1003
state: Ohio
city: Oklahoma City
country: United States
facility: Local Institution - 1028
state: Oklahoma
city: Oklahoma City
country: United States
facility: Local Institution - 1016
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research - 1245 S. Cedar Crest Blvd
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) - PPDS
state: South Carolina
city: Franklin
country: United States
facility: KCA Neurology, PLLC
state: Tennessee
city: Flower Mound
country: United States
facility: North Pointe Psychiatry - Flower Mound
state: Texas
city: Frisco
country: United States
facility: Beautiful Minds
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network - 7080 Southwest Fwy
state: Texas
city: Sofia
country: Bulgaria
facility: Medical Center Sveti Naum EOOD
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD - PPDS
state: Sofia-Grad
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven OOD
city: Vratsa
country: Bulgaria
facility: Center for Mental Health - Vratsa
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Poliklinika Bonifarm-Hondlova 2/10
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Polyclinic Neuron
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Klinika za psihijatriju Vrapce
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Psychiatric Clinic Sveti Ivan
state: Grad Zagreb
city: Brno
country: Czechia
facility: Local Institution - 4003
state: Jihomoravský Kraj
city: Praha
country: Czechia
facility: CLINTRIAL s.r.o.
state: Praha, Hlavní Mesto
city: Kutná Hora
country: Czechia
facility: Neuroterapie KH, s.r.o
city: Plzeň
country: Czechia
facility: A-SHINE s.r.o.
city: Praha 4
country: Czechia
facility: Clinoxus s.r.o.
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics s.r.o.
city: Reims
country: France
facility: CHU de Reims Hôpital Robert Debré
state: Marne
city: Dijon
country: France
facility: CHRU Dijon Hopital General
city: Rouen
country: France
facility: CHU de Rouen - Hôpital Charles-Nicolle
city: Böblingen
country: Germany
facility: Local Institution - 2401
state: Baden-Württemberg
city: Bayreuth
country: Germany
facility: Local Institution - 2403
state: Bayern
city: Homburg
country: Germany
facility: Local Institution - 2402
state: Saarland
city: Roma
country: Italy
facility: Fondazione Santa Lucia IRCCS
state: Lazio
city: Baggiovara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena - Policlinico di Modena
state: Modena
city: Ponderano (Biella)
country: Italy
facility: ASL Biella - Ospedale degli Infermi
state: Piemonte
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli - Rome - PPDS
city: Roma
country: Italy
facility: Azienda Ospedaliero-Universitaria Sant'Andrea
city: Beograd
country: Serbia
facility: University Clinical Center of Serbia - Pasterova 2 - PPDS
state: Belgrade
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Dragisa Misovic Dedinje
city: Belgrade
country: Serbia
facility: Institute of Mental Health-Milana Kasanina 3
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Kovin
country: Serbia
facility: Special Hospital for Psychiatric Diseases Kovin
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Vršac
country: Serbia
facility: Special Hospital ''Dr Slavoljub Bakalovic''
city: Kosice
country: Slovakia
facility: Univerzitna nemocnica L Pasteura Kosice-Rastislavova 43
state: Košický Kraj
city: Banská Bystrica
country: Slovakia
facility: MUDr. Beata Dupejova, Neurologicka ambulancia, s.r.o.
city: Dubnica nad Váhom
country: Slovakia
facility: KONZILIUM s.r.o
city: Košice
country: Slovakia
facility: EPAMED s.r.o
city: Vranov nad Topľou
country: Slovakia
facility: Crystal Comfort, s.r.o.
city: Žilina
country: Slovakia
facility: Local Institution - 4404
city: Barcelona
country: Spain
facility: Ace Alzheimer Center Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - H. Clinico
city: Sevilla
country: Spain
facility: Hospital Victoria Eugenia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Zamora
country: Spain
facility: Hospital Provincial de Zamora
city: Zaragoza
country: Spain
facility: Hospital Viamed Montecanal
city: Swindon
country: United Kingdom
facility: Local Institution - 2103
state: Wiltshire
city: Aberdeen
country: United Kingdom
facility: Local Institution - 2105
city: Motherwell
country: United Kingdom
facility: Local Institution - 2104
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: