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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)

NCT05511363 · Karuna Therapeutics, Inc., a Bristol Myers Squibb company
In plain English

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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
About this study
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 or relapse and safety and tolerability in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo.
Eligibility criteria
Inclusion Criteria: * Is aged 55 to 90 years, inclusive, at Screening * 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. i) The subject's legally acceptable representative must provide informed consent; ii) The subject must provide informed consent. * Meets clinical criteria for possible or probable Alzheimer's Disease * 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. * Living at the same location for a minimum of 4 weeks before Screening, with the intention of living at the same location throughout the study. * Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified caregiver or study partner who, in the investigator's judgment, has frequent and sufficient contact with the participant (ie, ≥10 hours per week) on a regular basis to reliably provide accurate information regarding the participant's cognitive, behavioral, and functional status, and is willing to: i) Attend all visits and report on participant's status. ii) Oversee participant compliance with medication and study procedures; iii) Participate in the study assessments and provide informed consent to participate in the study. * History of psychotic symptoms (meeting International Psychogeriatric Association \[IPA\] criteria) for at least 2 months prior to Screening. * 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. * Subjects are required to meet at least one of the following criteria at Screening and Baseline: i) Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR; ii) Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on two of the seven items. * Mini-Mental State Examination (MMSE) score of 6 to 24, inclusive, at Screening * 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. * 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 * BMI must be within 16 to 40 kg/m2 inclusive * 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. Exclusion Criteria: * Psychotic symptoms that are primarily attributable to a condition other than the Alzheimer's Disease causing dementia * History of major depressive episode with psychotic features during the 12 months prior to Screening * History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder * 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 * Significant or severe renal impairment based on a screening cutoff for Estimated Glomerular Filtration Rate (eGFR) of \<50 mL/min * History of ischemic stroke within 12 months prior to Screening or any evidence of hemorrhagic stroke * History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm, unstable thyroid function, or unexplained syncope * Any of the following: i) New York Heart Association Class 2 congestive heart failure; ii) Grade 2 or greater angina pectoris; iii) Sustained ventricular tachycardia; iv) Ventricular fibrillation; v) Torsade de pointes; vi) Implantable cardiac defibrillator. * Myocardial infarction within the 6 months prior to Screening * Personal or family history of symptoms of long QT syndrome as evaluated by the investigator * Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, active biliary disease, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or liver function tests results * History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator * Participants with any of the following: i) History of bladder stones; ii) History of recurrent urinary tract infections; iii) For male participants: 1. Serum prostate specific antigen (PSA) \> 10 ng/mL at Screening 2. An IPSS of 5 (almost always) on items 1, 3, 5, or 6 3. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9 * History of obstructive gastrointestinal disorder, gastric retention, irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months * Risk of suicidal behavior during the study as determined by clinical assessment and/ or C-SSRS * Clinically significant abnormal finding on the physical examination, electrocardiogram, or clinical laboratory results at Screening * 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 * Currently receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), mood stabilizers (eg, lithium) tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam) and unable to complete the washout: i) 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; ii) Mirtazapine or trazodone may be used 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. * 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 * 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 * Unable to taper and discontinue a concomitant medication that would preclude participation in the study * Prior exposure to KarXT * Experienced any significant adverse events due to trospium, including a known hypersensitivity to trospium * 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 * Other protocol-defined Inclusion/Exclusion criteria apply
Study design
Enrollment target: 410 participants
Allocation: randomized
Masking: quadruple
Age groups: adult, older_adult
Timeline
Starts: 2022-08-23
Estimated completion: 2026-10-05
Last updated: 2026-03-24
Interventions
Drug: KarXTDrug: Placebo
Primary outcomes
  • Time from randomization to relapse during the 38-week study (Week 38)
Sponsor
Karuna Therapeutics, Inc., a Bristol Myers Squibb company · industry
Contacts & investigators
ContactBMS Clinical Trials Contact Center www.BMSClinicalTrials.com · contact · Clinical.Trials@bms.com · 855-907-3286
ContactFirst line of the email MUST contain NCT # and Site #. · contact
InvestigatorBristol-Myers Squibb · study_director, Bristol-Myers Squibb
All locations (116)
Local Institution - 1029Active Not Recruiting
Homewood, Alabama, United States
Local Institution - 1044Completed
Phoenix, Arizona, United States
Local Institution - 1033Completed
Encino, California, United States
Local Institution - 1031Withdrawn
Irvine, California, United States
ATP Clinical Research-302 W La Veta AveRecruiting
Orange, California, United States
Local Institution - 1043Completed
Pasadena, California, United States
Local Institution - 1047Active Not Recruiting
San Marcos, California, United States
Sunwise Clinical Research, LLC - Walnut Creek - IVY - PPDSRecruiting
Walnut Creek, California, United States
Local Institution - 1014Completed
Colorado Springs, Colorado, United States
Local Institution - 1013Completed
Stamford, Connecticut, United States
Local Institution - 1011Completed
Boca Raton, Florida, United States
Envision Trials LLCRecruiting
Bonita Springs, Florida, United States
Local Institution - 1015Completed
Bradenton, Florida, United States
K2 Medical Research - Winter GardenRecruiting
Clermont, Florida, United States
Arrow Clinical TrialsRecruiting
Daytona Beach, Florida, United States
Local Institution - 1045Active Not Recruiting
Doral, Florida, United States
Local Institution - 1046Active Not Recruiting
Hialeah, Florida, United States
Local Institution - 1024Withdrawn
Hialeah, Florida, United States
Local Institution - 1052Active Not Recruiting
Hialeah, Florida, United States
Local Institution - 1049Active Not Recruiting
Homestead, Florida, United States
K2 Medical Research - MaitlandRecruiting
Maitland, Florida, United States
Local Institution - 1021Active Not Recruiting
Miami, Florida, United States
Local Institution - 1005Completed
Miami, Florida, United States
Local Institution - 1115Active Not Recruiting
Miami, Florida, United States
Local Institution - 1010Completed
Miami, Florida, United States
Local Institution - 1143Active Not Recruiting
Miami, Florida, United States
Local Institution - 1009Active Not Recruiting
Miami, Florida, United States
Local Institution - 1129Active Not Recruiting
Miami, Florida, United States
Local Institution - 1053Active Not Recruiting
Miami, Florida, United States
Local Institution - 1006Active Not Recruiting
Miami, Florida, United States
Local Institution - 1111Active Not Recruiting
Miami, Florida, United States
Local Institution - 1054Active Not Recruiting
Miami, Florida, United States
Local Institution - 1042Active Not Recruiting
Miami, Florida, United States
Local Institution - 1032Active Not Recruiting
Miami Lakes, Florida, United States
Local Institution - 1026Active Not Recruiting
Miami Springs, Florida, United States
Local Institution - 1027Withdrawn
Ocala, Florida, United States
Local Institution - 1012Completed
Pensacola, Florida, United States
Local Institution - 1008Active Not Recruiting
St. Petersburg, Florida, United States
University of South FloridaRecruiting
Tampa, Florida, United States
Local Institution - 1041Completed
Tampa, Florida, United States
Local Institution - 1040Withdrawn
The Villages, Florida, United States
Local Institution - 1037Completed
Chicago, Illinois, United States
Local Institution - 1018Active Not Recruiting
Manhasset, New York, United States
Local Institution - 1030Withdrawn
New York, New York, United States
Local Institution - 1051Completed
New York, New York, United States
Local Institution - 1017Completed
New York, New York, United States
Local Institution - 1002Active Not Recruiting
Staten Island, New York, United States
Local Institution - 1034Completed
Stony Brook, New York, United States
Five Towns Neurology, PCRecruiting
Woodmere, New York, United States
Local Institution - 1003Withdrawn
Canton, Ohio, United States
Local Institution - 1028Withdrawn
Oklahoma City, Oklahoma, United States
Local Institution - 1016Completed
Oklahoma City, Oklahoma, United States
Local Institution - 1019Active Not Recruiting
Allentown, Pennsylvania, United States
Local Institution - 1035Active Not Recruiting
Charleston, South Carolina, United States
Local Institution - 1038Completed
Franklin, Tennessee, United States
Local Institution - 1022Completed
Flower Mound, Texas, United States
Local Institution - 1036Completed
Frisco, Texas, United States
Clinical Trial Network - 7080 Southwest FwyRecruiting
Houston, Texas, United States
Medical Center Sveti Naum EOODRecruiting
Sofia, Sofia-Grad, Bulgaria
Local Institution - 4505Completed
Sofia, Sofia-Grad, Bulgaria
Local Institution - 4502Completed
Sofia, Sofia-Grad, Bulgaria
Medical Center Medconsult Pleven OODRecruiting
Pleven, Bulgaria
Local Institution - 4504Completed
Vratsa, Bulgaria
Local Institution - 4103Completed
Zagreb, City of Zagreb, Croatia
Local Institution - 4105Active Not Recruiting
Zagreb, City of Zagreb, Croatia
Polyclinic NeuronRecruiting
Zagreb, City of Zagreb, Croatia
Local Institution - 4101Active Not Recruiting
Zagreb, City of Zagreb, Croatia
Psychiatric Clinic Sveti IvanRecruiting
Zagreb, City of Zagreb, Croatia
CLINTRIAL s.r.o.Recruiting
Prague, Praha, Hlavní Mesto, Czechia
Local Institution - 4003Withdrawn
Brno, South Moravian, Czechia
Neuroterapie KH, s.r.oRecruiting
Kutná Hora, Czechia
A-SHINE s.r.o.Recruiting
Pilsen, Czechia
Local Institution - 4004Completed
Prague, Czechia
Vestra Clinics s.r.o.Recruiting
Rychnov nad Kněžnou, Czechia
Local Institution - 2501Active Not Recruiting
Reims, Marne, France
Local Institution - 2502Active Not Recruiting
Dijon, France
Local Institution - 2503Completed
Rouen, France
Local Institution - 2401Completed
Böblingen, Baden-Wurttemberg, Germany
Local Institution - 2403Withdrawn
Bayreuth, Bavaria, Germany
Local Institution - 2402Withdrawn
Homburg, Saarland, Germany
Local Institution - 2301Completed
Rome, Lazio, Italy
Azienda Ospedaliero-Universitaria di Modena - Policlinico di ModenaRecruiting
Baggiovara, Modena, Italy
Local Institution - 2307Active Not Recruiting
Ponderano (Biella), Piedmont, Italy
Local Institution - 2308Completed
Florence, Tuscany, Italy
Local Institution - 2304Completed
Milan, Italy
Local Institution - 2305Completed
Monza, Italy
Local Institution - 2302Completed
Pisa, Italy
Local Institution - 2303Active Not Recruiting
Roma, Italy
Local Institution - 2309Completed
Roma, Italy
University Clinical Center of Serbia - Pasterova 2 - PPDSRecruiting
Belgrade, Belgrade, Serbia
Clinical Hospital Center Dragisa Misovic DedinjeRecruiting
Belgrade, Serbia
Local Institution - 4307Completed
Belgrade, Serbia
Military Medical AcademyRecruiting
Belgrade, Serbia
Military Medical AcademyRecruiting
Belgrade, Serbia
Local Institution - 4305Active Not Recruiting
Kovin, Serbia
University Clinical Center KragujevacRecruiting
Kragujevac, Serbia
University Clinical Center KragujevacRecruiting
Kragujevac, Serbia
University Clinical Center KragujevacRecruiting
Kragujevac, Serbia
Clinical Centre of VojvodinaRecruiting
Novi Sad, Serbia
Local Institution - 4311Completed
Vršac, Serbia
Univerzitna nemocnica L Pasteura Kosice-Rastislavova 43Recruiting
Košice, Košice Region, Slovakia
MUDr. Beata Dupejova, Neurologicka ambulancia, s.r.o.Recruiting
Banská Bystrica, Slovakia
KONZILIUM s.r.oRecruiting
Dubnica nad Váhom, Slovakia
EPAMED s.r.oRecruiting
Košice, Slovakia
Crystal Comfort, s.r.o.Recruiting
Vranov nad Topľou, Slovakia
Local Institution - 4404Withdrawn
Žilina, Slovakia
Local Institution - 2205Completed
Barcelona, Spain
Local Institution - 2207Active Not Recruiting
Madrid, Spain
Complejo Asistencial Universitario de Salamanca - H. ClinicoRecruiting
Salamanca, Spain
Hospital Victoria EugeniaRecruiting
Seville, Spain
Hospital Universitario Rio HortegaRecruiting
Valladolid, Spain
Hospital Provincial de ZamoraRecruiting
Zamora, Spain
Hospital Viamed MontecanalRecruiting
Zaragoza, Spain
Local Institution - 2103Withdrawn
Swindon, Wiltshire, United Kingdom
Local Institution - 2105Withdrawn
Aberdeen, United Kingdom
Local Institution - 2104Withdrawn
Motherwell, United Kingdom
A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1) · TrialPath