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NCT05511363PHASE3Recruiting

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

Karuna Therapeutics, Inc., a Bristol Myers Squibb company

Start Date

8/23/2022

Completion Date

10/5/2026

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

Eligibility Criteria

Age Range: 55 years to 90 years

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

Interventions

DRUG

KarXT

DRUG

Placebo

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Conditions

Psychosis Associated With Alzheimer's Disease

Locations

Local Institution - 1029

Homewood, Alabama 35209-6809

United States

Local Institution - 1044

Phoenix, Arizona 85012-2836

United States

Local Institution - 1033

Encino, California 91436-2201

United States

Local Institution - 1031

Irvine, California 92612-1246

United States

ATP Clinical Research-302 W La Veta Ave

Orange, California 92866

United States

Local Institution - 1043

Pasadena, California 91106

United States

Local Institution - 1047

San Marcos, California 92069-3595

United States

Sunwise Clinical Research, LLC - Walnut Creek - IVY - PPDS

Walnut Creek, California 94596

United States

Local Institution - 1014

Colorado Springs, Colorado 80907-5302

United States

Local Institution - 1013

Stamford, Connecticut 06905-1206

United States

Local Institution - 1011

Boca Raton, Florida 33487-2768

United States

Local Institution - 1020

Bonita Springs, Florida 34134

United States

Local Institution - 1015

Bradenton, Florida 34209-4687

United States

K2 Medical Research - Winter Garden

Clermont, Florida 34711-5933

United States

Arrow Clinical Trials

Daytona Beach, Florida 32117-5532

United States

Local Institution - 1045

Doral, Florida 33172-2638

United States

Local Institution - 1046

Hialeah, Florida 33012-5826

United States

Local Institution - 1024

Hialeah, Florida 33012-5884

United States

Local Institution - 1052

Hialeah, Florida 33012

United States

Local Institution - 1049

Homestead, Florida 33032

United States

K2 Medical Research - Maitland

Maitland, Florida 32751-5669

United States

Local Institution - 1021

Miami, Florida 33122-1335

United States

Local Institution - 1005

Miami, Florida 33125-3724

United States

Local Institution - 1115

Miami, Florida 33135

United States

Local Institution - 1010

Miami, Florida 33137

United States

Local Institution - 1143

Miami, Florida 33145-2455

United States

Local Institution - 1009

Miami, Florida 33155-4630

United States

Local Institution - 1129

Miami, Florida 33165-3947

United States

Local Institution - 1053

Miami, Florida 33166

United States

Local Institution - 1006

Miami, Florida 33173-1474

United States

Local Institution - 1111

Miami, Florida 33173

United States

Local Institution - 1054

Miami, Florida 33186-4643

United States

Local Institution - 1042

Miami, Florida 33186-5882

United States

Local Institution - 1032

Miami Lakes, Florida 33014-5602

United States

Local Institution - 1026

Miami Springs, Florida 33166-5260

United States

Local Institution - 1027

Ocala, Florida 34470-6657

United States

Local Institution - 1012

Pensacola, Florida 32504-8608

United States

Local Institution - 1008

St. Petersburg, Florida 33713-8844

United States

University of South Florida

Tampa, Florida 33606

United States

Local Institution - 1041

Tampa, Florida 33607-4629

United States

Local Institution - 1040

The Villages, Florida 32159-8986

United States

Local Institution - 1037

Chicago, Illinois 60623

United States

Local Institution - 1018

Manhasset, New York 11030-3816

United States

Local Institution - 1-14IL3BJP

New York, New York 10003-1759

United States

Local Institution - 1030

New York, New York 10016

United States

Local Institution - 1051

New York, New York 10032-3720

United States

Local Institution - 1017

New York, New York 10032

United States

Local Institution - 1002

Staten Island, New York 10314-1607

United States

Local Institution - 1034

Stony Brook, New York 11794-0001

United States

Five Towns Neurology, PC

Woodmere, New York 11598-1739

United States

Local Institution - 1003

Canton, Ohio 44718

United States

Local Institution - 1028

Oklahoma City, Oklahoma 73104-5007

United States

Local Institution - 1016

Oklahoma City, Oklahoma 73112

United States

Local Institution - 1019

Allentown, Pennsylvania 18103

United States

Local Institution - 1035

Charleston, South Carolina 29425-8900

United States

Local Institution - 1038

Franklin, Tennessee 37067-5922

United States

Local Institution - 1022

Flower Mound, Texas 75028-2011

United States

Local Institution - 1036

Frisco, Texas 75034-6262

United States

Clinical Trial Network - 7080 Southwest Fwy

Houston, Texas 77074-2085

United States

Local Institution - 4505

Sofia, Sofia-Grad 1431

Bulgaria

Local Institution - 4502

Sofia, Sofia-Grad 1510

Bulgaria

Local Institution - 4506

Cherven Bryag, 5980

Bulgaria

Medical Center Medconsult Pleven OOD

Pleven, 5800

Bulgaria

Medical Center Sveti Naum EOOD

Sofia, 1113

Bulgaria

Local Institution - 1-14IBHZ4D

Stara Zagora, 6003

Bulgaria

Local Institution - 4504

Vratsa, 3000

Bulgaria

Local Institution - 1-14JRHMIY

Zagreb, City of Zagreb 10000

Croatia

Local Institution - 4103

Zagreb, City of Zagreb 10000

Croatia

Local Institution - 4105

Zagreb, City of Zagreb 10000

Croatia

Polyclinic Neuron

Zagreb, City of Zagreb 10000

Croatia

Local Institution - 4101

Zagreb, City of Zagreb 10090

Croatia

Psychiatric Clinic Sveti Ivan

Zagreb, City of Zagreb 10090

Croatia

CLINTRIAL s.r.o.

Prague, Praha, Hlavní Mesto 100 00

Czechia

Local Institution - 4003

Brno, South Moravian 628 00

Czechia

Local Institution - 4001

Kutná Hora, 284 01

Czechia

A-SHINE s.r.o.

Pilsen, 301 00

Czechia

Local Institution - 1-14IL3BFV

Prague, 109 00

Czechia

Local Institution - 4004

Prague, 140 00

Czechia

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, 516 01

Czechia

Local Institution - 2501

Reims, Marne 51100

France

Local Institution - 1-14ILFZ33

Villeurbanne, Rhône 69100

France

Local Institution - 2502

Dijon, 21079

France

Local Institution - 2503

Rouen, 76000

France

Local Institution - 2401

Böblingen, Baden-Wurttemberg 71034

Germany

Local Institution - 2403

Bayreuth, Bavaria 95445

Germany

Local Institution - 2402

Homburg, Saarland 66424

Germany

Local Institution - 1-14IL3BK3

Ahmedabad, Gujarat 380061

India

Local Institution - 1-14IW4MUN

New Delhi, National Capital Territory of Delhi 110029

India

Local Institution - 1-14IW4MT8

Hyderabad, 500034

India

Local Institution - 1-14ILFYZQ

Salerno, Campania 84131

Italy

Local Institution - 2301

Rome, Lazio 00179

Italy

Azienda Ospedaliero-Universitaria di Modena - Policlinico di Modena

Baggiovara, Modena 41126

Italy

Local Institution - 2307

Ponderano (Biella), Piedmont 13875

Italy

Local Institution - 2308

Florence, Tuscany 50139

Italy

Local Institution - 2304

Milan, 20121

Italy

Local Institution - 2305

Monza, 20900

Italy

Local Institution - 2302

Pisa, 56126

Italy

Local Institution - 2303

Roma, 00168

Italy

Local Institution - 2309

Roma, 00189

Italy

University Clinical Center of Serbia - Pasterova 2 - PPDS

Belgrade, Belgrade 11000

Serbia

Clinical Hospital Center Dragisa Misovic Dedinje

Belgrade, 11000

Serbia

Local Institution - 4307

Belgrade, 11000

Serbia

Military Medical Academy

Belgrade, 11000

Serbia

Military Medical Academy

Belgrade, 11000

Serbia

Local Institution - 4305

Kovin, 26220

Serbia

University Clinical Center Kragujevac

Kragujevac, 34000

Serbia

University Clinical Center Kragujevac

Kragujevac, 34000

Serbia

University Clinical Center Kragujevac

Kragujevac, 34000

Serbia

Clinical Centre of Vojvodina

Novi Sad, 21000

Serbia

Local Institution - 4311

Vršac, 26300

Serbia

Univerzitna nemocnica L Pasteura Kosice-Rastislavova 43

Košice, Košice Region 041 90

Slovakia

MUDr. Beata Dupejova, Neurologicka ambulancia, s.r.o.

Banská Bystrica, 974 04

Slovakia

KONZILIUM s.r.o

Dubnica nad Váhom, 018 41

Slovakia

EPAMED s.r.o

Košice, 040 01

Slovakia

Crystal Comfort, s.r.o.

Vranov nad Topľou, 093 01

Slovakia

Local Institution - 4404

Žilina, 012 07

Slovakia

Local Institution - 1-14IG4A3I

Pusan, Busan Gwangyeogsi 49241

South Korea

Local Institution - 1-14IVVWPL

Junggu, Incheon Gwang'yeogsi 22332

South Korea

Local Institution - 1-14IG4A1R

Seoul, Seoul Teugbyeolsi 05505

South Korea

Local Institution - 2205

Barcelona, 8028

Spain

Local Institution - 2207

Madrid, 28006

Spain

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, 37007

Spain

Hospital Victoria Eugenia

Seville, 41009

Spain

Hospital Universitario Rio Hortega

Valladolid, 47012

Spain

Hospital Provincial de Zamora

Zamora, 49021

Spain

Hospital Viamed Montecanal

Zaragoza, 50012

Spain

Local Institution - 2103

Swindon, Wiltshire SN3 6BW

United Kingdom

Local Institution - 2105

Aberdeen, AB25 2ZL

United Kingdom

Local Institution - 2104

Motherwell, ML1 4UF

United Kingdom