- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05511363
A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1) (ADEPT-1)
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
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Karuna Medical Information
- Phone Number: 1-888-783-0380
- Email: medinfo@karunatx.com
Study Locations
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Pleven, Bulgaria, 5800
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Sofia, Bulgaria, 1113
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Sofia, Bulgaria, 1510
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Sofia, Bulgaria, 1431
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Vratsa, Bulgaria, 3000
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Zagreb, Croatia, 10000
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Zagreb, Croatia, 10090
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Kutná Hora, Czechia, 284 01
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Plzen, Czechia, 301 00
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Praha, Czechia, 108 00
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Praha, Czechia, 140 00
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Rychnov Nad Kněžnou, Czechia, 516 01
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Dijon, France, 21000
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Rouen, France, 76031
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Marne
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Reims, Marne, France, 51092
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Baden-Württemberg
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Böblingen, Baden-Württemberg, Germany, 71034
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Modena, Italy, 41126
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Roma, Italy, 00179
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Roma, Italy, 56126
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Biella
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Ponderano, Biella, Italy, 13875
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Lazio
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Roma, Lazio, Italy, 00168
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Lombardy
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Milano, Lombardy, Italy, 20122
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Monza, Lombardy, Italy, 20900
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Tuscany
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Firenze, Tuscany, Italy, 50139
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Belgrad, Serbia, 11000
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Belgrade, Serbia, 11000
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Kovin, Serbia, 26220
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Kragujevac, Serbia, 34000
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Vršac, Serbia, 26300
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Vojvodina
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Novi Sad, Vojvodina, Serbia, 21000
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Banská Bystrica, Slovakia, 97404
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Dubnica Nad Váhom, Slovakia, 018 41
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Košice, Slovakia, 040 11
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Košice, Slovakia, 041 90
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Vranov Nad Topľou, Slovakia, 093 01
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Barcelona, Spain, 08028
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Madrid, Spain, 28006
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Salamanca, Spain, 37007
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Sevilla, Spain, 41009
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Valladolid, Spain, 47012
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Zamora, Spain, 49021
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Zaragoza, Spain, 50012
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Alabama
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Homewood, Alabama, United States, 35209
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California
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Costa Mesa, California, United States, 92626
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Encino, California, United States, 91436
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Lafayette, California, United States, 94549
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Colorado
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Colorado Springs, Colorado, United States, 80907
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Connecticut
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Stamford, Connecticut, United States, 06905
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Florida
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Boca Raton, Florida, United States, 33487
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Bonita Springs, Florida, United States, 34134
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Bradenton, Florida, United States, 34209
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Daytona Beach, Florida, United States, 32117
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Hialeah, Florida, United States, 33012
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Maitland, Florida, United States, 32751
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Miami, Florida, United States, 33125
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Miami, Florida, United States, 33173
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Miami, Florida, United States, 33186
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Miami, Florida, United States, 33155
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Miami, Florida, United States, 33137
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Miami, Florida, United States, 33122
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Miami Lakes, Florida, United States, 33014
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Miami Springs, Florida, United States, 33166
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Pensacola, Florida, United States, 32504
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Saint Petersburg, Florida, United States, 33713
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Tampa, Florida, United States, 33607
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Illinois
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Berwyn, Illinois, United States, 60402
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New York
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Manhasset, New York, United States, 11030
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New York, New York, United States, 10032
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Staten Island, New York, United States, 10312
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Woodmere, New York, United States, 11598
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73112
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Pennsylvania
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Allentown, Pennsylvania, United States, 18104
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South Carolina
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Charleston, South Carolina, United States, 29425
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Tennessee
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Franklin, Tennessee, United States, 37067
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Texas
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Frisco, Texas, United States, 75034
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Houston, Texas, United States, 77074
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Lewisville, Texas, United States, 75057
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
- The subject's legally acceptable representative or caregiver/study partner, if local regulations allow, must provide informed consent
- The subject must provide informed assent
- 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 home or residential assisted-living facility for a minimum of six weeks before Screening
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:
- Attend all visits and report on subject's status
- Oversee subject compliance with medication and study procedures
- 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:
- Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR
- 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 8 to 22, 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 18 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. Sperm donation is not allowed for 30 days after the final dose of the 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 <60 mL/min/1.73 m2
- 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:
- New York Heart Association Class 2 congestive heart failure
- Grade 2 or greater angina pectoris
- Sustained ventricular tachycardia
- Ventricular fibrillation
- Torsade de pointes
- 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, 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
For males only, any one of the following:
- History of bladder stones
- History of recurrent urinary tract infections
- Serum prostate specific antigen (PSA) > 10 ng/mL at Screening
- An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1, 3, 5, or 6
- A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9
- History of 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
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)
- 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
- 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.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: KarXT
Xanomeline and Trospium Chloride Capsules
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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
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Placebo Comparator: Placebo
Placebo Capsules
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Placebo Capsules
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Time from randomization to relapse during the 38-week study
Time Frame: Week 38
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Week 38
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Time from randomization to discontinuation for any reason during the 38-week study
Time Frame: Week 38
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Week 38
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Ronald Marcus, MD, Karuna Therapeutics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- KAR-031
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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