RecruitingPhase 3

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
55 Years to 90 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This 38-week study tests whether KarXT can keep psychosis symptoms from coming back in people ages 55 to 90 with Alzheimer's disease. Psychosis means seeing or hearing things that are not there, or having false beliefs. The study also compares KarXT's safety with a placebo, a treatment with no active drug.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 55 to 90 years old and have possible or likely Alzheimer's disease.
  • Have psychosis for at least 2 months, with at least moderate symptoms that meet the study's rating rules.
  • Have a memory and thinking test score of 6 to 24. Have a brain scan from the past 5 years, taken after dementia began, or get one during screening.
  • Give written consent, or have a legal representative give consent and agree yourself where required. Be able to follow study rules and attend visits.
  • Have lived in the same place for at least 4 weeks and plan to stay there during the study.
  • Be able to move around, with or without a walking aid. Have a caregiver with about 7 or more hours of contact each week who agrees to attend visits, report symptoms, and help with medicines and study tasks.
  • If taking certain Alzheimer's medicines, keep the dose steady for at least 6 weeks before screening and during the study. Meet the study's body size and weight limits.
  • Not be pregnant or breastfeeding. If able to become pregnant, use highly effective birth control during the study and for at least one menstrual cycle after the last dose.

Who can't join

  • Psychosis mainly caused by something other than Alzheimer's disease; depression with psychosis in the past year; or a history of bipolar disorder, schizophrenia, or schizoaffective disorder.
  • Serious illness or abnormal exam, heart test, or blood test results that could make the study unsafe or affect results. This includes certain kidney, liver, lung, or other major health problems.
  • A stroke from a blocked blood vessel in the past year, any signs of a bleeding stroke, or certain other brain conditions, including epilepsy or a brain tumor.
  • Certain heart conditions, an implanted heart shock device, a heart attack in the past 6 months, or a personal or family history of long QT syndrome, a heart rhythm problem.
  • Trouble emptying the bladder or stomach, or high risk of these problems; certain types of glaucoma; bladder stones; repeated urine infections; certain prostate test results; blocked bowels; irritable bowel syndrome; or serious constipation treated in the past 6 months.
  • Risk of suicide during the study, or a positive COVID-19 test within 2 weeks before or at screening.
  • Use of medicines not allowed by the study that cannot be stopped, or a positive drug screen without an allowed exception. Some antidepressants, anxiety medicines, and limited cannabis use may be allowed.
  • Past use of KarXT, a serious reaction or allergy to trospium, or use of an experimental drug in another study within 3 months before screening.

Simplified for readability. The official criteria below are what the study team uses.

Official 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 assent or similar where permitted per local law/regulation and as approved by the IRB/IEC. * 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, ≥ approximately 7 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. * Participant is willing and able to attend the study visit for the study duration, follow instructions, and comply with the protocol requirements * BMI must be within 16 to 40 kg/m2 and participants with a BMI of 16 to \<18 kg/m2 must have a body weight ≥40 kg. * A female (as assigned at birth) is eligible to participate if she is not pregnant or breastfeeding. Individual of childbearing potential (IOCBP) 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. 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 sites (59)

AL

AZ

CA

CO

CT

FL

IL

NY

OH

OK

PA

SC

TN

TX