Recruiting NCT05511363

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

Phase III Interventional Psychosis Associated With Alzheimer's Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: KarXT, Placebo.
Who it may be relevant to: Registry conditions: Psychosis Associated With Alzheimer's Disease. Basic parameters: 55 years — 90 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Bulgaria, Croatia, Czechia, France +8
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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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

Overview

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.

Interventions

Drug KarXT
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
Drug Placebo
Placebo Capsules

Primary outcome measures

Time from randomization to relapse during the 38-week study [Time frame: Week 38]

Secondary outcome measures (12)

Time from randomization to first occurrence of treatment discontinuation for any reason or relapse during the 38-week study [Time frame: Week 38]
Change in Neuropsychiatric Inventory-Clinician rating scale (NPI-C) Core Caregiver Distress score [Time frame: Up to approximately Week 38]
Number of participants with Adverse Events (AEs) [Time frame: Up to approximately Week 42]
Number of participants with Treatment Emergent Adverse Events (TEAEs) [Time frame: Up to approximately Week 42]
Number of participants with Serious Adverse Events (SAEs) [Time frame: Up to approximately Week 42]
Number of participants with TEAEs leading to study withdrawal [Time frame: Up to approximately Week 42]
Number of participants with AEs including procholinergic and anticholinergic symptoms [Time frame: Up to approximately Week 42]
Number of participants with Adverse Events of Special Interest (AESIs) [Time frame: Up to approximately Week 42]
Barnes Akathisia Rating Scale (BARS) [Time frame: Up to approximately Week 38]
Abnormal Involuntary Movement Scale (AIMS) [Time frame: Up to approximately Week 38]
Body weight [Time frame: Up to approximately Week 38]
BMI [Time frame: Up to approximately Week 38]

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:

Serum prostate specific antigen (PSA) > 10 ng/mL at Screening
An 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 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Single group
Masking: Quadruple blind
Primary purpose: Treatment