Psychosis Associated with Alzheimer’s Disease Dementia MedDRA version: 20.0 Level: PT Classification code 10012271 Term: Dementia Alzheimer's type System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10037234 Term: Psychosis System Organ Class: 100000004873
Conditions
Interventions
Product Name: KarXT
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Xanomeline Tartrate
CAS Number: 152854-19-8
Concentration unit: mg milligram(s)
Concentration type: not less then
Concentrat
Sponsors
Karuna Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is a male or female aged 55 to 90 years, inclusive, at Screening (Visit 1A) 2. Can understand the nature of the study and protocol requirements and provide a signed informed consent form (ICF) before any study assessments are performed. If local regulations do not allow electronic ICF, then paper ICFs are permitted. If the subject is deemed not competent to provide ICF, the following requirements for consent must be met. a. The subject’s legally acceptable representative (LAR) or caregiver/study partner, if local regulations allow, must provide ICF (paper or electronic) b. The subject must provide informed assent (paper or electronic) 3. Meets clinical criteria for the following disorders: a. Possible or probable AD 4. 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, e.g., major stroke, neoplasm, subdural hematoma. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening. (Note: If waiting for MRI or CT results, an extension [up to two weeks] of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor) 5. Living at the same home or residential assisted-living facility for a minimum of six weeks before Screening (Visit 1A) 6. 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: a. Attend all visits and report on subject’s status b. Oversee subject compliance with medication and study procedures c. Participate in the study assessments and provide informed consent (paper or electronic) to participate in the study 7. History of psychotic symptoms (meeting International Psychogeriatric Association [IPA] criteria [1]) for at least 2 months prior to Screening (Visit 1A). (Subjects may or may not have symptoms of agitation) 8. Clinical Global Impressions-Severity (CGI-S) scale with a score =4 (moderate) at Screening (Visit 1A). 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. 9. AD dementia subjects are required to meet at least one of the following criteria at Screening (Visit 1A): a. Moderate to severe delusions, defined as NPI-C: Delusions domain score of =2 on two of the eight items OR b. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of = 2 on two of the seven items. 10. MMSE score of 8 to 22, inclusive, at Screening (Visit 1A) 11. 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 (Visit 1A) and be willing to maintain a stable dose for the duration of the study. 12. 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 13. BMI must be within 18 to 40 kg/m2 14. 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 mat
Exclusion criteria
Exclusion criteria: 1. Psychotic symptoms that are primarily attributable to a condition other than the AD causing dementia e.g., schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features 2. History of major depressive episode with psychotic features during the 12 months prior to Screening (Visit 1A) 3. History of an axis I diagnosis of delirium, amnestic disorder, bipolar disorder, schizophrenia, or schizoaffective disorder 4. Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, 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 5. History of ischemic stroke within 12 months prior to Screening (Visit 1A) or any evidence of hemorrhagic stroke 6. History of cerebral amyloid angiopathy (CAA), epilepsy, central nervous system (CNS) neoplasm, unstable thyroid function, or unexplained syncope 7. Any of the following: a. New York Heart Association (NYHA) Class 2 congestive heart failure b. Grade 2 or greater angina pectoris c. Sustained ventricular tachycardia d. Ventricular fibrillation e. Torsade de pointes f. Implantable cardiac defibrillator 8. 8. Myocardial infarction within the 6 months prior to Screening (Visit 1A) 9. Personal or family history of symptoms of long QT syndrome as evaluated by the investigator 10. Human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or LFT results 11. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator 12. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months 13. Risk of suicidal behavior during the study as determined by the Investigator’s clinical assessment and/ or C-SSRS as confirmed by the following: a. Answers “Yes” on items 3, 4 or 5 (C-SSRS – ideation) with the most recent episode occurring within the 2 months before screening or, b. Answers “Yes” to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before screening 14. Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at Screening (Visit 1A) 15. Urine toxicology screen is positive for non-cannabis or non-benzodiazepine substances without the approval of the Medical Monitor 16. 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) a. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening (Visit 1A) may be permitted b. Mirtazapine may be used as a hypnotic if started at least 8 weeks prior to Screening (Visit 1A) If needed, an extension (up to two weeks) of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor. 17. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subj
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Visits 10-18;Main Objective: To evaluate relapse prevention in subjects with psychosis associated with AD dementia treated with KarXT compared to placebo;Secondary Objective: - To evaluate the time from randomization to discontinuation for any reason in subjects with psychosis associated with AD dementia treated with KarXT compared to placebo - To evaluate the safety and tolerability of KarXT compared to placebo;Primary end point(s): Time from randomization (end of Week 12; Visit 10) to relapse during the 26-week Double-Blind Randomized Withdrawal Treatment Period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time from randomization (end of Week 12; Visit 10) to discontinuation for any reason during the 26-week Double-Blind Randomized Withdrawal Treatment Period;Timepoint(s) of evaluation of this end point: Visits 10-18 | — |
Countries
Bulgaria, Chile, Croatia, Czechia, France, Germany, Italy, Serbia, Slovakia, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Karuna Therapeutics
Outcome results
None listed