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CTRI Number  CTRI/2025/11/097417 [Registered on: 13/11/2025] Trial Registered Prospectively
Last Modified On: 16/03/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   A Study to Evaluate KarXT as a Treatment for Psychosis Associated With Alzheimers Disease  
Scientific Title of Study   A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated with Alzheimer’s Disease (ADEPT-4) 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
2024-516363-92  EudraCT 
CN0120056 Protocol Amendment 02 Dated 24-Feb-2025  Protocol Number 
U1111-1310-4139  UTN 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Rashmi Chitgupi 
Designation  Country Head- Clinical Research Group 
Affiliation  PPD Pharmaceutical Development India Private Limited 
Address  102-A wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East

Mumbai
MAHARASHTRA
400099
India 
Phone  02266022900  
Fax    
Email  rashmi.chitgupi@thermofisher.com  
 
Details of Contact Person
Scientific Query  
Name  Rashmi Chitgupi 
Designation  Country Head- Clinical Research Group 
Affiliation  PPD Pharmaceutical Development India Private Limited 
Address  102-A wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East

Mumbai
MAHARASHTRA
400099
India 
Phone  02266022900  
Fax    
Email  rashmi.chitgupi@thermofisher.com  
 
Details of Contact Person
Public Query  
Name  Rashmi Chitgupi 
Designation  Country Head- Clinical Research Group 
Affiliation  PPD Pharmaceutical Development India Private Limited 
Address  102-A wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East

Mumbai
MAHARASHTRA
400099
India 
Phone  02266022900  
Fax    
Email  rashmi.chitgupi@thermofisher.com  
 
Source of Monetary or Material Support  
Karuna Therapeutics, Inc., a Bristol-Myers Squibb company 99 High Street, 26th Floor Boston, MA 02110  
 
Primary Sponsor  
Name  Karuna Therapeutics, Inc., a Bristol-Myers Squibb company 
Address  99 High Street, 26th Floor Boston, MA 02110 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Argentina
Belgium
Brazil
Bulgaria
Croatia
France
Germany
Greece
Hungary
Israel
Italy
Japan
Poland
Portugal
Republic of Korea
Romania
Serbia
Slovakia
Spain
Turkey
United States of America
India  
Sites of Study
Modification(s)  
No of Sites = 6  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Chandrasekhar Kammammettu  Asha Hospital  ROAD NO. 14, BANJARA HILLS, HYDERABAD, 500034, TELANGANA, INDIA
Hyderabad
TELANGANA 		 9866192374

kcsekhar56@yahoo.co.in 
Dr Shailesh Pangaonkar  Central Institute of Behavioural Science  Srividya,8, Nawab Layout, Tilak Nagar, Nagpur-440010, Maharashtra, India
Nagpur
MAHARASHTRA 		 9423105228

cibsindia2025@gmail.com 
Dr Venu Gopal Jhanwar  Deva Institute of Healthcare & Research Pvt. Ltd.  B 27/70 MN,Durgakund,Varanasi-221005 U.P. India
Varanasi
UTTAR PRADESH 		 9935571052

vgj.dihr@gmail.com 
Dr Hrishikesh Kumar  Institute of Neurosciences Kolkata  185/1, A.J.C Bose Road, Kolkata-700017
Kolkata
WEST BENGAL 		 9874645445

rishi_medicine@yahoo.com 
Dr Parth Singh Meena  Jawahar Lal Nehru Medical College  Jawahar Lal Nehru Medical College Kala Bagh, Ajmer, Rajasthan – 305001, India
Ajmer
RAJASTHAN 		 9414456991

doctor.parth@outlook.com 
Dr Aseem Mehra  Postgraduate Institute of Medical Education and Research  Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh – 160012, India
Chandigarh
CHANDIGARH 		 7087002714

aseemmehra86@gmail.com  
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 6  
Name of Committee  Approval Status 
DMHC Ethics Commiittee  Approved 
Ethics Committee Asha Hospital  Approved 
Institutional Ethics Committee Institute of Neurosciences  Approved 
Institutional Ethics Committee PGIMER  Approved 
Institutional Ethics Committee, Jawahar Lal Nehru Medical College  Approved 
Institutional Ethics Committee, Rughwani Child Care Centre and Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: F24||Shared psychotic disorder,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  KarXT  Dose strength: a. 20/2 mg TID (20 mg xanomeline/ 2 mg trospium) (total daily dose [TDD] 60/6 mg) b. 30/3 mg TID (30 mg xanomeline/ 3 mg trospium) (TDD 90/9 mg) c. 40/4 mg TID (40 mg xanomeline/4 mg trospium) (TDD 120/12 mg) d. 50/5 mg TID (50 mg xanomeline/5 mg trospium) (TDD 150/15 mg) e. 66.7/6.67 mg TID (66.7 mg xanomeline/6.67 mg trospium) (TDD 200/20 mg) Presentation: Capsule Route of Administration: Oral 
Comparator Agent  Placebo  Dose strength: NA Presentation: Capsule Route of Administration: Oral 
 
Inclusion Criteria
Modification(s)  
Age From  55.00 Year(s)
Age To  90.00 Year(s)
Gender  Both 
Details  Participants are eligible to be included in the study only if all the following criteria apply

Is a male or female aged 55 to 90 years inclusive at Screening Visit 1

Participants or their legally acceptable representative must have signed and dated an Institutional Review Board IRB Independent Ethics Committee IEC approved written informed consent form ICF in accordance with regulatory local and institutional guidelines

This ICF must be obtained before performing any protocol related procedures that are not part of normal patient care

If the participant is deemed not competent to provide IC the following requirements for consent must be met

The participant’s legally acceptable representative LAR must provide IC

The participant must provide informed assent

A diagnosis of AD in accordance with the 2024 National Institute on Aging and Alzheimer’s Association NIA AA criteria with one of the following confirmations of AD pathology
Historical evidence of AD diagnosis with amyloid positron emission tomography (PET), A beta 42/40 ratio in CSF, pTau181/A beta 42 ratio in CSF, or pTau217/A beta 42 ratio in plasma using an assay that meets Health Authority requirements
If no historical evidence is available or does not satisfy the above requirements:
A plasma biomarker will be assessed for eligibility and will meet regulatory
requirements for intended use.
If a plasma biomarker assay cannot be used or if the assay result is inconclusive,
conduct one of the following:
Amyloid PET
A beta 42/40 ratio or pTau181/A beta 42 ratio in CSF using an assay that meets Health
Authority-requirements
As new CSF or plasma AD diagnostic biomarkers are accepted by regulatory authorities with an indication for diagnosis of AD and/or as an aid in diagnosis of AD, the Sponsor will consider their inclusion.

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 eg major stroke neoplasm subdural hematoma

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 6 weeks before Screening Visit 1

Capable of self locomotion alone or with the aid of an assistive device and have an identified study partner who should have daily contact approximately 10 hours a week or more and is willing to

Attend all visits and report on participant’s status

Oversee participant compliance with medication and study procedures

Participate in the study assessments and provide IC to participate in the study

History of psychotic symptoms meeting International Psychogeriatric Association criteria for at least 2 months prior to Screening Visit 1 participants may or may not have symptoms of agitation

CGI S scale with a score greater than or equal to 4 moderate at Screening Visit 1 and at Visit 2

CGI S requires the assessor to consider aspects of the psychosis hallucinations and delusions prior to providing a global assessment of severity

AD participants are required to have NPI C H plus D score of greater than or equal to 6 AND meet at least one of the following criteria at Screening Visit 1 and Visit 2

Moderate to severe delusions defined as NPI C Delusions domain score of greater than or equal to 2 on 2 of the 8 items OR

Moderate to severe hallucinations defined as NPI C Hallucinations domain score of greater than or equal to 2 on 2 of the 7 items

MMSE score of 8 to 22 inclusive at Screening Visit 1

If the participant is taking a cholinesterase inhibitor and/or memantine they must have been on a stable dose for 6 weeks prior to Screening Visit 1 and willing to maintain a stable dose for the duration of the study

Participant 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/m to the ratio 2 inclusive

Female participants must not be pregnant or breastfeeding. Individuals of childbearing
potential (IOCBP), or male particpants whose sexual partners are 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 (eg, 30 days) after the last dose of IMP. Sperm donation is not allowed
for 30 days after the final dose of the IMP. A female participant is considered to be an IOCBP
after menarche and until she is in a postmenopausal state for 12 months or otherwise
permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). For the definition and list of highly effective methods of contraception 
 
ExclusionCriteria 
Details  Psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia eg schizophrenia schizoaffective disorder delusional disorder or mood disorder with psychotic features

History of major depressive episode with psychotic features during the 12 months prior to Screening Visit 1

History 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 participant ability to complete or comply with the study procedures or validity of the study results

Participants with any grade of hepatic impairment mild Child-Pugh Class A moderate Child-Pugh Class B and severe Child-Pugh Class C will be excluded

Significant and severe renal impairment based on a screening cutoff for estimated glomerular filtration rate of less than or equal to 50 mL per min

History of ischemic stroke within 12 months prior to Screening Visit 1 or any evidence of hemorrhagic stroke

History of cerebral amyloid angiopathy epilepsy CNS neoplasm current unstable thyroid function or unexplained syncope

Any of the following

New York Heart Association Class II or greater congestive heart failure

Grade 2 or greater angina pectoris

History of any of the following

Sustained ventricular tachycardia

Ventricular fibrillation

Torsades de pointes

Implantable cardiac defibrillator

Myocardial infarction within the 6 months prior to Screening (Visit 1)
Personal or family history of symptoms of long QT syndrome as evaluated by the
Investigator
Human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or LFT results
History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator
Male participants are excluded from the study if any of the following criteria apply:
i) History of bladder stones
ii) History of recurrent urinary tract infections
iii) Serum prostate specific antigen less than 10 ng/mL at Screening (Visit 1)
iv) An IPSS score of 5 (almost always) on items 1, 3, 5, or 6 (see Section 9.4.13)
v) A sum of scores on IPSS items 1, 3, 5, and 6 of greater than or equal to 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 the Investigator’s clinical
assessment and/or C-SSRS as confirmed by the following:
i) Answers “Yes” on items 3, 4, or 5 (C-SSRS – ideation) with the most recent episode
occurring within the 2 months before screening or,
ii) Answers “Yes” to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before Screening

Individuals who are breastfeeding
Prior exposure to KarXT

Unable to taper and discontinue a concomitant medication that would preclude participation in this study

History of receiving monoamine oxidase inhibitors, anticonvulsants mood stabilizers (eg, lithium), tricyclic antidepressants (eg, imipramine,
desipramine), or any other psychoactive medications except for as needed anxiolytics (eg,
lorazepam) within 6 weeks prior to Screening (Visit 1)


Experienced any significant AEs due to trospium, including a known hypersensitivity to
trospium


 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
1. To evaluate the efficacy of KarXT compared with
placebo in the treatment of psychosis in participants
with psychosis associated with AD as measured by
the Neuropsychiatric Inventory-Clinician (NPI-C):
Hallucinations and Delusions (H+D ) score

2. To evaluate the efficacy of KarXT compared with
placebo in the treatment of psychosis in participants
with psychosis associated with AD as measured by
the CGI-S scale: CGI-S requires the assessor to
consider aspects of the psychosis (hallucinations and delusions) prior to providing a global
assessment of severity. 		 1. Change from Baseline to end of Week 12 in NPIC:
H+D score

2. Change from Baseline to end of Week 12 in the
CGI-S score. 
 
Secondary Outcome  
Outcome  TimePoints 
To evaluate the efficacy of KarXT compared with placebo using the following:
-NPI-C Core score hallucinations, delusions, agitation, & aggression domains
-NPI-C Agitation score
-NPI-C Core Score Caregiver Distress scale (Hallucinations, Delusions, Agitation, & Aggression domains)
-Responder rate defining a responder as NPI-C H plus D score greater than or equal to 40 percent improvement
-CMAI-IPA score
-CMAI total score
 		 Change from Baseline to end of Week 12 in the-
-NPI-C Core score: Hallucinations, Delusions, Agitation, & Aggression domains
-NPI-C Agitation score
-NPI-C Core score Caregiver Distress scale (Hallucinations, Delusions, Agitation, & Aggression domains)

-Responder rate defined as NPI-C H plus D score greater than or equal to 40 percent improvement from Baseline to end of Week 12
-Change from Baseline to end of Week 12 in CMAIIPA score
-Change from Baseline to end of Week 12 in CMAI total score
 
 
Target Sample Size   Total Sample Size="366"
Sample Size from India="10" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   24/11/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  14/10/2024 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="0"
Months="5"
Days="15" 
Recruitment Status of Trial (Global)   Open to Recruitment 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of KarXT in adult participants who are aged 55 to 90 years and have mild to severe AD with moderate to severe psychosis related to AD. Participants may or may not have symptoms of agitation.
Approximately 406 participants will be enrolled to randomize approximately 366 participants (183 participants/arm). The study includes an up to 30-day Screening Period, a 2-week Placebo Run-In Period, a 12-week Randomized Treatment Period, and a Safety Follow-up visit following the end of treatment (EOT)/early termination (ET) if the participant does not enter a long-term open-label extension (OLE) safety study. The total study duration for an individual participant is approximately 22 weeks (Screening Period, Placebo Run-In Period, Randomized Treatment Period, and Safety Follow-up).
 
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