Open-label Extension of KarXT and KarX EC for Agitation in Alzheimer Disease
Scientific Title of Study
A Phase 3, Open label Extension Study to Evaluate the Long term Safety and
Tolerability of KarXT and KarX EC for the Treatment of Agitation Associated with Alzheimer
Disease (ADAGIO 3)
Trial Acronym
ADAGIO 3
Secondary IDs if Any
Secondary ID
Identifier
2024-519994-20
EudraCT
CN012-0025 v 1.0 dated 24 Feb 2025
Protocol Number
U1111-1316-3903
UTN
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Shilpi Sinha
Designation
Director, RCO Head
Affiliation
Bristol Myers Squibb
Address
Bristol-Myers Squibb India Private Limited, One International Centre, 6th Floor, Tower 1,
Senapati Bapat Marg, Elphinstone (W), Mumbai- 400013
India Bristol-Myers Squibb India Private Limited
Mumbai MAHARASHTRA 400013 India
Phone
912266288600
Fax
Email
shilpi.sinha@bms.com
Details of Contact Person Scientific Query
Name
Dr Kartik Doshi
Designation
Associate Director, Medical Lead
Affiliation
Bristol Myers Squibb
Address
Bristol-Myers Squibb India Private Limited, One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai- 400013 Mumbai MAHARASHTRA 400013 India
Phone
02266288645
Fax
Email
kartik.doshi@bms.com
Details of Contact Person Public Query
Name
Shilpi Sinha
Designation
Director, RCO Head
Affiliation
Bristol Myers Squibb
Address
Bristol-Myers Squibb India Private Limited, One International Centre, 6th Floor, Tower 1,
Senapati Bapat Marg, Elphinstone (W), Mumbai- 400013
India
Mumbai MAHARASHTRA 400013 India
Phone
912266288600
Fax
Email
shilpi.sinha@bms.com
Source of Monetary or Material Support
BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED One International Center, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai- 400013 India
Primary Sponsor
Name
Bristol Myers Squibb India Private Limited
Address
One International Center, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai- 400013 India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Brazil Argentina Bulgaria Canada Chile Croatia Czech Republic France Germany Greece Hungary Israel Italy Japan Mexico Poland Portugal Republic of Korea Romania Spain Taiwan Ukraine United Kingdom United States of America India
Sites of Study
No of Sites = 7
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Vaibhav Patil
All India Institute of Medical Sciences
Department of Psychiatry
Room No. 4096, 4th Floor,
Academic Building, AIIMS,
Ansari Nagar, New Delhi 110029
India New Delhi DELHI
09968721083
drvaibhavp317@gmail.com
Dr Amitabha Ghosh
Apollo Multispeciality Hospitals Limited
Clinical Trial Department, Daycare Building, 6th Floor, Back Side, 58, Canal Circular Road, Kolkata Kolkata WEST BENGAL
9830119686
amitabhaghosh269@gmail.com
Dr G Prasad Rao
Asha Hospitals
Asha Hospital, Research Department Room No.: A4, A5, A6, 5th floor Road No.14, Banjara Hills, Hyderabad, Telangana-500034, India Hyderabad TELANGANA
9985900005
prasad40@gmail.com
Dr Venu Gopal Jhanwar
Deva Institute of Healthcare & Research (DIHR) Pvt Ltd
Research Wing, Dcap l"tFloor
Deva lnstitute of Healthcare & Research pvt.
Ltd.B27 170 MN, Durgakund, Varanasi-221 005
Uttar Pradesh, lndia Varanasi UTTAR PRADESH
09936611111
dihr.rw@gmail.com
Dr Pradhyuman Jeshingbhai Chaudhary
GMERS Medical College & Civil Hospital
Department of Psychiatry
101, First Floor, A-Block,
GMERS Medical College & Civil Hospital,
Sola, Nr Gujarat High Court, Ahmedabad-
380060, Gujarat, India Ahmadabad GUJARAT
09825411772
drpradhyuman@gmail.com
Dr Suman Kushwaha
Institute of Human Behavior & Allied Sciences
Department of Neurology
Room No.109 Academic Block
110095, Delhi, India New Delhi DELHI
09868396814
sumankushwaha@gmail.com
Dr Jaydip Ray Chaudhari
Yashoda Healthcare Services Private Limited
Department of Neurology Room No.108, 1st Floor Raj Bhavan Road, Somajiguda, Hyderabad, Telangana-500082 Hyderabad TELANGANA
09849007975
jaydiprc@gmail.com
Details of Ethics Committee
No of Ethics Committees= 7
Name of Committee
Approval Status
DMHC Ethics Commiittee, Deva Institute of Healthcare and Research P. Ltd. B 27/70 MN Durgakund Varanasi Uttar Pradesh - 221005
Institute Ethics Committee, All India Institute of Medical Sciences, Old OT Block, Room No. 102, AIIMS Hospital, Ansari Nagar, New Delhi-29 India
Submittted/Under Review
Institutional - Ethics Committee IHBAS Room No – 125 - 1st Floor, Academic Block, Institute of Human Behavior & Allied Sciences -110095, Delhi, India
Approved
Institutional Ethics Committee Apollo Gleneagles Hospital ,Kolkata Apollo Gleneagles Hospital 58 Canal Circular Road kolkata 700054
Approved
Institutional Ethics Committee, GMERS medical college, Sola Highway, Near Gujarat High court, Ahmedabad Gujarat - 380061 India
Submittted/Under Review
Yashoda Academy of Medical Education and Research Yashoda Hospitals Behind Hari Hara kala Bhawan SP Road Secunderabad, Hyderabad Telangana - 500003 India
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: G301||Alzheimers disease with late onset,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Drug or Xanomeline Enteric Capsule
KarX-EC BMS986519 - 2 Bottles (KarXTor PBO and KarX-EC or PBO) will be packaged in kits. Each container will be labeled as required per country requirement. Dose - 14 mg, 28 mg, 42 mg, 56 mg Route of administration - Oral Frequency - BID Duration of intervention - 14 weeks
Intervention
Drug or Xanomeline or Troposium Chloride capsule
KarXT BMS-986510. 2 Bottles (KarXTor PBO and KarX-ECor PBO) will be packaged in kits. Each container will be labeled as required per country requirement Dose - 14 mg/3mg, 28 mg/6mg, 42 mg/9mg, 56 mg/12mg, Route of administration - Oral Frequency - BID Total duration of intervention - 14 weeks
Comparator Agent
Placebo for KarXT + KarX-EC BID
Take dose twice daily (BID), Route of administration - Oral Total Duration of intervention - 14 weeks.
Inclusion Criteria
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 of the following criteria apply -
1)Participants must have completed study CN0120023 or CN0120024per protocol.
Signed Written Informed Consent
2)Participants (or their LAR, see APPENDIX 1) must have signed and dated an IRB or IEC-approved written 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 participant
should provide informed assent, if required by local regulations.
3)Have one identified caregiver who should have sufficient contact (approximately 10 hours a
week or more) and is willing to:
- Attend all visits and report on participants status
- Oversee participant compliance with medication and study procedures
- Participate in the study assessments and provide IC to participate in the study
- The caregiver role in non-institutionalized settings may or may not be the same individual
who fulfills the role of caretaker. In institutionalized settings (eg, nursing homes or
memory care facilities), a caregiver may be a staff member of the institutionalized setting
or another individual (eg, family member, family friend, hired professional caregiver) who
fulfills the above criteria.
ExclusionCriteria
Details
Participants are excludedfrom the study if any of the following criteria apply-
Medical Conditions
1)History or presence (including those that could have developed during study CN0120023 or
CN0120024) of clinically significant cardiovascular (eg, untreated or unstable hypertension,
clinically significant tachycardia), pulmonary, renal, hematologic, GI,eg, obstructive
disorders (including conditions that may decrease GI motility, such as ulcerative colitis,
intestinal atony, and myasthenia gravis), endocrine, immunologic, dermatologic, neurologic,or oncologic disease or any other condition that, in the opinion of the investigator, would
jeopardize the safety of the participant or the validity of the study results.
2)All grades of hepatic impairment (mild [Child-Pugh Class A), moderate(Child-Pugh Class
B), and severe (Child-Pugh Class C)).
3)If, in the opinion of the Investigator and or Sponsor OR Medical Monitor, participant is unsuitable
for enrollment in the study or participant has any finding that, in the view of the Investigator
and OR or Sponsor OR Medical Monitor, may compromise the safety of the participant or affect
his or her ability to adhere to the protocol visit schedule or fulfill visit requirements.
4)Risk of suicidal behavior during the study as determined by the Investigators clinical
assessment and OR 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
Physical and Laboratory Test Findings
5)An eGFR of less than or equal to 50mL per min at screening.
6)Elevations in hepatic transaminases at screening greater than or equal to 2× ULN for ALT and AST
7)Bilirubin greater than 2× ULN, unless in the context of Gilberts syndrome.
8)History of unstable hypertension or tachycardia as evidenced by-
i)Blood pressure of greater than or equal to 160 or 100 mmHg (average of triplicate seated measures) at screening
ii)Heart rate of greater than or equal to 100 bpm (average of triplicate seated measures) at screening
9)Urine toxicology screen positive for phencyclidine, amphetamines, opiates, cocaine, or
alcohol (clinically significant alcohol use in the opinion of the Investigator)
10)Clinically significant abnormal finding on the physical examination, medical history, ECG
(QTcF of greater than 450 msec in males and greater than 470 msec in females), or clinical laboratory results at
Screening.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Incidence of any TEAEs
26 weeks
Secondary Outcome
Outcome
TimePoints
Reported AEs, TEAEs, SAEs, TEAEs leading to study
withdrawal and deaths
26 weeks
AESI
26 weeks
BARS and AIMS
26 weeks
Body weight and BMI
26 weeks
Orthostatic vital signs (supine and standing OR sitting
and standing after 2 minutes): blood pressure (systolic
and diastolic) and heart rate
26 weeks
Clinical laboratory evaluations
26 weeks
12-lead ECG
26 weeks
Suicidal ideation assessed using the C-SSRS
26 weeks
Assessment of cognition as measured by MMSE and
ADAS-Cog-13
26 weeks
Assessment of severity of benign prostatic hyperplasia
as measured by IPSS in male participant
26 weeks
Mean change from baseline to the end of Week 26 of EOT
on -
- CMAI-IPA, CMAI total score,CMAI domain
scores individually, CMAI Factor scores
individually
- CGI-S as it relates specifically to agitation in
Alzheimers disease
- NPI or NPI-NH Total and Domain Scores (individual
domain scores - Hallucinations, Delusions,
Agitation or Aggression, Depression or Dysphoria,
Anxiety, Elation or Euphoria, Apathy or Indifference,
Disinhibition, Irritability or Lability, Aberrant Motor
Behavior)
- NPI or NPI-NH Caregiver Distress or Occupational
Disruptiveness Scale
- ZCI-AD-27 Total Score
- QoL-AD Total Score
26 weeks
Change from baseline for biomarkers of
neurodegeneration and neuroinflammation over the
treatment period
Target Sample Size
Total Sample Size="600" Sample Size from India="17" 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)
21/07/2026
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
12/12/2025
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="7" Days="0"
Recruitment Status of Trial (Global)
Not Yet Recruiting
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 - YES
What data in particular will be shared? Response - All of the individual participant data collected during the trial, after de-identification.
What additional supporting information will be shared? Response - Study Protocol Response - Statistical Analysis Plan Response - Clinical Study Report
Who will be able to view these files? Response (Others) - None
For what types of analyses will this data be available? Response - To achieve aims in the approved proposal.
By what mechanism will data be made available? Response (Others) - To the regulatory agency
For how long will this data be available start date provided 10-08-2029 and end date provided 10-08-2044? Response (Others) - Immediately following publication. No end date.
Any URL or additional information regarding plan/policy for sharing IPD? Additional Information - NIL
Brief Summary
The primary objective of this OLEstudy isto evaluate thelong-termsafety and tolerability of
KarXT+ KarX-EC in the treatment of participants with agitation associated with AD.
Study Duration: maximum duration after screening for each participant will be 30 weeks.
Study Intervention Duration - The study includes up to a 26-weekopen-label treatment period and