Health Condition 1: G301- Alzheimers disease with late onset
Conditions
Interventions
Intervention1: Xanomeline or Trospium
Chloride Capsule: IMP Blinded.
2 Bottles in kit-
one bottle of
KarXT or PBO
and one of
KarX-EC or PBO.
Each container
will be labeled
per country
requireme
Sponsors
Bristol Myers Squibb India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Signed Written Informed Consent 1. Participants or their legally acceptable representative (LAR see APPENDIX 1) must be able and willing to sign and date an IRB or 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. Participant must be fluent in the language of the ICF to consent. Type of Participant and Target Disease Characteristics 2. A diagnosis of AD a) Clinical diagnosis as defined by mild (stage 4) or moderate (stage 5) AD dementia consistent with the NIA-AA core clinical criteria,15 AND b) in accordance with the 2024 NIA-AA criteria15 with one of the following confirmations of AD pathology - 1. Historical evidence of AD diagnosis with amyloid positron emission tomography (PET), Abeta42 by 40 ratio in CSF, pTau181 by Abeta42 ratio in CSF, or pTau217 by Abeta42 ratio in plasma using an assay that meets Health Authority requirements 2. If no historical evidence available or does not satisfy the above requirements - 1. A plasma biomarker will be assessed for eligibility and will meet regulatory requirements for intended use 2. If a plasma biomarker assay cannot be used or if the assay result is inconclusive or indeterminate, conduct one of the following- a. Amyloid PET b. Abeta42 per 40 ratio or pTau181 per Abeta42 ratio in CSF using an assay that meets Health Authority-requirements Note - As new CSF or plasma AD diagnostic biomarkers are accepted by regulatory authorities with an indication for diagnosis of AD and OR or as an aid in diagnosis of AD, the Sponsor will consider their inclusion. 3. BMI within 18 to 40 kg per sq m inclusive. 4. MMSE score of 12 through 22 inclusive, at screening. 5. Participant has a stable living environment for at least 6 weeks prior to screening. Participants are eligible if they are in nursing homes, assisted living facilities, memory care facilities, or living at home. 6. Capable of self-locomotion (alone or with the aid of an assistive device, wheelchairs and other mobility aids are acceptable) 7. 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. Age of Participant 8. Participant must be 60 to 85 years, inclusive, at the time of signing the ICF. Reproductive Status The investigator or designee shall counsel IOCBP participants (as defined in APPENDIX 3) and male (as assigned at birth) participants who are sexually active with IOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. Local laws and regulations may require the use of alternative and OR or additional contraceptive methods. 9. Female (as assigned at birth) participants who are not of childbearing potential (as defined in APPENDIX 3) must have documented proof. Documentation can be obtained from the site personnel s review of the participant s
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply - Psychiatric Conditions 1. Risk of suicidal behavior during the study as determined by the investigators clinical assessment and OR or C-SSRS (baseline version) as confirmed by the following - a) Answers Yes on items 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 2. Any current primary psychiatric diagnosis (eg, major depression, schizoaffective disorder, bipolar disorder) or severe psychiatric symptoms (eg, hallucination, agitation or delusions) if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of treatment effect, affect cognitive assessment, or may impact the participants ability to complete the study. 3. Participants with history of schizophrenia or other chronic psychosis. 4. Any prior or ongoing uncontrolled/unstable psychiatric disorder that could interfere with study assessments. Medical Conditions 5. History or presence of clinically significant cardiovascular (eg, untreated or unstable hypertension, clinically significant tachycardia), pulmonary, renal, hematologic, gastrointestinal (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. 6. History of ischemic stroke within 12 months prior to the screening visit, or any evidence of hemorrhagic stroke. 7. History of cerebral amyloid angiopathy, epilepsy, CNS neoplasm, unstable thyroid function, or unexplained syncope. 8. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma. 9. Active biliary disease (eg, symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the medical monitor. 10. Participants with any of the following: a) history of bladder stones b) history of recurrent urinary tract infections c) For male participants, serum prostate-specific antigen greater than 10 ng per mL at screening d) For male participants, an IPSS score of 5 (ie, almost always) on items 1, 3, 5, or 6 e) For male participants, an IPSS score greater than equal to 9 for the sum of items 1, 3, 5, and 6 11. All grades of hepatic impairment (mild [Child-Pugh Class A], moderate [Child-Pugh Class B], and severe [Child-Pugh Class C]). 12. Participants with HIV with detectible viral load, HCV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and OR or active hepatic viral infections based on either medical history or LFT results. 13. History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months. 14. History of allergy OR hypersensitivity to any component (including excipients) of the study intervention or related compounds. 15. History of cerebral amyloid angiopathy, epilepsy, CNS neoplasm, unstable thyroid function, or unexpla
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in ADAS-Cog11 at Week 24 CIBIC+ at Week 24Timepoint: Change from baseline in ADAS-Cog11 and CIBIC plus at Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in ADCS-ADL at Week 24 Change from baseline in NPI total score at Week 24Timepoint: 24 weeks; Occurence of AEs and SAEs, AESIs, AEs leading to study intervention discontinuation, AEs leading to study discontinuation, and AEs leading to death through Week 24 Incidence and severity of clinically significant changes in vital signs, ECG, C-SSRS, weight, and safety laboratory tests through Week 24 Timepoint: Week 24;- Change from baseline in EQ-5D-5L, EQ-VAS,and QoL-AD at Week 24 - Change from baseline in ZCI-AD-27 scores at Week 24 - Change from baseline in MMSE score at Week 24 - Plasma concentrations of xanomeline and trospium - Change from baseline in plasma AD markers (eg, total Tau, pTau181, pTau217, ABeta [1-42], ABeta [1-40], NfL, and GFAP)Timepoint: Week 24 | — |
Countries
India
Contacts
Public ContactKartik Doshi
Bristol Myers Squibb
Outcome results
None listed