Health Condition 1: G301- Alzheimers disease with late onset
Conditions
Interventions
Intervention1: 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 requi
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 - 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.
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of any TEAEsTimepoint: 26 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Reported AEs, TEAEs, SAEs, TEAEs leading to study withdrawal and deathsTimepoint: 26 weeks;AESITimepoint: 26 weeks;BARS and AIMSTimepoint: 26 weeks;Body weight and BMITimepoint: 26 weeks;Orthostatic vital signs (supine and standing OR sitting and standing after 2 minutes): blood pressure (systolic and diastolic) and heart rateTimepoint: 26 weeks;Clinical laboratory evaluationsTimepoint: 26 weeks;12-lead ECGTimepoint: 26 weeks;Suicidal ideation assessed using the C-SSRSTimepoint: 26 weeks;Assessment of cognition as measured by MMSE and ADAS-Cog-13 Timepoint: 26 weeks;Assessment of severity of benign prostatic hyperplasia as measured by IPSS in male participantTimepoint: 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 ScoreTimepoint: 26 weeks;Change from baseline for biomarkers of neurodegeneration and neuroinflammation over the treatment periodTimepoint: | — |
Countries
Argentina, Brazil, Bulgaria, Canada, Chile, Croatia, Czech Republic, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Mexico, Poland, Portugal, Republic of Korea, Romania, Spain, Taiwan, Ukraine, United Kingdom, United States of America
Contacts
Public ContactShilpi Sinha
Bristol Myers Squibb
Outcome results
None listed