A PHASE 1B DOSE RANGE FINDING STUDY OF PHENSERINE COMPARED TO DONEPEZIL IN PARTICIPANTS WITH EARLY OR MILD ALZHEIMER’S DISEASE

Who can take part

• A diagnosis of AD based on the most recent NIA-AA diagnostic criteria for AD
• Capable of participating in all scheduled evaluations and complete all required tests
• Females of childbearing potential and males must commit to use highly effective methods of birth control from signing informed consent form until at least 30 days after last administration of phenserine or donepezil
• A significant change on a validated AD amyloid or tau biomarker (as determined either by visual reading of amyloid PET scans [using any of the approved ligands], or CSF Aβ 1-42 or blood p-tau 217 levels [cut-off as determined by the individual laboratory])
• MCI (FDA stage 3) or mild dementia (FDA stage 4) based on a CDR Global rating of 0.5 (MCI) or 1.0 (mild dementia)
• An MRI scan within the past two years that has no findings inconsistent with AD
• Participants who have recently participated in other clinical trials or have been under treatment with memantine or acetylcholinesterase inhibitors (e.g., Donepezil, Rivastigmine, Galantamine) must undergo a washout period of at least 4 weeks prior to the start of the study
• Capacity to give informed consent based on the clinical judgement of an experienced clinician
• The participant has an individual who is in regular contact via phone or in-person visits and who can act as a reliable study partner and provide meaningful input into rating scales
• Age ≥50 years
• Fluency in Norwegian and evidence of adequate premorbid intellectual functioning

Who cannot take part

• Participants using sedating drugs, if unavoidable, will be excluded from the study. However, short-acting sleep medications can be used if taken as recommended and if the participant has maintained a stable regimen for at least 3 months prior to the start of the study
• Current participation in any other drug trial(s)
• Current treatment with a cholinesterase inhibitor or memantine
• Participants undergoing or planning procedures requiring anesthesia with depolarizing neuromuscular blockers (e.g., succinylcholine) due to the risk of prolonged paralysis or apnea when combined with AChE inhibitors
• Significant cerebrovascular disease, as indicated by clinical history, neurological examination, or on MRI (including cortical infarction or deep white matter or periventricular white matter hyperintensities with a Fazekas scale score of 3
• Currently ongoing life-threatening disease, such as metastatic cancer, advanced cardiovascular disease, advanced respiratory disease, terminal kidney disease, or advanced stages of an infectious disease
• Any current or past neurological disease unrelated to AD and with cognitive sequelae
• Hypersensitivity to AChE inhibitors or related compounds: Known hypersensitivity to donepezil, piperidine derivatives, or any formulation components
• Active peptic ulcer disease or gastrointestinal bleeding, or a history of gastrointestinal ulcers or bleeding
• Severe cardiac conditions: Significant arrhythmias, sick sinus syndrome, supraventricular conduction abnormalities, or other cardiac rhythm disorders that could pose a risk with cholinesterase inhibitors
• Severe respiratory disease: Chronic obstructive pulmonary disease (COPD) or poorly controlled asthma
• History of urinary obstruction or bladder issues, particularly those requiring catheterization
• Current clinically significant depression or other mental disorders likely to affect cognition or interfere with study participation