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PATH-1

CompletedPhase 1

Phenserine on the Alzheimer's Treatment Horizon, Study 1

A Phase 1b Dose Range Finding Study of Phenserine Compared to Donepezil in Participants With Early or Mild Alzheimer's Disease

Lead sponsor

Helse Stavanger HF

Assets

Donepezil / Phenserine

Listed sites

1

Recruiting sites

-

Enrollment

16

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•CDR global 0.5•Study partner/caregiver required

Primary endpoints

•Panel 1•Panel 2•Panel 3

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDEuCT: 2023-510282-10-00
NCT IDNCT06774261

Timeline

Milestones

Study first posted2025-01-14actual
Study start2025-02-01actual
Primary completion2025-12-01actual
Study completion2025-12-08actual
Last update posted2026-05-04actual

Assets

Drug assets

DonepezilPhenserine

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age50 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

•A diagnosis of AD based on the most recent NIA-AA diagnostic criteria for AD.
•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.
•A CDR Global rating of 0.5 or 1.0.
•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, daily 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.
•Capable of participating in all scheduled evaluations and complete all required tests.
•Female participants must be of non-childbearing potential or have a negative serum pregnancy test up to 24 hours prior to the baseline assessments and agree to use effective birth control throughout their participation in the study from signing informed consent form until at least 30 days after last administration of phenserine or donepezil.

Exclusion criteria

•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 (25).
•Current treatment with a cholinesterase inhibitor or memantine.
•Hypersensitivity to AChE inhibitors or related compounds: Known hypersensitivity to donepezil, piperidine derivatives, or any formulation components.
•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.
•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.
•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).
•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.

Endpoints (30)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK
16
Other (unclassified)
4
Amyloid biomarkers
2
Tau biomarkers
2
Neurodegeneration biomarkers
2
Global cognition
1
Memory
1
Behavior / neuropsychiatric
1
Other clinical outcomes
1

Global cognition

1 endpoint
Other/protocol endpoint

Montreal Cognitive Assessment (MoCA)

Time frame:At baseline and end of treatment at 8 weeks.

Montreal Cognitive Assessment (MoCA)

descriptive

Memory

1 endpoint
Other/protocol endpoint

FLAME computer-based domain composites

Time frame:At baseline and end of treatment at 8 weeks

descriptive

Behavior / neuropsychiatric

1 endpoint
Secondary/protocol endpoint

Columbia Suicide Severity Rating Scale (C-SSRS) (Safety Assessment)

Time frame:At enrollment, week 4 and of treatment at 8 weeks.

descriptive

Amyloid biomarkers

2 endpoints
Primary/protocol endpoint

Panel 4: Concentration of Exosome-Derived Alzheimer's Disease-Specific Biomarkers

Time frame:From enrollment to the end of treatment at 8 weeks.

concentration, descriptive

Other/protocol endpoint

Cerebrospinal Fluid (CSF) Levels of Aβ1-40 and Aβ1-42

Time frame:Baseline and end of treatment at 8 weeks.

descriptive

Tau biomarkers

2 endpoints
Other/protocol endpoint

Cerebrospinal Fluid (CSF) Levels of Total Tau (tTau) and Phosphorylated Tau (pTau)

Time frame:Baseline and end of treatment at 8 weeks.

descriptive

Other/protocol endpoint

Plasma Levels of pTau217

Time frame:Baseline and end of treatment at 8 weeks.

Phosphorylated tau 217 (p-tau217)

descriptive

Neurodegeneration biomarkers

2 endpoints
Primary/protocol endpoint

Panel 2: Concentration of Synaptic Integrity Biomarkers

Time frame:From enrollment to the end of treatment at 8 weeks.

concentration, descriptive

Other/protocol endpoint

Plasma Levels of Neurofilament Light Chain (NfL)

Time frame:Baseline and end of treatment at 8 weeks.

Neurofilament light (NfL)

ratio, descriptive

Safety / tolerability / PK

16 endpoints
Secondary/protocol endpoint

Adverse Events (AEs) and Tolerability Profile

Time frame:From enrollment to the end of treatment at 8 weeks.

event count, event

Secondary/protocol endpoint

Blood Pressure (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks

descriptive

Secondary/protocol endpoint

Pulse (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

event count, event

Secondary/protocol endpoint

Urine Testing (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Blood Urea Nitrogen (BUN) (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Potassium (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Sodium (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Calcium (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Glucose (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Creatinine (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Total and Direct Bilirubin (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

C-Reactive Protein (CRP) (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Liver function (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Electrocardiogram (ECG) (Safety Assessment)

Time frame:From enrollment to the end of treatment at 8 weeks.

descriptive

Secondary/protocol endpoint

Maximum Plasma Concentration (Cmax) of Phenserine

Time frame:Measured at week 2, week 4, week 6 and of treatment at 8 weeks.

concentration, descriptive

Secondary/protocol endpoint

Half-Life (t1/2) of Phenserine and Donepezil

Time frame:Measured at week 2, week 4, week 6 and of treatment at 8 weeks.

concentration, descriptive

Other clinical outcomes

1 endpoint
Primary/protocol endpoint

Panel 1: Concentration of Biomarkers Associated with Preprogrammed Cell Death (PNCDD)

Time frame:From enrollment to the end of treatment at 8 weeks.

concentration, descriptive

Other (unclassified)

4 endpoints
Primary/protocol endpoint/low confidence

Panel 3: Concentration of TNF-α (Inflammatory Biomarker)

Time frame:From enrollment to the end of treatment at 8 weeks.

concentration, descriptive

Primary/protocol endpoint/low confidence

Panel 3: Concentration of interleukins, IL-1β, IL-6, and IL-10. (Inflammatory Biomarker)

Time frame:From enrollment to the end of treatment at 8 weeks.

concentration, descriptive

Secondary/protocol endpoint/low confidence

Cholinesterase Inhibition Target Achievement

Time frame:From enrollment to the end of treatment at 8 weeks.

time to event, event

Secondary/protocol endpoint/low confidence

Steady-State Concentration of Phenserine and Donepezil

Time frame:Measured at week 2, week 4, week 6 and of treatment at 8 weeks.

concentration, descriptive

Publications (12)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.