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A Dose-ranging Study to Investigate Efficacy of Buntanetap in Mild to Moderate AD
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study of Buntanetap in Participants With Mild to Moderate Alzheimer's Disease
Lead sponsor
Asset
Buntanetap
Listed sites
54
Recruiting sites
-
Enrollment
351
actual
Study population
Alzheimer’s disease
Key I/E criteria
•Alzheimer's disease•MMSE 14-24•Study partner/caregiver required
Primary endpoints
•ADAS-Cog•ADCS-CGIC
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
Timeline
Milestones
Assets
Drug assets
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Diagnosis of Alzheimer's disease according to National Institute on Aging and National Institute on Aging and Alzheimer's Association criteria for probable AD
2. Male or female aged 55 - 85 years.
3. MMSE 14-24.
4. Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week) and will accompany the participant to study visits at designated times.
5. Female participants of childbearing potential* must have a negative urine pregnancy test at Screening, must be non-lactating and must agree to use a highly effective method of contraception (i.e., a method resulting in a failure rate of less than 1% per year when used consistently and correctly) during the trial and for 4 weeks after the last dose of trial treatment, such as:
6. Male participants must be sterile or sexually inactive or agree not to father a child during the study and one month after the last dose of study medication and must agree to use a barrier method for contraception. Female partners of male subject must adopt a highly effective method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as:
7. Participants can provide written informed consent. If PI deems that participant cannot fully understand the consent form to give consent, their legally authorized representative (LARs) can provide written informed consent. Participants can comply with scheduled visits, and other study-related procedures to complete the study with the help of the study partner.
8. No evidence of current suicidal ideation or previous suicide attempt in the past 2 months as evaluated in the Columbia Suicide Severity Rating Scale nor suicidal behavior in the past 6 months as per investigator.
9. Stability of permitted medications for at least 4 weeks prior to screening.
1. Cholinesterase inhibitors and/or memantine medication
2. Anticonvulsant medications used for epilepsy or mood stabilization, neuropathic pain indications.
3. Mood-stabilizing psychotropic agents, including, but not limited to, lithium.
10. Adequate visual and hearing ability (physical ability to perform all the study assessments) as per investigator.
11. Good general health with no disease expected to interfere with the study as per investigator
Exclusion criteria
1. Has a history of a psychiatric disorder such as schizophrenia, bipolar disorder or major depression according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Mild depression or history of depression that is stable on treatment with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) medication at a stable dose is acceptable.
2. Has non-AD dementia, such as vascular dementia, Lewy body dementia, frontotemporal disease, Parkinson disease dementia, B12 and thyroid deficiency caused dementia.
3. History of a seizure disorder, if stable on medication is acceptable.
4. Has a history or current evidence of long QT syndrome, Fridericia's formula corrected QT (QTcF) interval ≥ 450 ms for men and 460 ms for women, or torsades de pointes.
5. Has bradycardia (<50 bpm) or tachycardia (>100 bpm) on the ECG at screening.
6. Has uncontrolled Type-1 or Type-2 diabetes. A subject with HbA1c levels up to 7.5% can be enrolled if the investigator believes the subject's diabetes is under control.
7. Has clinically significant renal (CKD-EPI with normal <60 mL/min/BSA (body surface area) or hepatic impairment (ALP > 2.0 ULN and/or total bilirubin > 2.0 ULN) .
8. Has any clinically significant abnormal laboratory values. Participants with liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) greater than twice the upper limit of normal will be excluded.
9. Is at imminent risk of self-harm, based on clinical interview and responses on the C SSRS, or of harm to others in the opinion of the Investigators. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or method (e. g. positive response to Items 4 or 5 in assessment of suicidal ideation on the C SSRS) in the past 2 months, or suicidal behavior in the past 6 months.
10. Has cancer or has had a malignant tumor within the past year, except participants who underwent potentially curative therapy with no evidence of recurrence. (Participants with stable untreated prostate cancer or skin cancers are not excluded).
11. Alcohol / Substance use disorder, moderate to severe, in the last 5 years according to the most current version DSM.
12. Participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 4 weeks prior to the start of screening, or five half-lives of the investigational drug, whichever is greater.
The end of a previous investigational trial is the date the last dose of an investigational agent was taken.
13. Participants with learning disability or developmental delay.
14. Participants whom the site PI deems to be otherwise ineligible.
15. Participants with a known allergy to the investigational drug or any of its components. Here are all the inactive ingredients of the investigational medicinal product:
16. Subject is currently pregnant, breast-feeding and/or lactating.
17. Subject is currently taking strong and moderate CYP3A4 inhibitors and/or inducers. (e.g., CYP3A4 inhibitors Itraconazole, Ketoconazole, Azamulin, Troleandomycin, Verapamil; CYP3A4 inducers Rifampicin)
Endpoints (9)
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
Global cognition
3 endpointsChange From Baseline to Week 12 in ADAS-Cog11
Time frame:Baseline to the end of treatment period (12 weeks)
ADAS-Cog
change from baseline, improvement
Change From Baseline to Week 12 in ADAS-Cog11
Time frame:Baseline to the end of treatment period (12 weeks)
ADAS-Cog
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), units on a scale | Standard error |
|---|---|---|
| Placebon=79 Participants | -2.32 | 0.533 |
| 7.5mg Buntanetap/Posiphenn=81 Participants | -1.34 | 0.526 |
| 15mg Buntanetap/Posiphenn=78 Participants | -3.01 | 0.534 |
| 30mg Buntanetap/Posiphenn=79 Participants | -2.24 | 0.531 |
Change From Baseline to Week 12 in ADAS-Cog11 for Biomarker Positive Participants With Baseline MMSE Scores 21-24
Time frame:Baseline to the end of treatment period (12 weeks)
ADAS-Cog
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), units on a scale | Standard error |
|---|---|---|
| Placebon=18 Participants | -0.26 | 0.911 |
| 7.5mg Buntanetap/Posiphenn=20 Participants | -2.19 | 0.865 |
| 15mg Buntanetap/Posiphenn=22 Participants | -2.79 | 0.815 |
| 30mg Buntanetap/Posiphenn=22 Participants | -3.32 | 0.820 |
Function / daily living
2 endpointsChange From Baseline to Week 12 in ADCS-ADL
Time frame:Baseline to end of treatment period (12 weeks)
ADCS-Activities of Daily Living (ADCS-ADL)
change from baseline, improvement
Change From Baseline to Week 12 in ADCS-ADL
Time frame:Baseline to end of treatment period (12 weeks)
ADCS-Activities of Daily Living (ADCS-ADL)
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), units on a scale | Standard error |
|---|---|---|
| Placebon=78 Participants | 2.03 | 0.811 |
| 7.5mg Buntanetap/Posiphenn=80 Participants | -0.14 | 0.806 |
| 15mg Buntanetap/Posiphenn=74 Participants | 1.71 | 0.831 |
| 30mg Buntanetap/Posiphenn=76 Participants | 0.15 | 0.822 |
Neurodegeneration biomarkers
2 endpointsChange From Baseline to Week 12 in Plasma Biomarkers
Time frame:Baseline to the end of treatment period (12 weeks)
Neurofilament light (NfL)
change from baseline, improvement
Change From Baseline to Week 12 in Plasma Biomarkers
Time frame:Baseline to the end of treatment period (12 weeks)
Neurofilament light (NfL)
change from baseline, improvement
Posted result
| Group | Value (mean), pg/ml | Standard deviation |
|---|---|---|
| PlaceboGFAPn=71 Participants | 5.5 | 74.32 |
| NFLn=71 Participants | 0.4 | 6.88 |
| TDP43n=61 Participants | -467.5 | 1474 |
| 30mg Buntanetap/PosiphenGFAPn=70 Participants | 2.1 | 69.44 |
| NFLn=70 Participants | -2.5 | 14.05 |
| TDP43n=65 Participants | -985.1 | 4950 |
Other clinical outcomes
2 endpointsADCS-CGIC at Week 12
Time frame:Baseline to the end of treatment period (12 weeks)
change from baseline, improvement
ADCS-CGIC at Week 12
Time frame:Baseline to the end of treatment period (12 weeks)
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Placebon=82 Participants | 3.58 | 0.129 |
| 7.5mg Buntanetap/Posiphenn=84 Participants | 3.96 | 0.128 |
| 15mg Buntanetap/Posiphenn=80 Participants | 3.61 | 0.131 |
| 30mg Buntanetap/Posiphenn=79 Participants | 3.83 | 0.132 |
Provenance
Sources
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.