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CompletedPhase 1 / PHASE2Results postedSafety, Tolerability, PK and PD of Posiphen® in Subjects With Early Alzheimer's Disease
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamic (PD) Effects of Posiphen® in Subjects With Early Alzheimer's Disease (AD)
Lead sponsor
Asset
Buntanetap
Listed sites
6
Recruiting sites
-
Enrollment
18
actual
Study population
Alzheimer’s disease
Key I/E criteria
•CDR global 0.5•MMSE 17-30•Study partner/caregiver required
Primary endpoints
•Safety and Tolerability of Multiple Ascending Doses of Posiphen•Levels of Posiphen and Its Metabolites•Fractional Synthesis Rate of Aβ40 in CSF
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. Male or female aged 55 to 89 years (inclusive), in good health, no frailty.
2. Female participants must be post-menopausal for at least 2 consecutive years or surgically sterile (bilateral tubal ligation, hysterectomy or bilateral oophorectomy) for at least 6 months prior to screening.
3. Female participants will be given a urine pregnancy test at the screening visit for which they should test negative.
4. Clinical profile consistent with MCI or mild AD, consistent with the core clinical criteria outlined in the NIA-AA Guidelines (2011).
5. MMSE score between 17 and 30 (inclusive).
6. CDR global score of 0.5 with a memory score of 0.5 or greater, or CDR global score of 1.0.
7. Participant likely to tolerate all study procedures per PI judgment.
8. To qualify for entry, subjects will have a CSF Abeta42-Abeta40 ratio below 0.131 that is consistent with Alzheimers disease as measured via mass spectrometry by C2N.
9. General cognition and functional performance sufficiently preserved that the subject can provide written informed consent.
10. A minimum of 6 years of education or good work history.
11. Study partner is available who has frequent contact with the subject (e.g., average of 10 hours per week or more), and can accompany the subject to most visits to answer questions about the subject. The study partner is required to attend the entire screening visit and the baseline visit. The study drug is dispensed to the participant at the baseline visit and the study partner (or other individual) should also oversee study drug administration if needed to ensure compliance with dose regimen. At a minimum, the study partner should stay for the first 3 hours of the confinement visit and return at the discharge to drive the subject home.
12. No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the Columbia Suicide Severity Rating Scale.
13. MRI scan within the 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. Lacunes that are not believed to contribute to the subjects cognitive impairment are permissible. If there is no MRI available within a 12-month timeframe, then an MRI must be performed as part of the screening procedures for eligibility.
14. Stability of permitted medications for 4 weeks prior to baseline. NOTE: Cholinesterase inhibitors and or memantine are allowable only if stable for 12 weeks prior to screen. If taking Arciept (donezepil), no more than 10 mg/day is permitted during the course of the study.
15. Adequate visual and hearing ability (physical ability to perform all the study assessments).
16. Good general health with no disease expected to interfere with the study. Subjects may have common age-related disorders (i.e., hypertension, type II diabetes, dyslipidemia, and hypothyroidism) as long as these disorders are being controlled by diet or medication.
17. Must speak English, Spanish, or Korean fluently
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 tricyclic antidepressant SSRI or SNRI medication at a stable dose is acceptable.
2. Other neurodegenerative diseases, including Parkinsons disease and Huntingtons disease, or cerebral tumor.
3. Dementia other than AD, such as Acquired Immunodeficiency Syndrome (AIDS), Creutzfeldt-Jakob disease (CJD), Lewy Bodies dementia (LBD), Cerebrovascular dementia (CVD), Progressive Supranuclear Palsy (PSP), or normal pressure hydrocephalus (NPH).
4. History of a seizure disorder.
5. Clinically significant abnormalities in screening laboratory or ECG results.
6. Has current serious or unstable illness including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that, in the investigators opinion, makes them ineligible for participation in this study.
7. Has four or more microinfarcts as noted in the MRI scan.
8. Has cancer or has had a malignant tumor within the past 3 years, except patients who underwent potentially curative therapy with no evidence of recurrence. (Patients with stable untreated prostate cancer or skin cancers are not excluded).
9. According to the criteria of the most current version of the DSM, alcohol abuse, alcohol dependence, or drug abuse in the past 5 years.
10. Participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 16 weeks prior to screening. (The end of a previous investigational trial is the date the last dose of an investigational agent was taken).
11. Resides in a skilled nursing facility.
12. Subjects with infection or inflammation of the skin or skin disease at or in proximity to the lumbar puncture site.
13. History of lumbar spine surgery or chronic low back pain (CLBP).
14. Subjects whom the site PI deems to be otherwise ineligible.
15. Has a deep brain stimulator (DBS).
Endpoints (22)
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
4 endpointsAssessment of Mental Status Effects
Time frame:MMSE was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.
Mini-Mental State Examination (MMSE)
concentration, descriptive
Assessment of Cognitive Effects
Time frame:ADAS-Cog12 was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, also allowing a +/- 2-day visit window.
ADAS-Cog
descriptive
Assessment of Mental Status Effects
Time frame:MMSE was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.
Mini-Mental State Examination (MMSE)
concentration, descriptive
Posted result
| Group | Value (mean), score on a scale | Standard deviation |
|---|---|---|
| Low Dosen=5 Participants | -1.4 | 0.89 |
| Medium Dosen=5 Participants | 1.2 | 2.39 |
| High Dosen=1 Participants | -1 | 0 |
| Placebon=7 Participants | 1.14 | 2.12 |
Assessment of Cognitive Effects
Time frame:ADAS-Cog12 was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, also allowing a +/- 2-day visit window.
ADAS-Cog
descriptive
Posted result
| Group | Value (mean), score on a scale | Standard deviation |
|---|---|---|
| Active Treatment Armsn=11 Participants | -0.55 | 6.04 |
| Placebo Armn=7 Participants | -1.57 | 5.19 |
Behavior / neuropsychiatric
2 endpointsAssessment of Neuropsychiatric Effects
Time frame:NPI was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.
Neuropsychiatric Inventory (NPI)
event count, event
Assessment of Neuropsychiatric Effects
Time frame:NPI was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.
Neuropsychiatric Inventory (NPI)
event count, event
Posted result
| Group | Value (mean), score on a scale | Standard deviation |
|---|---|---|
| Low Dosen=5 Participants | -2.6 | 2.88 |
| Medium Dosen=5 Participants | 3.4 | 8.47 |
| High Dosen=1 Participants | -9 | 0 |
| Placebon=7 Participants | -3.86 | 8.09 |
Amyloid biomarkers
4 endpointsFractional Synthesis Rate of Aβ40 in CSF Using the SILK™ Technique With Multiple Doses of Posiphen
Time frame:The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. CSF was collected between 6 and 16hrs during the confinement visit.
threshold achievement, improvement
Fractional Synthesis Rate of Aβ40 in CSF Using the SILK™ Technique With Multiple Doses of Posiphen
Time frame:The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. CSF was collected between 6 and 16hrs during the confinement visit.
threshold achievement, improvement
Posted result
| Group | Value (mean), fraction labeled:unlabeled Aβ40 per hr | Reported bounds |
|---|---|---|
| Low Dosen=4 Participants | 0.0405 | -0.0298 - 0.0431 |
| Medium Dosen=5 Participants | 0.0400 | -0.0373 - 0.0511 |
| High Dosen=1 Participants | 0.0206 | -0.0206 - 0.0206 |
| Placebon=5 Participants | 0.0375 | -0.0319 - 0.0449 |
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers
Time frame:CSF was sampled at Screening and at the start of the confinement visit, which occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.
descriptive
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers
Time frame:CSF was sampled at Screening and at the start of the confinement visit, which occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.
descriptive
Posted result
| Group | Value (least_squares_mean), ng/mL | Standard error |
|---|---|---|
| Active Treatment ArmsAβ38n=10 Participants | 0.391 | 0.173 |
| Aβ40n=10 Participants | 1.73 | 0.998 |
| Aβ42n=10 Participants | 0.107 | 0.0653 |
| sAPPαn=10 Participants | 6.49 | 5.75 |
| sAPPβn=10 Participants | 19.1 | 16.8 |
| Total Taun=10 Participants | 186.4 | 79.1 |
| Placebo ArmAβ38n=7 Participants | 0.593 | 0.199 |
| Aβ40n=7 Participants | 3.13 | 1.151 |
| Aβ42n=7 Participants | 0.211 | 0.0753 |
| sAPPαn=7 Participants | -3.5 | 9.07 |
| sAPPβn=7 Participants | -28.6 | 26.5 |
| Total Taun=7 Participants | 53.7 | 124.9 |
Fluid / digital biomarkers
8 endpointsThe Levels of Posiphen and Its Metabolites Will be Determined in Cerebrospinal Fluid (CSF)
Time frame:The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. Plasma was collected at 0, 2, 4, 8, 12, 16, 20, and 24hrs during the confinement visit.
concentration, descriptive
The Levels of Posiphen and Its Metabolites Will be Determined in Cerebrospinal Fluid (CSF)
Time frame:The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. Plasma was collected at 0, 2, 4, 8, 12, 16, 20, and 24hrs during the confinement visit.
concentration, descriptive
Posted result
| Group | Value (mean), ng/mL | Standard deviation |
|---|---|---|
| Low DosePosiphenn=5 Participants | 0.46 | 0.3 |
| N1 metaboliten=5 Participants | 0.02 | 0.04 |
| N8 metaboliten=5 Participants | 0.35 | 0.26 |
| Medium DosePosiphenn=5 Participants | 0.73 | 0.52 |
| N1 metaboliten=5 Participants | 0.28 | 0.3 |
| N8 metaboliten=5 Participants | 0.77 | 0.43 |
| High DosePosiphenn=1 Participants | 0.71 | 0 |
| N1 metaboliten=1 Participants | 0 | 0 |
| N8 metaboliten=1 Participants | 0.15 | 0 |
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Rates of Enrollment
Time frame:Up to 25 days
event count, event
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate %CSF Samples With Enough Volume for Testing
Time frame:Up to 25 days
descriptive
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction
Time frame:Up to 25 days
descriptive
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Rates of Enrollment
Time frame:Up to 25 days
event count, event
Posted result
| Group | Value (count_of_participants), Participants | Reported bounds |
|---|---|---|
| Active Treatment Armsn=11 Participants | 10 | - |
| Placebo Armn=7 Participants | 5 | - |
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate %CSF Samples With Enough Volume for Testing
Time frame:Up to 25 days
descriptive
Posted result
| Group | Value (number), percentage of CSF samples | Reported bounds |
|---|---|---|
| All Randomized Participants Who Completed 36 Hour Confinement Visit (n=15)n=15 Participants | 81.75 | - |
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction
Time frame:Up to 25 days
descriptive
Posted result
| Group | Value (number), percentage of participants | Reported bounds |
|---|---|---|
| All Randomized ParticipantsRated "Excellent" for quality of tests and attention received during participation in the study.n=15 Participants | 94 | - |
| Reported "Almost all of my expectations have been met" by the research program.n=15 Participants | 81 | - |
| Reported "Yes, definitely" they would recommend this research program to a friend.n=15 Participants | 94 | - |
| Reported "Yes, definitely" they would choose to participate again.n=15 Participants | 87.5 | - |
| Reported "Volunteering" as what they liked best about the study.n=15 Participants | 31 | - |
| Reported "Time Commitment" as what they liked least about the study.n=15 Participants | 31 | - |
| Reported "Yes", the 36 hour catheter procedure was done.n=15 Participants | 100 | - |
| Reported "No" adverse events were associated with the 36hr catheter procedure.n=15 Participants | 73 | - |
| Reported "Excellent" as the quality of the 36hr catheter procedure and attention they received.n=15 Participants | 80 | - |
| Reported the catheter procedure was "almost all of what I expected."n=15 Participants | 67 | - |
| Reported they liked best was "participating in cutting edge research and interacting with the team".n=15 Participants | 100 | - |
| Reported "Other" as what they liked least about the 36hr catheter procedure.n=15 Participants | 47 | - |
| Reported "Other" as what they would change about the 36hr catheter procedure.n=15 Participants | 71 | - |
| Reported they would change the number of visits.n=15 Participants | 50 | - |
Safety / tolerability / PK
2 endpointsSafety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations
Time frame:Up to 25 days
event count, event
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations
Time frame:Up to 25 days
event count, event
Posted result
| Group | Value (number), events | Reported bounds |
|---|---|---|
| Low DoseDefinitely Relatedn=5 Participants | 0 | - |
| Probably Relatedn=5 Participants | 0 | - |
| Possibly Relatedn=5 Participants | 1 | - |
| Unlikely Relatedn=5 Participants | 2 | - |
| Unrelatedn=5 Participants | 9 | - |
| Totaln=5 Participants | 12 | - |
| Medium DoseDefinitely Relatedn=5 Participants | 0 | - |
| Probably Relatedn=5 Participants | 1 | - |
| Possibly Relatedn=5 Participants | 0 | - |
| Unlikely Relatedn=5 Participants | 3 | - |
| Unrelatedn=5 Participants | 11 | - |
| Totaln=5 Participants | 15 | - |
| High DoseDefinitely Relatedn=1 Participants | 0 | - |
| Probably Relatedn=1 Participants | 0 | - |
| Possibly Relatedn=1 Participants | 0 | - |
| Unlikely Relatedn=1 Participants | 0 | - |
| Unrelatedn=1 Participants | 0 | - |
| Totaln=1 Participants | 0 | - |
| PlaceboDefinitely Relatedn=7 Participants | 0 | - |
| Probably Relatedn=7 Participants | 0 | - |
| Possibly Relatedn=7 Participants | 2 | - |
| Unlikely Relatedn=7 Participants | 2 | - |
| Unrelatedn=7 Participants | 6 | - |
| Totaln=7 Participants | 10 | - |
Other (unclassified)
2 endpointsThe Levels of Posiphen and Its Metabolites Will be Determined in Plasma
Time frame:The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. Plasma was collected at 0, 2, 4, 8, 12, 16, 20, and 24hrs during the confinement visit.
concentration, descriptive
The Levels of Posiphen and Its Metabolites Will be Determined in Plasma
Time frame:The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. Plasma was collected at 0, 2, 4, 8, 12, 16, 20, and 24hrs during the confinement visit.
concentration, descriptive
Posted result
| Group | Value (mean), ng/mL | Standard deviation |
|---|---|---|
| Low DosePosiphenn=5 Participants | 7.16 | 4.25 |
| N1 metaboliten=5 Participants | 1.29 | 0.77 |
| N8 metaboliten=5 Participants | 2.25 | 1.36 |
| Medium DosePosiphenn=5 Participants | 9.51 | 5.77 |
| N1 metaboliten=5 Participants | 3.02 | 1.4 |
| N8 metaboliten=5 Participants | 5.04 | 1.8 |
| High DosePosiphenn=1 Participants | 12.01 | 0 |
| N1 metaboliten=1 Participants | 2.51 | 0 |
| N8 metaboliten=1 Participants | 3.35 | 0 |
Publications (2)
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
- PMID38970127via DERIVED
- PMID38562783via DERIVED
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.