Alzheimer's DiseasePhase 1/2DISCOVERNCT02925650
Safety, Tolerability, PK and PD of Posiphen® in Subjects With Early Alzheimer's Disease
A Phase 1/2 study testing Posiphen in people with Alzheimer's Disease, run by Annovis Bio Inc. at 6 sites in United States.
Trial summary
This study evaluates the safety and pharmacological effects of 3 different doses of Posiphen® when compared to a placebo, in adult male and female patients with early Alzheimer's disease (AD). Read more about this study
- Who is it for?
- Ages 55 to 89 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Posiphen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 6 sitesUnited States
- Study dates
- 2 Mar 2017to 31 Dec 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged 55 to 89 years (inclusive), in good health, no frailty.
- 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.
- Female participants will be given a urine pregnancy test at the screening visit for which they should test negative.
- Clinical profile consistent with MCI or mild AD, consistent with the core clinical criteria outlined in the NIA-AA Guidelines (2011).
- MMSE score between 17 and 30 (inclusive).
- CDR global score of 0.5 with a memory score of 0.5 or greater, or CDR global score of 1.0.
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- Participant likely to tolerate all study procedures per PI judgment.
- 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.
- General cognition and functional performance sufficiently preserved that the subject can provide written informed consent.
- A minimum of 6 years of education or good work history.
- 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.
- No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the Columbia Suicide Severity Rating Scale.
- 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.
- 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.
- Adequate visual and hearing ability (physical ability to perform all the study assessments).
- 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.
- Must speak English, Spanish, or Korean fluently.
Who cannot join
- 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.
- Other neurodegenerative diseases, including Parkinsons disease and Huntingtons disease, or cerebral tumor.
- 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).
- History of a seizure disorder.
- Clinically significant abnormalities in screening laboratory or ECG results.
- 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.
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- Has four or more microinfarcts as noted in the MRI scan.
- 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).
- According to the criteria of the most current version of the DSM, alcohol abuse, alcohol dependence, or drug abuse in the past 5 years.
- 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).
- Resides in a skilled nursing facility.
- Subjects with infection or inflammation of the skin or skin disease at or in proximity to the lumbar puncture site.
- History of lumbar spine surgery or chronic low back pain (CLBP).
- Subjects whom the site PI deems to be otherwise ineligible.
- Has a deep brain stimulator (DBS).
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Washington University Sleep Medicine Center
Brentwood, Missouri, 63144
Cleveland Clinic
Cleveland, Ohio, 44195
IU Health Partners, Adult Neurology Clinic
Indianapolis, Indiana, 46202
UCSD Alzheimer's Disease Research Center
La Jolla, California, 92037
Columbia University Medical Center Sergievsky Center Taub Institute
New York, New York, 10032
About this study
Official title: 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)
This study evaluates the safety and pharmacological effects of 3 different doses of Posiphen® when compared to a placebo, in adult male and female patients with early Alzheimer's disease (AD).
Read the detailed description
Posiphen®, which was discovered by the US National Institute on Aging (NIA) is a small, orally active, experimental drug that specifically inhibits the synthesis of amyloid precursor protein (APP), Tau and α-Synuclein. It is distinct from other Alzheimer's disease drugs currently in development, because it inhibits the formation of several toxic proteins, rather than removing individual toxic protein after they are produced. Posiphen has potential utility as a disease modifying treatment for AD. The present study will confirm the pharmacokinetics (PK) of Posiphen and its metabolites in plasma and cerebral spinal fluid (CSF). It will also measure the effects of a 23-25 day treatment period with Posiphen on the CSF and plasma levels of a number of biomarkers, inflammatory factors and control proteins. It will also expand the safety data in humans by extending the treatment period from 10 days to a treatment period from 23-25 days. In addition, this study will measure concentrations of various soluble biomarkers in CSF and use the SILK™ assay methods to directly measure the effect of Posiphen on the fractional synthesis rate of Aβ40 in CSF, which will help guide the further development of Posiphen and determine the feasibility of SILK™ in a multicenter trial.
- Conditions
- Alzheimer's Disease
- Being tested
- Posiphen, Placebo
- Keywords
- Alzheimer's Disease, SILK™, Pharmacodynamics, Safety, Pharmacokinetics
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PosiphenDrug
oral solid dosage form capsule
PlaceboDrug
oral solid dosage form capsule
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Receives: Drug: Posiphen |
| Medium Dose | Experimental | The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Receives: Drug: Posiphen |
| High Dose | Experimental | The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Receives: Drug: Posiphen |
| Placebo | Placebo comparator | The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations
Number of adverse events or study discontinuations, broken down by dose arm (i.e. Low vs. Medium vs. High vs. Placebo), and further broken down by relatedness to Posiphen (Definitely Related, Probably Related, Possibly Related, Unlikely Related, Unrelated)
Measured: Up to 25 days
The Levels of Posiphen and Its Metabolites Will be Determined in Plasma
Mean plasma concentrations of levels of posiphen tartrate, N1 desmethyl posiphen, and N8 desmethyl Posiphen metabolite were determined for each of the three dose cohorts (Low Dose, Medium Dose, High Dose) by a protein precipitation extraction method using a high performance liquid chromatographic mass spectrometric detection method, with a linear weighted regression to determine their concentrations.
Measured: 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.
The Levels of Posiphen and Its Metabolites Will be Determined in Cerebrospinal Fluid (CSF)
Mean CSF concentrations of levels of posiphen tartrate, N1 desmethyl posiphen, and N8 desmethyl Posiphen metabolite were determined for each of the three dose cohorts (Low Dose, Medium Dose, High Dose) by a protein precipitation extraction method using a high performance liquid chromatographic mass spectrometric detection method, with a linear weighted regression to determine the concentrations.
Measured: 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.
Fractional Synthesis Rate of Aβ40 in CSF Using the SILK™ Technique With Multiple Doses of Posiphen
The fractional synthesis rate (FSR) of Aβ40 was measured in the CSF using the SILK™ technique. FSR is a measure of the rate of Aβ synthesis in the brain. During 13C6-leucine infusion, 13C6-leucine is incorporated into newly synthesized proteins throughout the body, including the brain, in proportion to the available 13C6-leucine. This FSR is calculated as the rate of change of the ratio of 13C6-leucine-labeled Aβ proteins to unlabeled Aβ proteins in the lumbar CSF between 6 to 16 hours, normalized to the ratio of labeled to unlabeled leucine amino acid in plasma. It is reported as a fraction of 13C6-leucine-labeled to unlabeled Aβ proteins per hour. The ratio of Aβ in CSF containing 13C6-leucine to that containing unlabeled leucine is measured using mass spectrometry.
Measured: 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.
Secondary outcomes (7)
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Rates of Enrollment
Feasibility of CSF Catheter Study with SILK™ Technology was determined by comparing the total number of participants enrolled, randomized and treated with study drug in the trial to the total number of participants who completed the CSF Catheter Study across all participating sites.
Measured: Up to 25 days
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate %CSF Samples With Enough Volume for Testing
The % of cerebrospinal fluid samples with sufficient volume for testing will be determined across study participants during the SILK sampling procedure
Measured: Up to 25 days
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction
Research satisfaction will be evaluated by qualitative response to 14 questions asked to participants about their experience with the study procedures. Responses will be grouped and reported by common themes
Measured: Up to 25 days
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers
Aβ38, Aβ40, Aβ42, sAPPα, sAPPβ, and T-Tau were sampled at Screening and at the start of the confinement visit. Results of these measures were reported as a least square means, calculated as the change between the measured values at the start of the confinement visit and Screening in ng/mL.
Measured: 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.
Assessment of Mental Status Effects
The short-term effects of Posiphen on mental status will be measured using the Mini-Mental State Examination (MMSE). The MMSE is a brief, global cognitive measure that includes orientation, memory, attention, concentration, naming, writing, repetition, comprehension, and construction. The total score ranges from 0 (worst) to 30 (best performance). Results of the MMSE for this trial were reported as a raw change score, calculated as the change between the total scores at two evaluation time points (Baseline, Pre-Confinement Visit) and where negative values are worse and positive values are better.
Measured: 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.
Assessment of Neuropsychiatric Effects
The Neuropsychiatric Inventory (NPI) was used to measure the frequency and severity of neuropsychiatric symptoms. On this scale frequency ratings range from 0 (no symptoms) to 4 (very frequently, once or more per day or continuously). Severity ratings range from 0 (no severity) to 3 (severe). The score for each of 12 symptoms measured in the scale is the product of severity and frequency within that symptom. The total score for the NPI is the sum of all 12 symptom item scores, for a highest possible total score of 144 in individuals with maximal symptoms, and a lowest possible total score of zero (0) in fully asymptomatic individuals. Lower scores are better and higher scores indicate more neuropsychiatric symptoms. Results are calculated as the change between the total scores at two evaluation time points (Baseline, Pre-Confinement Visit) with negative scores being better and positive scores being worse.
Measured: 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.
Assessment of Cognitive Effects
The short-term effects of Posiphen on cognition were measured using the The Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog12). The ADAS-Cog is a structured scale that evaluates memory (word recall, word recognition), reasoning, language (naming, comprehension), orientation, ideational praxis and constructional praxis. The test is scored in terms of errors, with higher scores reflecting poorer performance and greater impairment. Total ADAS-Cog12 scores can range from 0 to 80, with lower scores being better and higher scores being worse. Results of the ADAS-Cog12 for this trial are reported as a raw change score, calculated as the change between the total scores at two evaluation time points (Baseline, Pre-Confinement Visit) with negative scores being better and positive scores being worse.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2016 (estimated)
- Study start2 Mar 2017
- Primary completion10 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Annovis Bio Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Alzheimer's Disease Cooperative Study (ADCS)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02925650
- Sponsor's protocol ID
- QR15001
- Other IDs
- ADC-042-DISC
- Acronym
- DISCOVER
- Status last verified
- May 2023
- First submitted
- 29 Sep 2016
- Last updated
- 9 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data from this research will be shared with other researchers pursuant to the 02/26/2003 "NIH Final Statement on Sharing Research Data". The ADCS through its Data and Sample Sharing Committee (DSSC) will receive requests for sample and data sharing. The ADCS grants access to de-identified data to qualified scientists who complete the request process and agree to conditions in an ADCS/UCSD Data Use Agreement (DUA) and the ADCS Publications Policy. After approval and receipt of the fully executed DUA, applicants are authorized to acquire data. Non-compliance with the DUA, including the requirement to provide requested updates will jeopardize further access to data. The same process and Committee reviews and approves biosample requests. If a request for biosample sharing is approved, a Material Transfer Agreement (MTA) will be negotiated between UCSD/ADCS and the requesting researcher or organization.
Publications
Galasko D, Farlow MR, Lucey BP, Honig LS, Elbert D, Bateman R, Momper J, Thomas RG, Rissman RA, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman HH. 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. Alzheimers Res Ther. 2024 Jul 5;16(1):151. doi: 10.1186/s13195-024-01490-z.
PubMed 38970127Galasko D, Farlow MR, Lucey BP, Honig LS, Elbert D, Bateman R, Momper J, Thomas R, Rissman RA, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman HH. 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. medRxiv [Preprint]. 2024 Mar 22:2024.03.20.24304638. doi: 10.1101/2024.03.20.24304638.
PubMed 38562783
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02925650
- Acronym / sponsor ID
- DISCOVER / QR15001
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's Disease, SILK™, Pharmacodynamics, Safety, Pharmacokinetics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Annovis Bio Inc.Industry (pharma, biotech, devices)
- Collaborators
- Alzheimer's Disease Cooperative Study (ADCS)
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 10 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 6 Oct 2016 (estimated)
- Results
- Posted 9 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the safety and pharmacological effects of 3 different doses of Posiphen® when compared to a placebo, in adult male and female patients with early Alzheimer's disease (AD).
Detailed description
Posiphen®, which was discovered by the US National Institute on Aging (NIA) is a small, orally active, experimental drug that specifically inhibits the synthesis of amyloid precursor protein (APP), Tau and α-Synuclein. It is distinct from other Alzheimer's disease drugs currently in development, because it inhibits the formation of several toxic proteins, rather than removing individual toxic protein after they are produced. Posiphen has potential utility as a disease modifying treatment for AD. The present study will confirm the pharmacokinetics (PK) of Posiphen and its metabolites in plasma and cerebral spinal fluid (CSF). It will also measure the effects of a 23-25 day treatment period with Posiphen on the CSF and plasma levels of a number of biomarkers, inflammatory factors and control proteins. It will also expand the safety data in humans by extending the treatment period from 10 days to a treatment period from 23-25 days. In addition, this study will measure concentrations of various soluble biomarkers in CSF and use the SILK™ assay methods to directly measure the effect of Posiphen on the fractional synthesis rate of Aβ40 in CSF, which will help guide the further development of Posiphen and determine the feasibility of SILK™ in a multicenter trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Experimental | Drug: PosiphenThe study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. |
| Medium Dose | Experimental | Drug: PosiphenThe study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. |
| High Dose | Experimental | Drug: PosiphenThe study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. |
| Placebo | Placebo comparator | Drug: PlaceboThe Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. |
Who may qualify
- Ages
- 55 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female aged 55 to 89 years (inclusive), in good health, no frailty.
- 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.
- Female participants will be given a urine pregnancy test at the screening visit for which they should test negative.
- Clinical profile consistent with MCI or mild AD, consistent with the core clinical criteria outlined in the NIA-AA Guidelines (2011).
- MMSE score between 17 and 30 (inclusive).
Key exclusion criteria (15 listed)
- 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.
- Other neurodegenerative diseases, including Parkinsons disease and Huntingtons disease, or cerebral tumor.
- 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).
- History of a seizure disorder.
- Clinically significant abnormalities in screening laboratory or ECG results.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Posiphenoral solid dosage form capsule | Drug | High Dose, Low Dose, Medium Dose |
| Placebooral solid dosage form capsule | Drug | Placebo |
Primary outcome
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations
Time frame: Up to 25 days
Number of adverse events or study discontinuations, broken down by dose arm (i.e. Low vs. Medium vs. High vs. Placebo), and further broken down by relatedness to Posiphen (Definitely Related, Probably Related, Possibly Related, Unlikely Related, Unrelated)
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.
Mean plasma concentrations of levels of posiphen tartrate, N1 desmethyl posiphen, and N8 desmethyl Posiphen metabolite were determined for each of the three dose cohorts (Low Dose, Medium Dose, High Dose) by a protein precipitation extraction method using a high performance liquid chromatographic mass spectrometric detection method, with a linear weighted regression to determine their concentrations.
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.
Mean CSF concentrations of levels of posiphen tartrate, N1 desmethyl posiphen, and N8 desmethyl Posiphen metabolite were determined for each of the three dose cohorts (Low Dose, Medium Dose, High Dose) by a protein precipitation extraction method using a high performance liquid chromatographic mass spectrometric detection method, with a linear weighted regression to determine the concentrations.
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.
The fractional synthesis rate (FSR) of Aβ40 was measured in the CSF using the SILK™ technique. FSR is a measure of the rate of Aβ synthesis in the brain. During 13C6-leucine infusion, 13C6-leucine is incorporated into newly synthesized proteins throughout the body, including the brain, in proportion to the available 13C6-leucine. This FSR is calculated as the rate of change of the ratio of 13C6-leucine-labeled Aβ proteins to unlabeled Aβ proteins in the lumbar CSF between 6 to 16 hours, normalized to the ratio of labeled to unlabeled leucine amino acid in plasma. It is reported as a fraction of 13C6-leucine-labeled to unlabeled Aβ proteins per hour. The ratio of Aβ in CSF containing 13C6-leucine to that containing unlabeled leucine is measured using mass spectrometry.
7 secondary outcomes
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Rates of Enrollment
Time frame: Up to 25 days
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate %CSF Samples With Enough Volume for Testing
Time frame: Up to 25 days
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction
Time frame: Up to 25 days
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38970127Galasko D, Farlow MR, Lucey BP, Honig LS, Elbert D, Bateman R, Momper J, Thomas RG, Rissman RA, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman HH. 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. Alzheimers Res Ther. 2024 Jul 5;16(1):151. doi: 10.1186/s13195-024-01490-z.
- Derived from this study: PubMed 38562783Galasko D, Farlow MR, Lucey BP, Honig LS, Elbert D, Bateman R, Momper J, Thomas R, Rissman RA, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman HH. 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. medRxiv [Preprint]. 2024 Mar 22:2024.03.20.24304638. doi: 10.1101/2024.03.20.24304638.
- Individual participant dataSharing planned: Yes. Data from this research will be shared with other researchers pursuant to the 02/26/2003 "NIH Final Statement on Sharing Research Data". The ADCS through its Data and Sample Sharing Committee (DSSC) will receive requests for sample and data sharing. The ADCS grants access to de-identified data to qualified scientists who complete the request process and agree to conditions in an ADCS/UCSD Data Use Agreement (DUA) and the ADCS Publications Policy. After approval and receipt of the fully executed DUA, applicants are authorized to acquire data. Non-compliance with the DUA, including the requirement to provide requested updates will jeopardize further access to data. The same process and Committee reviews and approves biosample requests. If a request for biosample sharing is approved, a Material Transfer Agreement (MTA) will be negotiated between UCSD/ADCS and the requesting researcher or organization.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Posiphen in people with Alzheimer's Disease, run by Annovis Bio Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations (time frame: Up to 25 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02925650, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.