AMDX-2011P for Alzheimer's Disease

Recruiting at 2 trial locations

Overseen By David Bingaman, DVM, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amydis Inc.

Disqualifiers: Glaucoma, Macular degeneration, Cardiac arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 day

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess safety, tolerability, plasma pharmacokinetics and biologic activity of a single intravenous dose of AMDX-2011P in participants with Alzheimer's Disease (AD).

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial investigators for more details.

What data supports the idea that AMDX-2011P for Alzheimer's Disease is an effective treatment?

The available research does not provide any specific data on the effectiveness of AMDX-2011P for Alzheimer's Disease. Instead, it discusses other treatments like donepezil and acetyl-L-carnitine. Donepezil has been shown to be effective in both mild to moderate and more severe stages of Alzheimer's Disease, while acetyl-L-carnitine showed potential benefits for younger patients with early-onset Alzheimer's. However, there is no information on AMDX-2011P in the provided research. ^{1 2 3 4 5}

What safety data is available for AMDX-2011P in Alzheimer's treatment?

The provided research does not mention AMDX-2011P or its variants directly. Therefore, no specific safety data for AMDX-2011P is available in the given studies. The studies focus on other treatments like LY451395, AL-108, idalopirdine, and AVP-786, each with their own safety profiles, but none of these are identified as AMDX-2011P. ^{4 6 7 8 9}

Is the drug AMDX-2011P a promising treatment for Alzheimer's Disease?

The information provided does not mention AMDX-2011P, so we cannot determine if it is a promising treatment for Alzheimer's Disease based on the given research articles. ^{3 4 10 11 12}

Research Team

David Bingaman, DVM, PhD

Principal Investigator

Amydis Inc.

Eligibility Criteria

This trial is for individuals with Alzheimer's Disease confirmed by a PET brain scan. Participants must be willing to undergo genetic testing and retinal imaging, and have the ability to fixate during these procedures. Those with heart rhythm issues, significant ECG abnormalities, psychological conditions likely to prevent study completion, glaucoma or certain forms of macular degeneration cannot join.

Inclusion Criteria

I am willing to undergo genetic testing for APOE.

Ability to fixate and undergo retinal imaging of both eyes

I have Alzheimer's with a positive amyloid PET scan.

Exclusion Criteria

My heart's electrical activity is normal as per my last ECG.

Presence of any underlying physical or psychological medical condition that, in the opinion of the investigator, would make it unlikely that the participant will complete the study per protocol

I have been diagnosed with or suspected of having glaucoma by an eye doctor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive a single intravenous bolus injection of AMDX-2011P followed by safety assessments, retinal imaging, and PK blood collection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including detection of amyloid deposits in the retina

8 days

1 visit (in-person)

Treatment Details

Interventions

• AMDX-2011P

Trial Overview The study tests AMDX-2011P administered as a single intravenous dose in people with Alzheimer's Disease. It aims to evaluate the safety, how well it's tolerated, its presence in blood over time (pharmacokinetics), and its biological effects on patients.

Participant Groups

Group I: AMDX-2011P 100 milligram Experimental Treatment 1 Intervention

AMDX2011P 100 milligram (4 milliliter) single bolus injection intravenous for diagnostic review

Who Is Running the Clinical Trial?

Amydis Inc.

Lead Sponsor

Trials

4

Recruited

140+

Findings from Research

In a 132-week study involving 579 patients with mild to moderate Alzheimer's disease, donepezil demonstrated long-term efficacy, with cognitive improvements observed after 6 weeks of treatment and slight improvements in dementia ratings over the first 12 weeks.

Donepezil was generally well tolerated, although 85% of patients experienced at least one adverse event, with common side effects including diarrhea, nausea, and infections, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of donepezil over 3 years: an open-label, multicentre study in patients with Alzheimer's disease. Burns, A., Gauthier, S., Perdomo, C.[2018]

The fixed-dose combination (FDC) capsule of 28 mg memantine extended release and 10 mg donepezil is bioequivalent to the separately administered medications, which may enhance treatment adherence for Alzheimer's disease.

The bioavailability of the FDC is not affected by food intake or by sprinkling the capsule contents on applesauce, indicating flexible administration options without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel once-daily fixed-dose combination of memantine extended release and donepezil for the treatment of moderate to severe Alzheimer's disease: two phase I studies in healthy volunteers. Boinpally, R., Chen, L., Zukin, SR., et al.[2022]

In a 1-year study involving 431 patients with probable Alzheimer's disease, acetyl-L-carnitine hydrochloride (ALCAR) did not show a significant difference in cognitive decline compared to placebo for the overall group, indicating similar efficacy between the two treatments.

However, a subanalysis suggested that early-onset Alzheimer's patients (aged 65 or younger) may experience a slower decline with ALCAR compared to those on placebo, while late-onset patients may progress more rapidly on ALCAR, highlighting the need for further research in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Thal, LJ., Carta, A., Clarke, WR., et al.[2019]

In a study involving 144 subjects with amnestic mild cognitive impairment, AL-108 was found to be generally safe and well tolerated over 12 weeks of treatment.

While the overall efficacy analysis did not show a significant difference in cognitive memory scores between AL-108 and placebo, there were promising signals of potential efficacy in specific memory and attention tasks, suggesting further research is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Morimoto, BH., Schmechel, D., Hirman, J., et al.[2016]

In a study of 290 patients with moderate to severe Alzheimer's disease, donepezil significantly improved global, cognitive, functional, and behavioral measures compared to placebo over 24 weeks, particularly in patients with more severe symptoms (sMMSE score 5-12).

The treatment effects of donepezil were consistent across varying levels of disease severity, indicating its efficacy is not limited to a specific stage within moderate to severe Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial. Feldman, H., Gauthier, S., Hecker, J., et al.[2018]

In an 11-week study involving 181 patients with mild to moderate Alzheimer's disease, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 did not show significant improvement in cognitive function compared to placebo, as measured by the ADAS-Cog scale.

While there were some marginal improvements in neuropsychiatric symptoms after 8 weeks of treatment, the overall safety profile was similar between LY451395 and placebo, with most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Chappell, AS., Gonzales, C., Williams, J., et al.[2022]

Idalopirdine, when used as an adjunctive therapy in patients with mild to moderate Alzheimer's disease, demonstrated good tolerability over an extended period of up to 18 months, with treatment-emergent adverse events reported in 51-59% of patients, but no new safety concerns were identified.

Despite its safety profile, idalopirdine did not show consistent efficacy benefits when added to donepezil or memantine, indicating that while it is safe for long-term use, it may not provide significant therapeutic advantages in treating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Multicenter, Phase III Extension Study of Idalopirdine as Adjunctive to Donepezil for the Treatment of Mild-Moderate Alzheimer's Disease. Frölich, L., Atri, A., Ballard, C., et al.[2020]

AVP-786, a new investigational drug combining deuterated dextromethorphan and quinidine, shows promise for treating agitation in Alzheimer-type dementia, with a favorable pharmacokinetic profile that enhances its effectiveness and safety.

Previous studies, including a phase II trial with over 200 patients, indicated that AVP-923 (a related compound) effectively reduced agitation and was well tolerated, supporting the potential of AVP-786 in ongoing phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AVP-786 for the treatment of agitation in dementia of the Alzheimer's type. Garay, RP., Grossberg, GT.[2017]

In a study of 250 Alzheimer's patients in Brazil, 83.6% reported at least one adverse drug reaction (ADR), with rivastigmine causing the highest number of ADRs at an average of 7.9 per patient.

Most ADRs were mild and related to psychiatric disorders, highlighting the need for improved safety measures in prescribing Alzheimer's medications, especially given the patients' vulnerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency and Severity of Adverse Drug Reactions to Medications Prescribed for Alzheimer's Disease in a Brazilian City: Cross-Sectional Study. Ferreira, TR., Lopes, LC., Bergamaschi, CC.[2021]

Current Alzheimer's disease treatments mainly focus on improving symptoms rather than halting disease progression, with only selegiline and vitamin E showing any delay in important clinical endpoints.

Research is ongoing for new treatments aimed at slowing progression or preventing onset, including antioxidants, anti-inflammatory agents, and drugs targeting amyloid deposition, with trials also focusing on preventing Alzheimer's in individuals with mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials to slow progression and prevent disease onset. Thal, LJ.[2019]

Carbon-11 labeled acetylcholine analogues, [11C]MP4A and [11C]MP4P, effectively measure brain acetylcholinesterase (AChE) activity in vivo, revealing significant reductions in AChE activity associated with various types of dementia, particularly in early-onset Alzheimer's disease.

The study found that AChE activity is notably reduced in the cerebral cortex of patients with Alzheimer's disease, Parkinson's disease with dementia, and dementia with Lewy bodies, indicating that these measurements could help in understanding the progression of neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Imaging of brain acetylcholinesterase activity in dementias and extrapyramidal disorders]. Shinotoh, H.[2008]

In a study of 201 sedentary older adults with amnestic mild cognitive impairment (aMCI), slower usual gait speed and longer times on the Timed 'Up & Go' Test were significantly associated with poorer performance on executive function tests, indicating a link between physical performance and cognitive abilities.

These findings suggest that monitoring gait and mobility could be important for assessing cognitive decline in older adults with aMCI, although the study's cross-sectional design means we cannot determine if one directly causes the other.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between physical performance and executive function in older adults with mild cognitive impairment: gait speed and the timed "up & go" test. McGough, EL., Kelly, VE., Logsdon, RG., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of donepezil over 3 years: an open-label, multicentre study in patients with Alzheimer's disease. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

A novel once-daily fixed-dose combination of memantine extended release and donepezil for the treatment of moderate to severe Alzheimer's disease: two phase I studies in healthy volunteers. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Open-Label, Multicenter, Phase III Extension Study of Idalopirdine as Adjunctive to Donepezil for the Treatment of Mild-Moderate Alzheimer's Disease. [2020]

8. England pubmed.ncbi.nlm.nih.gov

AVP-786 for the treatment of agitation in dementia of the Alzheimer's type. [2017]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Frequency and Severity of Adverse Drug Reactions to Medications Prescribed for Alzheimer's Disease in a Brazilian City: Cross-Sectional Study. [2021]

10. Austria pubmed.ncbi.nlm.nih.gov

Trials to slow progression and prevent disease onset. [2019]

11. Japan pubmed.ncbi.nlm.nih.gov

[Imaging of brain acetylcholinesterase activity in dementias and extrapyramidal disorders]. [2008]

12. United States pubmed.ncbi.nlm.nih.gov

Associations between physical performance and executive function in older adults with mild cognitive impairment: gait speed and the timed "up & go" test. [2022]