NMRA-323511 for Agitation in Alzheimer's Disease

Recruiting at 19 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Neumora Therapeutics, Inc.

Must not be taking: Anticonvulsants

Disqualifiers: Epilepsy, Suicidal, Neurologic disorder, others

Compensation: Varies

Number of Visits: 2

96 Participants Needed

Trial Summary

What is the purpose of this trial?

This study consists of 2 parts, Part A and Part B. Part A is a single center, randomized, double-blind, placebo-controlled cohort designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of NMRA-323511 among healthy elderly. Part B is a multicenter, randomized, double-blinded, placebo-controlled, parallel-group cohort to evaluate the safety, tolerability, and efficacy of NMRA-323511 among adults with Agitation Associated with Dementia due to Alzheimer's Disease. Part A consists of a Screening Period (up to 28 days), a 10-day Treatment Period, and a 10- day Follow-up clinic visit after last dose of study treatment. Part B consists of a Screening Period (up to 28 days), an 8-week Treatment Period, and a 10-day Follow-up clinic visit after last dose of study treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug NMRA-323511 for agitation in Alzheimer's disease?

Research on similar drugs like memantine shows that it can help reduce agitation in Alzheimer's patients, suggesting that NMRA-323511 might have similar benefits. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for healthy elderly individuals and adults with agitation due to Alzheimer's dementia. Participants must pass a screening and be eligible based on specific criteria not detailed here.

Inclusion Criteria

I am between 65 and 80 years old with a BMI between 18 and 32.

I am 55-90 years old, diagnosed with Alzheimer's, have agitation, and my MMSE score is 5-24.

Do you experience agitation or irritation related to not being able to remember things?

Exclusion Criteria

I have dementia or memory issues not caused by Alzheimer's, or another significant neurological condition.

Have you been diagnosed with a serious health condition outside of Alzheimer's?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment (Part A)

Participants receive NMRA-323511 or placebo for 10 days to evaluate safety, tolerability, and pharmacokinetics

10 days

Follow-up (Part A)

Participants are monitored for safety and effectiveness after treatment

10 days

1 clinic visit

Treatment (Part B)

Participants receive NMRA-323511 or placebo for 8 weeks to evaluate safety, tolerability, and efficacy

8 weeks

Follow-up (Part B)

Participants are monitored for safety and effectiveness after treatment

10 days

1 clinic visit

Treatment Details

Interventions

• NMRA-323511

Trial Overview The study tests NMRA-323511 against a placebo in two parts: Part A focuses on safety in healthy elderly, while Part B assesses safety and effectiveness in those with Alzheimer's-related agitation.

Participant Groups

Group I: Part B: NMRA-323511 Experimental Treatment 1 Intervention

Group II: Part A: NMRA-323511 Experimental Treatment 1 Intervention

Group III: Part A: Placebo Placebo Group 1 Intervention

Group IV: Part B: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Neumora Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

2,100+

Findings from Research

Switching from donepezil to galantamine in patients with Alzheimer's disease showed improvements in agitation after 8 weeks, indicating that this switch is a safe and effective treatment option.

Adding memantine to existing donepezil therapy was also found to be effective in reducing agitation compared to simply increasing the donepezil dose, suggesting that both strategies can provide meaningful benefits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically meaningful treatment responses after switching to galantamine and with addition of memantine in patients with Alzheimer's disease receiving donepezil. Kano, O., Ito, H., Takazawa, T., et al.[2021]

In a study involving 10 patients with probable Alzheimer's disease, buspirone was found to significantly reduce agitation scores, indicating its potential efficacy for managing agitation in this population.

The optimal average dose for achieving a significant decrease in agitation was 35 mg/day, suggesting that lower doses may be effective before reaching the maximum dose of 60 mg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Buspirone on Agitation Associated With Dementia. Sakauye, KM., Camp, CJ., Ford, PA.[2019]

In a study involving 149 participants with moderate-to-severe Alzheimer's disease, memantine did not show a significant improvement in clinically significant agitation compared to placebo after 6 weeks, indicating it may not be effective for this symptom.

However, memantine did demonstrate a positive effect on cognitive function and showed some benefits in reducing neuropsychiatric symptoms, suggesting it may still have a role in managing other aspects of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial. Fox, C., Crugel, M., Maidment, I., et al.[2022]

In two 12-week studies involving a total of 703 patients with agitation in Alzheimer's dementia, brexpiprazole at a dose of 2 mg/day showed significant improvement in agitation symptoms compared to placebo, indicating its efficacy in this patient population.

Brexpiprazole was generally well tolerated, with most treatment-emergent adverse events being mild to moderate, although headaches and insomnia were reported more frequently than with placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials. Grossberg, GT., Kohegyi, E., Mergel, V., et al.[2021]

Memantine 20 mg once daily has been shown to improve cognition, functional ability, and behavioral symptoms in patients with moderate to severe Alzheimer's disease, based on pooled clinical trials and real-world studies.

The use of memantine is associated with delays in the need for full-time care, potentially leading to cost savings compared to standard care, and it has a safety profile similar to that of a placebo, indicating it is well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily memantine: a guide to its use in moderate to severe Alzheimer's disease in the EU. Lyseng-Williamson, KA., McKeage, K.[2021]

References

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

Clinically meaningful treatment responses after switching to galantamine and with addition of memantine in patients with Alzheimer's disease receiving donepezil. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Effects of Buspirone on Agitation Associated With Dementia. [2019]

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

Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials. [2021]

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

Once-daily memantine: a guide to its use in moderate to severe Alzheimer's disease in the EU. [2021]