AVP-786 for Agitation in Alzheimer's Disease

Recruiting at 154 trial locations

Overseen By Chaz De Naranjo

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Avanir Pharmaceuticals

Disqualifiers: Non-Alzheimer's dementia, Unstable systemic diseases, Myasthenia gravis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

183 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that you should not take any prohibited medications during the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the effectiveness of the drug AVP-786 for treating agitation in Alzheimer's disease?

AVP-786, which is similar to AVP-923 (Nuedexta®), has shown promise in reducing agitation in Alzheimer's patients, as AVP-923 was well tolerated and effective in a phase II trial with over 200 patients. The FDA has also fast-tracked AVP-786, indicating its potential based on existing data. ^{1 2 3 4 5}

Is AVP-786 safe for humans?

AVP-786, which is similar to AVP-923 (Nuedexta®), was well tolerated in a study with over 200 patients with Alzheimer's disease, showing it may be generally safe for humans. ^{1 2 4 5 6}

How is the drug AVP-786 different from other treatments for agitation in Alzheimer's disease?

AVP-786 is unique because it combines deuterated dextromethorphan with quinidine, which helps the drug last longer in the body and reach the brain more effectively. Unlike other treatments, it has been granted fast-track designation by the FDA, indicating its potential as a promising new option for managing agitation in Alzheimer's disease. ^{1 2 6 7 8}

What is the purpose of this trial?

This trial tests a combination of two drugs taken by mouth to help calm severe agitation in people with Alzheimer's disease by balancing brain chemicals.

Eligibility Criteria

This trial is for people with Alzheimer's who've had moderate-to-severe agitation for at least 2 weeks, affecting daily life. They need a reliable caregiver and must have tried non-drug therapies first. It's not for those with other types of dementia or agitation due to another condition, nor for those with serious health issues like uncontrolled diabetes or heart disease.

Inclusion Criteria

Participants with clinically significant, moderate-to-severe agitation for at least 2 weeks prior to Screening that interferes with daily routine per the Investigator's judgment

Participants meeting an additional predetermined blinded eligibility criterion, which will remain blinded to the clinical study site Investigators and staff

, will be randomized to receive either the investigational product or the comparator Participants meeting an additional predetermined blinded eligibility criterion, which will remain blinded to the clinical study site Investigators, will be randomized to receive either the investigational product or the comparator.

Exclusion Criteria

My agitation is not due to Alzheimer's, pain, psychiatric disorders, or delirium.

You have myasthenia gravis.

My dementia is not mainly caused by Alzheimer's disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either AVP-786 or placebo capsules administered twice daily for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AVP-786
• Placebo

Trial Overview The study tests AVP-786 against a placebo to see if it can safely and effectively calm agitation in Alzheimer's patients. Participants will be randomly assigned to receive either the real drug or a placebo without knowing which one they're getting.

Participant Groups

Group I: AVP-786 Experimental Treatment 1 Intervention

Participants will be assigned to treatment with AVP-786 capsules administered twice a day over a 12-week period.

Group II: Placebo Placebo Group 1 Intervention

Participants will be assigned to treatment with placebo capsules administered twice a day over a 12-week period.

Who Is Running the Clinical Trial?

Avanir Pharmaceuticals

Lead Sponsor

Trials

32

Recruited

12,100+

Otsuka Pharmaceutical Development & Commercialization, Inc.

Lead Sponsor

Trials

271

Recruited

170,000+

John Kraus

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Medical Officer since 2023

MD, PhD

Tarek Rabah

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Executive Officer since 2022

BS in Biology and BA in Business from the American University of Beirut, MBA from McGill University

Findings from Research

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 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]

In a case series involving 20 patients with agitation due to Alzheimer's disease, 65% responded positively to low-dose divalproex treatment, indicating its potential efficacy in managing behavioral disturbances.

The study also found that 25% of patients experienced adverse events, suggesting that while low-dose divalproex can improve behavior, there is still a risk of side effects that needs to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose divalproex in agitated patients with Alzheimer's disease. Dolder, C., McKinsey, J.[2013]

In a 10-week study involving 208 patients with Alzheimer's Disease-associated psychosis, aripiprazole demonstrated significantly greater improvements in psychotic symptoms compared to placebo, particularly on the Brief Psychiatric Rating Scale (BPRS).

Aripiprazole was found to be safe and well-tolerated, with mild to moderate adverse effects, and no significant differences in extrapyramidal symptoms or other serious side effects compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: a randomized, placebo-controlled study. De Deyn, P., Jeste, DV., Swanink, R., et al.[2022]

In a study involving 487 patients with Alzheimer's dementia and psychosis, aripiprazole at 10 mg/day significantly improved psychotic symptoms and agitation compared to placebo, demonstrating its efficacy in this population.

While aripiprazole was generally safe, there were reports of cerebrovascular adverse events, particularly at higher doses, highlighting the need for careful monitoring when prescribing atypical antipsychotics to elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. Mintzer, JE., Tune, LE., Breder, CD., et al.[2022]

References

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

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

2. 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]

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

Low-dose divalproex in agitated patients with Alzheimer's disease. [2013]

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

Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: a randomized, placebo-controlled study. [2022]

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

A randomized, double-blind, placebo-controlled tolerability study of intramuscular aripiprazole in acutely agitated patients with Alzheimer's, vascular, or mixed dementia. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. [2022]

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

Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. [2023]

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

New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer's disease: focus on brexpiprazole and pimavanserin. [2020]