AVP-786 for Agitation in Alzheimer's Disease

Recruiting at 291 trial locations

Overseen By Uma Atmuri

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Must not be taking: Nuedexta

Disqualifiers: Malignancy, Unstable cardiac, others

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

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: 52 weeks

1197 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a medication called AVP-786 on individuals who have taken part in previous studies. The goal is to see if this medication can help with their conditions over time.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used NUEDEXTA® in the 2 weeks before starting the trial.

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 is generally safe for humans. ^{1 2 3 4 5}

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 stay in the body longer and penetrate 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 3 6 7}

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

AVP-786 is similar to AVP-923, which reduced agitation in Alzheimer's patients and was well tolerated in a study with over 200 participants. The FDA has also fast-tracked AVP-786, indicating its potential based on existing data. ^{1 2 4 5 8}

Are You a Good Fit for This Trial?

This trial is for patients with Alzheimer's-related dementia who've completed certain earlier studies (15-AVP-786-301, 302, 12-AVR-131, or 17-AVP-786-305). They should be experiencing moderate to severe agitation and have a specific level of cognitive function. It's open to out-patients or those in assisted living/nursing homes but not for individuals at high risk of falls or with other serious health issues that could affect safety results.

Inclusion Criteria

Participant has successfully completed Studies 15-AVP-786-301, 15-AVP-786-302, 12-AVR-131, or 17-AVP-786-305. (Note: A delay in enrollment may include delays associated with COVID-19 restrictions.)

If you sign up late, you must have a specific score on a test that checks your memory and thinking abilities.

I have been diagnosed with Alzheimer's Disease based on NIA-AA criteria.

Exclusion Criteria

I do not have any major health issues that could affect the study's safety results.

The doctor thinks you might be at a high risk of falling during the study.

I am currently using or have used NUEDEXTA® within the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AVP-786 capsules twice a day over a 52-week period

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label extension

Participants continue to receive AVP-786 in a long-term extension study

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AVP-786

Trial Overview The study tests the long-term safety and effectiveness of AVP-786 as a treatment for agitation in Alzheimer's disease patients. This extension includes participants from previous Phase 2 and Phase 3 trials on the same medication.

How Is the Trial Designed?

Group I: AVP-786 (dose 3) Experimental Treatment 1 Intervention

AVP-786 dose 3; capsules administered twice a day over a 52-week period

Group II: AVP-786 (dose 2) Experimental Treatment 1 Intervention

AVP-786 dose 2; capsules administered twice a day over a 52-week period

Group III: AVP-786 (dose 1) Experimental Treatment 1 Intervention

AVP-786 dose 1; capsules administered twice a day over a 52-week period

Who Is Running the Clinical Trial?

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

Avanir Pharmaceuticals

Lead Sponsor

Trials

32

Recruited

12,100+

Published Research Related to This Trial

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]

Citations

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]