AVP-786 for Agitation in Alzheimer's Disease

No longer recruiting at 304 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called AVP-786, an experimental drug, to help manage agitation in people with Alzheimer's disease. Agitation can unsettle those with Alzheimer's, causing restlessness or distress. The study tests different doses of AVP-786 to evaluate their effectiveness over time. Individuals who completed previous related studies and experience noticeable agitation due to Alzheimer's might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AVP-786 has been tested for safety in people with Alzheimer's who experience agitation. Studies have found that AVP-786 is generally well tolerated, though some side effects have been reported. Specifically, one study found that falls were more common among those taking AVP-786, with 8.6% in the high-dose group and 9.1% in the low-dose group experiencing falls. While many people do not encounter serious problems with the treatment, risks related to balance should be considered. It is important to consult a healthcare provider about potential side effects before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AVP-786 for treating agitation in Alzheimer's disease because it leverages a unique combination of dextromethorphan (DM) and quinidine (Q), which may offer a novel mechanism of action compared to current treatments. While existing options like antipsychotics and benzodiazepines focus on sedative effects or altering neurotransmitter levels, AVP-786 targets NMDA receptors in the brain, potentially reducing agitation with fewer side effects. This innovative approach could provide a more targeted and safer treatment for patients, offering hope for improved management of this challenging symptom.

What evidence suggests that this trial's treatments could be effective for agitation in Alzheimer's disease?

Research has shown that AVP-786 has been tested for reducing agitation in people with Alzheimer's. However, previous studies have not clearly proven its effectiveness for this purpose. Some experts believe that changes to the drug's formula might have reduced its effectiveness. Despite these concerns, AVP-786 remains under study in this trial, with participants receiving dosages of 18 mg, 28 mg, or 42.63 mg. Reviewing all research and consulting healthcare providers is important before deciding to join a clinical trial. ^{1 2 5 6 7}

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.

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

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

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 42.63 mg Experimental Treatment 1 Intervention

Participants who received placebo in the previous studies 15-AVP-786-301 (NCT02442765), 15-AVP-786-302 (NCT02442778), or 17-AVP-786-305 (NCT03393520) and those who had delayed enrolment, started AVP-786-28/4.9 (d6-DM 28 mg/Q 4.9 mg) in the current study and were eventually titrated to receive AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg) capsules, twice a day for 52 weeks.

Group II: AVP-786 28 mg Experimental Treatment 1 Intervention

Participants who received AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) capsules in the previous studies 15-AVP-786-301 (NCT02442765), 15-AVP-786-302 (NCT02442778), or 17-AVP-786-305 (NCT03393520) continued to receive AVP-786-28 (d6-DM 28 mg/Q 4.9 mg), capsules, twice a day for 52 weeks in the current study.

Group III: AVP-786 18 milligrams (mg) Experimental Treatment 1 Intervention

Participants who received AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) capsules in the previous studies 15-AVP-786-301 (NCT02442765), 15-AVP-786-302 (NCT02442778), or 17-AVP-786-305 (NCT03393520) continued to receive AVP-786-18 (d6-DM 18 mg/Q 4.9 mg), capsules, twice a day for 52 weeks in the current study.

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 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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02442765

NCT02442765 | Efficacy, Safety and Tolerability of AVP- ... Efficacy, Safety and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type. ClinicalTrials.gov ID NCT02442765.

2. otsuka-us.com otsuka-us.com/news/otsuka-announces-phase-3-topline-results-avp-786-treatment-agitation-associated-dementia-due

Otsuka Announces Phase 3 Topline Results of AVP-786 in ... Otsuka Announces Phase 3 Topline Results of AVP-786 in the Treatment of Agitation Associated With Dementia Due to Alzheimer's Disease.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27936965/

AVP-786 for the treatment of agitation in dementia ... Expert opinion: AVP-786 is one of six investigational compounds in recent phase III clinical development for agitation in Alzheimer disease (AD).

4. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-025-01780-0

Deuteration may reduce the efficacy of dextromethorphan in ... We hypothesize that AVP-786 failed to demonstrate efficacy in treating agitation in AD dementia due to the negative impact of deuteration on dextromethorphan's ...

5. alzheimer-europe.org alzheimer-europe.org/news/otsuka-reports-phase-iii-topline-results-avp-786-ad-agitation?language_content_entity=en

Otsuka reports Phase III topline results of AVP-786 for AD ... During the trial, the incidence of falls was higher in participants receiving AVP-786, with 8.6% in the high dose group and 9.1% in the low dose ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03393520

Study Details | NCT03393520 | Assessment of the Efficacy, ... This study will be conducted to evaluate the efficacy, safety, and tolerability of AVP-786 compared to placebo, for the treatment of agitation in participants ...

7. neurologylive.com neurologylive.com/view/avp-786-falls-short-phase-3-study-alzheimer-disease-agitation

AVP-786 Falls Short in Phase 3 Study of Alzheimer ... All told, patients treated with AVP-786 did not experience a statistically significant improvement in agitation compared with placebo, as ...