AVP-786 for Agitation in Alzheimer's Disease

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AVP-786 to determine its effectiveness in reducing agitation in people with Alzheimer's disease. Researchers aim to assess whether AVP-786 is safe and effective compared to a placebo (a pill with no active medicine). Participants will take capsules twice a day for 12 weeks. The trial seeks individuals diagnosed with Alzheimer's who have experienced moderate to severe agitation disrupting their daily lives for at least two weeks. Participants need a caregiver to assist with study tasks and medication routines. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that AVP-786 is likely to be safe for humans?

Research has shown that AVP-786 has been tested in people with Alzheimer's disease to treat agitation. Some patients tolerate it well, but side effects have occurred. For instance, one study found that people taking AVP-786 experienced more falls than those on a placebo. Specifically, 8.6% of patients in the high-dose group and 9.1% in the low-dose group experienced falls.

Despite these side effects, earlier trials generally suggest that many patients tolerate AVP-786 well. This treatment is still under study to better understand its safety and effectiveness. While there are positive signs, some risks remain. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

AVP-786 is unique because it combines dextromethorphan and quinidine, aiming to reduce agitation in Alzheimer's patients. Unlike standard treatments that often focus on neurotransmitters like acetylcholine or glutamate, AVP-786 works differently by modulating the sigma-1 and NMDA receptors. Researchers are excited about this treatment because it offers a novel approach that could improve symptoms with potentially fewer side effects compared to current options.

What evidence suggests that AVP-786 might be an effective treatment for agitation in Alzheimer's disease?

In this trial, participants will receive either AVP-786 or a placebo. Research has shown that AVP-786 has been studied for treating restlessness in people with Alzheimer's. One study found that AVP-786 helped reduce restlessness and was safe for over 200 patients. However, another study found it did not outperform a placebo. While there is some hope, further research is needed to confirm its effectiveness for restlessness in Alzheimer's disease. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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

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

, 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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.

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 announce topline results of the phase 3 clinical trial of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer's disease.

2.

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.

3.

pubmed.ncbi.nlm.nih.gov

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

AVP-786 for the treatment of agitation in dementia ...

AVP-923 reduced agitation in AD and was well tolerated in a phase II RCT that included more than 200 patients. A phase III clinical development program of AVP- ...

4.

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 ...

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 ...

The experimental drug failed to meet the primary efficacy endpoint of the study, which is the change from baseline to week 12 in the Cohen- ...

6.

trials.otsuka-us.com

trials.otsuka-us.com/trials/15-AVP-786-303

Long Term, Extension Study of the Safety and Efficacy ...

Long term, extension study of the safety and efficacy of AVP-786 for the treatment of agitation in patients with dementia of the Alzheimer's type.