AVP-786 for Alzheimer's-related Agitation

Not currently recruiting at 165 trial locations

Overseen By Otsuka Call Center

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 for individuals with Alzheimer's disease who experience significant agitation. The goal is to evaluate the treatment's effectiveness and safety compared to a placebo (a pill with no active ingredients). Suitable candidates have Alzheimer's, experience agitation that disrupts their daily routine, and require medication to manage these symptoms. Participants also need a reliable caregiver to assist with study requirements. 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 caregivers should not give any prohibited medications during the study. It's best to discuss your current medications with the study team to see if any are prohibited.

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

Research shows that AVP-786 is being tested for its safety in treating agitation in people with Alzheimer's. Earlier studies found that AVP-786 was generally well-tolerated, though some patients experienced more falls, with about 8.6% to 9.1% of participants in different dose groups reporting this issue. AVP-786 consists of two ingredients: deudextromethorphan hydrobromide and quinidine sulfate. These ingredients have been used in other treatments, providing some information about their safety. Overall, while AVP-786 appears promising, side effects, particularly the risk of falls, should be considered. ^{1 2 3 4 5}

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

Unlike the standard treatments for Alzheimer's-related agitation, such as antipsychotics and antidepressants, AVP-786 is designed to work differently by targeting the brain's neurotransmitter systems. It combines deuterated dextromethorphan with quinidine, which may enhance its effectiveness in reducing agitation symptoms. Researchers are excited about AVP-786 because it might offer a more targeted approach with potentially fewer side effects, providing a promising new option for managing agitation in Alzheimer's patients.

What evidence suggests that AVP-786 could be an effective treatment for Alzheimer's-related agitation?

Research shows that AVP-786, a mix of two ingredients, may help reduce restlessness in people with Alzheimer's disease. Participants in this trial will receive either AVP-786 or a placebo. Earlier studies found that a similar drug, AVP-923, helped lower restlessness in Alzheimer's patients and was well tolerated. However, some recent tests of AVP-786 did not achieve their main goals, with results not as strong as hoped. Despite this, ongoing research aims to better understand its potential benefits. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people with Alzheimer's who show moderate-to-severe agitation. They must have been diagnosed according to specific criteria, need medication as judged by a doctor, and have had non-drug treatments tried first. A reliable caregiver must be involved. Those with non-Alzheimer's dementia or conditions like myasthenia gravis can't join.

Inclusion Criteria

You have been diagnosed with Alzheimer's Disease

I have a caregiver who can help me with my treatment and follows the study rules.

I have been diagnosed with Alzheimer's disease based on specific criteria.

Exclusion Criteria

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

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

You have myasthenia gravis.

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 helps calm agitation in Alzheimer's patients better than no treatment at all. Participants will not know whether they're getting the real medicine or the placebo.

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 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]

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]

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]

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. 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- ...

3. 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.

4. 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 ...

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/20-AVP-786-307

Study to Assess the Efficacy, Safety, and Tolerability of AVP ... This study was conducted to evaluate the efficacy, safety, and tolerability of AVP-786 (deudextromethorphan hydrobromide \[d6-DM\]/quinidine sulfate \[Q\]) ...

7. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/a-study-of-avp-786-for-agitation-in-patients-with-alzheimers-dementia-3/

A study of AVP-786 for agitation in patients ... This study is looking at a drug called AVP-786, it is anticipated that AVP-786 will have a positive effect on agitation in patients with Alzheimer's dementia.