AVP-786 for Alzheimer's-related Agitation

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

241 Participants Needed

Trial Summary

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.

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.

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

AVP-786, which includes dextromethorphan and quinidine, has shown promise in reducing agitation in Alzheimer's patients, as seen in a phase II trial of a similar drug, AVP-923, which was well tolerated and effective. The FDA has also fast-tracked AVP-786, indicating its potential based on existing data. ^{1 2 3 4 5}

How is the drug AVP-786 unique for treating Alzheimer's-related agitation?

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. This combination has shown promise in reducing agitation in Alzheimer's patients and has been granted fast-track designation by the FDA, indicating its potential as a novel treatment option. ^{1 2 3 6 7}

Eligibility Criteria

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

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 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.

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 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 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]

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. 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]

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

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

7. 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]