What is the mechanism of action of this treatment?

Common treatments for agitation in dementia include dextromethorphan, which acts as an NMDA receptor antagonist and sigma-1 receptor agonist, modulating neurotransmission and reducing excitotoxicity. Quinidine is used to inhibit the metabolism of dextromethorphan, increasing its bioavailability. Antipsychotics like olanzapine and risperidone work by blocking dopamine receptors, reducing psychotic symptoms and agitation. These mechanisms are important as they target different pathways involved in agitation, providing tailored therapeutic options for managing symptoms in dementia patients.

What side effects are associated with this type of intervention?

Common treatments for agitation in dementia, such as dextromethorphan/quinidine (similar to AVP-786), often have side effects including dizziness, nausea, diarrhea, and fatigue. Antipsychotics, another common treatment, can cause sedation, extrapyramidal symptoms, and increased risk of stroke. Serotonergic medications like SSRIs may lead to gastrointestinal disturbances, insomnia, and sexual dysfunction. It is important to start with low doses and monitor for adverse effects to mitigate these risks.

What other types of research exist?

Promising alternatives to AVP-786 for treating agitation in dementia patients include: <ol> <li>Suvorexant: An orexin receptor antagonist that has shown potential in improving sleep quality and reducing delirium risk in dementia patients.</li> <li></li> </ol> Pimavanserin: A selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which has shown efficacy in treating psychosis and agitation in dementia. 3. Brexpiprazole: A serotonin-dopamine activity modulator that has demonstrated effectiveness in reducing agitation in Alzheimer's disease in clinical trials.

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AVP-786 for Agitation in Alzheimer's Disease

Q: What prior FDA approvals exist?

The FDA has approved dextromethorphan/quinidine (Nuedexta) for the treatment of pseudobulbar affect (PBA), which shares some symptomatic overlap with agitation in dementia. Dextromethorphan acts as an NMDA receptor antagonist and sigma-1 receptor agonist, while quinidine inhibits its metabolism, enhancing its efficacy. This combination is being studied for its potential benefits in treating agitation in dementia, similar to the investigational drug AVP-786.

Phase 3

Recruiting

Research Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants with a diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working group criteria

Either out-patients or residents of an assisted-living facility or a skilled nursing home

Must not have

Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline; week 52

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here, typically treatments like AVP-786 may cause changes in mood or behavior, gastrointestinal issues, dizziness, headaches, and potentially increase the risk of falls among elderly patients.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

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

Select...

I live at home, in an assisted living, or a skilled nursing facility.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline; week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline; week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline; week 52 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change from Baseline to Week 52 in the Patient Global Impression of Change (PGIC) Score

Side effects data

From 2019 Phase 3 trial • 387 Patients • NCT02442765

Fall

Diarrhoea

Urinary tract infection

Headache

Somnolence

Agitation

Nausea

Vomiting

Contusion

Dizziness

Sinus bradycardia

Oedema peripheral

Laceration

Electrocardiogram QT prolonged

Osteoarthritis

Dehydration

Delirium

Blood alkaline phosphatase increased

Weight increased

Hot flush

Myalgia

Abdominal pain

Non-cardiac chest pain

Epididymitis

Hypokalaemia

Sepsis

Hip fracture

Rib fracture

Spinal compression fracture

Lipase increased

White blood cell count increased

Cerebrovascular accident

Hydroureter

Nephrotic syndrome

Leukocytosis

Thrombocytopenia

Anaemia

Atrial fibrillation

Ear pain

Meniere's disease

Conjunctival hyperaemia

Conjunctivitis allergic

Rectal haemorrhage

Fatigue

Asthenia

Pain

Upper respiratory tract infection

Cellulitis

Acute sinusitis

Diverticulitis

Gastroenteritis viral

Pharyngitis

Vaginal infection

Skin abrasion

Craniocerebral injury

Hand fracture

Neutrophil count increased

Blood urea increased

Blood glucose increased

Blood lactate dehydrogenase increased

Crystal urine

Electrocardiogram abnormal

Fungal test positive

Gamma-glutamyltransferase increased

Glucose urine present

Haemoglobin decreased

Lymphocyte count increased

Decreased appetite

Hyperglycaemia

Hyperkalaemia

Hyperlipasaemia

Hypomagnesaemia

Malnutrition

Arthralgia

Bursitis

Basal cell carcinoma

Lethargy

Dyskinesia

Metabolic encephalopathy

Tremor

Spontaneous penile erection

Chronic obstructive pulmonary disease

Pneumonia aspiration

Cough

Dyspnoea

Dyspnoea exertional

Epistaxis

Rash

Hypertension

Back pain

Fracture pain

Hypertensive crisis

Bundle branch block left

Haemothorax

Pneumothorax spontaneous

Arthritis infective

Orthostatic hypotension

Alcohol poisoning

Femoral neck fracture

Electrocardiogram ST segment depression

Ischaemic stroke

Syncope

Constipation

Gastrooesophageal reflux disease

Toothache

Dry mouth

Faecal incontinence

Pneumonia

Muscular weakness

Balance disorder

Nephrolithiasis

Pollakiuria

Gait disturbance

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

AVP-786-18

AVP-786-28

Trial Design

3Treatment groups

Experimental Treatment

Group I: AVP-786 (dose 3)Experimental Treatment1 Intervention

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

Group II: AVP-786 (dose 2)Experimental Treatment1 Intervention

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

Group III: AVP-786 (dose 1)Experimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AVP-786

2017

Completed Phase 3

~1340

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for agitation in dementia include dextromethorphan, which acts as an NMDA receptor antagonist and sigma-1 receptor agonist, modulating neurotransmission and reducing excitotoxicity. Quinidine is used to inhibit the metabolism of dextromethorphan, increasing its bioavailability. Antipsychotics like olanzapine and risperidone work by blocking dopamine receptors, reducing psychotic symptoms and agitation. These mechanisms are important as they target different pathways involved in agitation, providing tailored therapeutic options for managing symptoms in dementia patients.

Roles of sigma-1 receptors in Alzheimer's disease.Pseudobulbar affect in multiple sclerosis: toward the development of innovative therapeutic strategies.