What side effects are associated with this type of intervention?

Common treatments for agitation in dementia, such as AVP-786 (deudextromethorphan hydrobromide/quinidine sulfate), antipsychotics, and serotonergic medications, have various side effects. AVP-786 may cause dizziness, diarrhea, and urinary tract infections. Antipsychotics, including both typical and atypical, can lead to sedation, parkinsonism, dystonia, akathisia, and hypotension. Serotonergic medications, like SSRIs, may result in gastrointestinal disturbances, insomnia, and sexual dysfunction. It is crucial to monitor for these side effects and adjust treatment as necessary.

What prior FDA approvals exist?

Currently, there are no FDA-approved treatments specifically for agitation in dementia that combine an NMDA receptor antagonist and a CYP2D6 inhibitor like AVP-786. However, dextromethorphan/quinidine (Nuedexta) is approved for pseudobulbar affect and has been studied off-label for agitation in dementia. Other treatments for agitation in dementia include antipsychotics such as risperidone and olanzapine, though these are not without significant side effects. The ongoing study of AVP-786 aims to address this gap by evaluating its efficacy and safety for this specific condition.

What other types of research exist?

Promising novel alternatives to AVP-786 for treating agitation in dementia patients include Brexpiprazole, a serotonin-dopamine activity modulator, and Pimavanserin, a selective serotonin inverse agonist and antagonist. Both have shown efficacy in clinical trials for managing neuropsychiatric symptoms in dementia patients.

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AVP-786 for Agitation in Alzheimer's Disease

Verified Trial

Phase 3

Recruiting

Research Sponsored by Avanir Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

Diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation.

Participants with a diagnosis of probable Alzheimer's disease according to the 2011 Neuropsychiatric Inventory Agitation/Aggression (NPI-AA) working groups criteria

Must not have

Participants with dementia predominantly of the non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)

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 [except skin basal-cell carcinoma], 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 12

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here, common concerns may include potential reactions related to the nervous system (like dizziness), gastrointestinal issues (such as nausea), and possible interactions with other medications.

Eligibility Criteria

Inclusion Criteria

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

Select...

My agitation is officially diagnosed according to the IPA standards.

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I have been diagnosed with Alzheimer's disease.

Exclusion Criteria

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

Select...

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

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 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline; week 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline; week 12 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change from Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score

Secondary study objectives

Change from Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGI-S) Score, as Related to Agitation

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

Myalgia

Weight increased

Hot flush

Blood alkaline phosphatase increased

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

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: AVP-786Experimental Treatment1 Intervention

Participants will be assigned to treatment with AVP-786 capsules administered twice a day over a 12-week period.

Group II: PlaceboPlacebo Group1 Intervention

Participants will be assigned to treatment with placebo capsules administered twice a day over a 12-week period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AVP-786

2017

Completed Phase 3

~1340

0 / 4Eligibility 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, such as AVP-786, work through mechanisms like NMDA receptor antagonism and sigma-1 receptor agonism. Deudextromethorphan hydrobromide in AVP-786 modulates glutamate activity and provides neuroprotective effects, while quinidine sulfate increases its bioavailability by inhibiting CYP2D6. These actions are crucial as they help reduce excitotoxicity, neuroinflammation, and agitation, improving the quality of life for dementia patients.

Can pharmacological treatment of behavioural disturbances in elderly patients with dementia lower the burden of their family caregiver?