What side effects are associated with this type of intervention?

Common treatments for agitation in dementia, such as deudextromethorphan hydrobromide (an NMDA receptor antagonist and sigma-1 receptor agonist) combined with quinidine sulfate (a CYP2D6 inhibitor), can have side effects including dizziness, nausea, and potential cardiac issues due to quinidine's effect on heart rhythm. Antipsychotics like olanzapine and risperidone may cause sedation, weight gain, and an increased risk of stroke. Cholinesterase inhibitors, such as rivastigmine, can lead to gastrointestinal issues like nausea and diarrhea. It is important to monitor these side effects and adjust treatment as necessary under medical supervision.

What prior FDA approvals exist?

There have been no specific FDA approvals for the treatment of agitation in dementia using a combination similar to AVP-786 (deudextromethorphan hydrobromide and quinidine sulfate). However, dextromethorphan combined with quinidine (Nuedexta) has been approved for pseudobulbar affect, a condition with some overlapping symptoms. This combination leverages dextromethorphan's NMDA receptor antagonism and sigma-1 receptor agonism, along with quinidine's inhibition of CYP2D6 to increase dextromethorphan's bioavailability. This suggests a potential therapeutic pathway for treating agitation in dementia, which is currently being explored in clinical trials.

What other types of research exist?

Promising novel alternatives to AVP-786 for treating agitation in dementia patients include: 1) 5-HT6 receptor antagonists like SB-742457, which have shown cognitive enhancing properties in Alzheimer's disease. 2) ANAVEX2-73, a mixed muscarinic and sigma-1 receptor agonist, which has demonstrated potential in reducing amyloid load and tau hyperphosphorylation in Alzheimer's models. These alternatives target mechanisms relevant to dementia and have shown therapeutic promise in preliminary studies.

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AVP-786 for Alzheimer's-related Agitation

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

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

Participants with a reliable caregiver who is able and willing to comply with all study procedures, including adherence to administering study drug and not administering any prohibited medications during the course of the study, and who spends a minimum of 2 hours per day for 4 days per week with the participant

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 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.

What is being tested?

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.

What are the potential side effects?

While the side effects of AVP-786 are not detailed here, similar medications often cause dizziness, headache, nausea, and sometimes more serious effects like heart problems or allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

Select...

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

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

Weight increased

Blood alkaline phosphatase increased

Myalgia

Hot flush

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 / 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 NMDA receptor antagonists, sigma-1 receptor agonists, antipsychotics, and SSRIs. Deudextromethorphan, an NMDA receptor antagonist and sigma-1 receptor agonist, helps modulate glutamate activity and neuroprotection, potentially reducing excitotoxicity and neuroinflammation. Quinidine sulfate, a CYP2D6 inhibitor, increases the bioavailability of deudextromethorphan, enhancing its therapeutic effects. Antipsychotics like risperidone and olanzapine work by blocking dopamine receptors, which can help manage psychotic symptoms and agitation. SSRIs, such as citalopram, increase serotonin levels, which can improve mood and reduce agitation. These mechanisms are crucial as they target the underlying neurochemical imbalances and symptoms associated with agitation in dementia, improving patient quality of life.

Combined treatment with memantine and galantamine-CR compared with galantamine-CR only in antidementia drug naïve patients with mild-to-moderate Alzheimer's disease.Roles of sigma-1 receptors in Alzheimer's disease.