Efficacy, Safety and Tolerability Study of AVP-923 (Dextromethorphan/Quinidine) for Treatment of Symptoms of Agitation in Alzheimer's Patients - Full Text View

Purpose

The objectives of the study are to evaluate the safety, tolerability and efficacy of AVP-923 compared to placebo, for the treatment of symptoms of agitation in patients with Alzheimer's Disease (AD).

Condition	Intervention	Phase
Agitation Alzheimer's Disease	Drug: AVP-923 (dextromethorphan/quinidine) Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 2, Randomized, Double-dummy, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of AVP-923 (Dextromethorphan/Quinidine) for the Treatment of Symptoms of Agitation in Patients With Alzheimer's Disease.

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease

Drug Information available for: Dextromethorphan hydrobromide Dextromethorphan Quinidine gluconate Quinidine sulfate Nuedexta

Genetic and Rare Diseases Information Center resources: Familial Alzheimer Disease

U.S. FDA Resources

Further study details as provided by Avanir Pharmaceuticals:

Primary Outcome Measures:

Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Primary Endpoint: Agitation/Aggression Domain of NPI

Secondary Outcome Measures:

Safety and Tolerability [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
Standard Measurements (e.g. AEs, ECG, Labs, PE and Neuro Exam)
Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Total NPI
Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Caregiver Distress for NPI Domains
Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
NPI-4A (Composite of 4 NPI Domains)
Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
NPI-4D (Composite of 4 NPI Domains)
Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Individual Domains of NPI
ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Rating) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Agitation and Overall
PGIC Patient Global Impression of Change (PGI-C) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Agitation (Rated by Caregiver)
QoL-AD (Quality of Life - Alzheimer's Disease measure) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
ADCS-ADL (Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
CSI (Caregiver Strain Index) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
CSDD (Cornell Scale for Depression in Dementia) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
(MMSE) Mini-Mental State Examination [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]


Enrollment:	220
Study Start Date:	June 2012
Study Completion Date:	September 2014
Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo	Drug: Placebo Placebo capsules administered twice a day over a 10-week period
Experimental: AVP-923	Drug: AVP-923 (dextromethorphan/quinidine) AVP-923 capsules administered twice a day over a 10-week period

Detailed Description:

Eligible patients for this study must have a diagnosis of probable AD and must have clinically meaningful agitation secondary to AD.

This is a multicenter, randomized, double-dummy, double-blind, placebo-controlled study, consisting of 10 weeks of treatment.

Up to 200 patients will be enrolled at approximately 30-40 centers in the US.

Study medication will be administered orally twice-daily from Day 1 through Day 70. Screening must occur within within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible patients will be randomized into the study.

Eligibility


Ages Eligible for Study:	50 Years to 90 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Key Inclusion Criteria:

Diagnosis of probable Alzheimer's disease (AD).

The patient has clinically significant symptoms of agitation secondary to AD, that interfere with daily routine and for which a prescription medication is deemed indicated, in the opinion of the investigator.

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

CGI-S score is ≥ 4 (moderately ill) at screening and baseline.

Mini Mental State Examination (MMSE) score at screening between 8 and 28 (inclusive).

Caregiver who is able and willing to comply with all required study procedures, ensuring that the patient attends all study visits and takes the study medication as instructed. In order to qualify as a caregiver for this study, the individual should spend time with the patient for a minimum of 4 hours on 4 separate days per week.

Key Exclusion Criteria:

Patient has other type of dementia (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia).

Patients 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, certain cardiac conduction abnormalities including QTc prolongation, or unstable valvular heart disease).

Patients with myasthenia gravis.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01584440

Show 44 Study Locations

Sponsors and Collaborators

Avanir Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, De La Gandara JE, Agronin M, Davis CS, Nguyen U, Shin P, Tariot PN, Siffert J. Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA. 2015 Sep 22-29;314(12):1242-54. doi: 10.1001/jama.2015.10214.


Responsible Party:	Avanir Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01584440 History of Changes
Other Study ID Numbers:	12-AVR-131
Study First Received:	April 23, 2012
Last Updated:	September 18, 2014
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Alzheimer Disease Psychomotor Agitation Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders Dyskinesias Neurologic Manifestations Psychomotor Disorders Neurobehavioral Manifestations Signs and Symptoms	Dextromethorphan Quinidine Quinidine gluconate Antitussive Agents Respiratory System Agents Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Adrenergic alpha-Antagonists Adrenergic Antagonists Adrenergic Agents Anti-Arrhythmia Agents Antimalarials

ClinicalTrials.gov processed this record on September 29, 2016