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

Tracking Information
First Submitted Date ICMJE	April 23, 2012
First Posted Date ICMJE	April 25, 2012
Last Update Posted Date	January 11, 2018
Study Start Date ICMJE	June 2012
Actual Primary Completion Date	July 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 18, 2014)	Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ]; Primary Endpoint: Agitation/Aggression Domain of NPI
Original Primary Outcome Measures ICMJE; (submitted: April 24, 2012)	Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ]
Change History	Complete list of historical versions of study NCT01584440 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 18, 2014)	Safety and Tolerability [ Time Frame: 10 weeks ]Standard Measurements (e.g. AEs, ECG, Labs, PE and Neuro Exam); Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ]Total NPI; Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ]Caregiver Distress for NPI Domains; Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ]NPI-4A (Composite of 4 NPI Domains); Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ]NPI-4D (Composite of 4 NPI Domains); Neuropsychiatric Inventory (NPI) [ Time Frame: 10 weeks ]Individual Domains of NPI; ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Rating) [ Time Frame: 10 weeks ]Agitation and Overall; PGIC Patient Global Impression of Change (PGI-C) [ Time Frame: 10 weeks ]Agitation (Rated by Caregiver); QoL-AD (Quality of Life - Alzheimer's Disease measure) [ Time Frame: 10 weeks ]; ADCS-ADL (Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory) [ Time Frame: 10 weeks ]; CSI (Caregiver Strain Index) [ Time Frame: 10 weeks ]; CSDD (Cornell Scale for Depression in Dementia) [ Time Frame: 10 weeks ]; (MMSE) Mini-Mental State Examination [ Time Frame: 10 weeks ]
Original Secondary Outcome Measures ICMJE; (submitted: April 24, 2012)	ADCS-ADL [ Time Frame: 10 weeks ]; PGIC [ Time Frame: 10 weeks ]; ADCS-CGIC [ Time Frame: 10 weeks ]; QoL-AD [ Time Frame: 10 weeks ]; CSDD [ Time Frame: 10 weeks ]; CSI [ Time Frame: 10 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy, Safety and Tolerability Study of AVP-923 (Dextromethorphan/Quinidine) for Treatment of Symptoms of Agitation in Alzheimer's Patients
Official Title ICMJE	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.
Brief Summary	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).
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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Agitation; Alzheimer's Disease
Intervention ICMJE	Drug: AVP-923 (dextromethorphan/quinidine) AVP-923 capsules administered twice a day over a 10-week period; Drug: Placebo Placebo capsules administered twice a day over a 10-week period
Study Arms	Placebo Comparator: Placebo Intervention: Drug: Placebo; Experimental: AVP-923 Intervention: Drug: AVP-923 (dextromethorphan/quinidine)
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: September 18, 2014)	220
Original Estimated Enrollment ICMJE; (submitted: April 24, 2012)	200
Actual Study Completion Date	September 2014
Actual Primary Completion Date	July 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	50 Years to 90 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01584440
Other Study ID Numbers ICMJE	12-AVR-131
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Avanir Pharmaceuticals
Study Sponsor ICMJE	Avanir Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Avanir Pharmaceuticals
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP