Clinical trial NCT01584440: Efficacy, Safety and Tolerability Study of AVP-923 (Dextromethorphan/Quinidine) for Treatment of Symptoms of Agitation in Participants With Alzheimer's Disease
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Agitation
Alzheimer's Disease
Keywords: AVP-923-20
AVP-923-30
AVP-923
Dextromethorphan
Quinidine
Neuropsychiatric Inventory
Aggression
Efficacy
Safety
Lead sponsor: Avanir Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-04-25
Enrollment: 220
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 participants with Alzheimer's Disease (AD).

Detailed description: Eligible participants 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 participants 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 participants will be randomized into the study.

Eligibility criteria: Key Inclusion Criteria:

Diagnosis of probable Alzheimer's disease (AD).

The participant 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 participant 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 participant for a minimum of 4 hours on 4 separate days per week.

Key Exclusion Criteria:

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

Participant 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).

Participant with myasthenia gravis.

Primary outcomes:
measure: Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
Secondary outcomes:
measure: Number of Participants With the Indicated Type of Adverse Event
timeFrame: up to Week 10
measure: Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57
timeFrame: Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57
measure: Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline)
timeFrame: Day 36 (Stage 2 Baseline); Day 70
measure: Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
timeFrame: Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70
measure: Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
timeFrame: Day 1 (Stage 1 Baseline); Day 70
measure: Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use
timeFrame: up to Week 10
measure: Number of Participants Using Rescue Medications
timeFrame: up to Week 10
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Sun City
country: United States
state: Arizona
city: Fresno
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Sherman Oaks
country: United States
state: California
city: Temecula
country: United States
state: California
city: Boynton Beach
country: United States
state: Florida
city: Deerfield Beach
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Sunrise
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Weston
country: United States
state: Florida
city: Elk Grove Village
country: United States
state: Illinois
city: Las Vegas
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: Summit
country: United States
state: New Jersey
city: Toms River
country: United States
state: New Jersey
city: Orangeburg
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: White Plains
country: United States
state: New York
city: Centerville
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Lakewood
country: United States
state: Ohio
city: Allentown
country: United States
state: Pennsylvania
city: Reading
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Bennington
country: United States
state: Vermont
city: Spokane
country: United States
state: Washington
Study officials:
References:
citation: 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.