Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

Phase 3

Terminated

Conditions: Agitation in Patients With Dementia of the Alzheimer's Type

Interventions: Drug: Placebo
Drug: AVP-786

Registration Number: NCT04464564

Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary: This study was conducted to evaluate the efficacy, safety, and tolerability of AVP-786 (deudextromethorphan hydrobromide \[d6-DM\]/quinidine sulfate \[Q\]) compared to placebo for the treatment of agitation in participants with dementia of the Alzheimer's type.

Detailed Description: Eligible participants for this study had a diagnosis of probable Alzheimer's disease (AD) and had clinically significant, moderate/severe agitation secondary to AD.

This was multicenter, randomized, double-blind, placebo-controlled study, consisting of 12 weeks of treatment. Screening occurred within 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants were randomized into the study.

241 participants were enrolled into the study.

Study medication was administered orally twice daily from Day 1 through Day 85.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 241

Inclusion Criteria

Participants with a diagnosis of probable Alzheimer's disease according to the 2011 Neuropsychiatric Inventory Agitation/Aggression (NPI-AA) working groups criteria
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 who require pharmacotherapy for the treatment of agitation per the Investigator's judgment after an evaluation of reversible factors and a course of nonpharmacological interventions
Diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation.
Participants meeting an additional predetermined blinded eligibility criterion, which will remain blinded to the clinical study site Investigators and staff
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

Exclusion Criteria

Participants with dementia predominantly of the non-Alzheimer's type (e.g., vascular dementia, frontotemporal dementia, Parkinson's disease, substance-induced dementia)
Participants with symptoms of agitation that are not secondary to Alzheimer's dementia (e.g., secondary to pain, other psychiatric disorder, or delirium)
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)
Participants with myasthenia gravis

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786 matching placebo capsules, twice a day, for 11 weeks in Period B.
AVP-786-18	AVP-786	Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786-18 (d6-DM 18 milligrams (mg)/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.
AVP-786-42.63	AVP-786	Participants who were enrolled in 1-week double-blind placebo lead-in Period A, were then randomized to receive AVP-786-42.63 (d6-DM 42.63 mg/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.

Primary Outcome Measures

Name	Time	Method
Change From the End of Period A (Week 1) to Week 10 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score	Week 1 to Week 10	The CMAI is used to assess the frequency of manifestations of agitated behaviors in elderly persons. It consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. These distinct agitation syndromes include aggressive behavior, physically nonaggressive behavior, and verbally agitated behavior. Each of the 29 items is rated on a 7-point scale of frequency (1 = never, 2 = less than once a week but still occurring, 3 = once or twice a week, 4 = several times a week, 5 = once or twice a day, 6 = several times a day, 7 = several times an hour). The ratings are based on the 2 weeks preceding assessment of the CMAI. Higher scores indicate higher frequency of agitated behaviours while lower scores indicate lower frequency of agitated behaviours.
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAE	From randomization (Week 2) up to 30 days after last dose of study drug (Up to Week 16)	An adverse event (AE) is any untoward medical occurrence or unintended change (eg, physical, psychological, or behavioral), including inter-current illness, that does not necessarily have a causal relationship with the study treatment. A serious adverse event (SAE) is any AE occurring at any dose that results in death, life-threatening experience, persistent or significant disability/incapacity, in-patient hospitalization or prolongation of hospitalization or congenital anomaly/birth defect. TEAEs are all AEs (including serious and non-serious) which started after start of double-blind study drug treatment; or if the event was continuous from baseline and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy.

Secondary Outcome Measures

Name	Time	Method
Change From the End of Period A (Week 1) to Week 10 in the Clinical Global Impression of Severity of Illness (CGIS) Score, as Related to Agitation	Week 1 to Week 10	The CGIS is an observer-rated scale that measures illness severity. The CGIS-Agitation is a 7-point (1-7) scale (1 = normal, not at all ill; 7 = among the most extremely ill patients) and assesses severity of agitation in this study. Higher scores indicate severe agitation while the lower scores indicate little or no agitation.

Trial Locations

Locations (106): Clinical Research Site #840-020
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Phoenix, Arizona, United States
Clinical Research Site #840-047
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Anaheim, California, United States
Clinical Research Site #840-090
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Costa Mesa, California, United States
Clinical Research Site #840-059
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Lafayette, California, United States
Clinical Research Site #840-048
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Lomita, California, United States
Clinical Research Site #840-095
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Long Beach, California, United States
Clinical Research Site #840-004
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Los Angeles, California, United States
Clinical Research Site #840-006
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Panorama City, California, United States
Clinical Research Site
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San Diego, California, United States
Clinical Research Site #840-070
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Apopka, Florida, United States
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Clinical Research Site #840-020
🇺🇸Phoenix, Arizona, United States