Trial Outcomes & Findings for 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 (NCT NCT04464564)

Last Updated: 2025-05-30

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

241 participants

Primary outcome timeframe

Week 1 to Week 10

Results posted on

2025-05-30

Participant Flow

Participants took part in the study at clinical sites in the North America, Latin America and Europe from 11 September 2020 to 28 June 2024.

A total of 742 participants were screened for the study, of which 241 participants were enrolled and treated with placebo in a 1-week double-blind placebo lead-in period (period A). A total of 236 participants were then randomized to receive AVP-786 (deudextromethorphan hydrobromide \[d6-DM\]/quinidine sulfate \[Q\]) or placebo in the 11-week randomization period (period B).

Participant milestones

Participant milestones
Measure	All Enrolled Participants received AVP-786 matching placebo capsules, twice a day, for 1 week in Period A.	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 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 mg/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.	AVP-786-42.63 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.
Period A (Placebo lead-in) STARTED	241	0	0	0
Period A (Placebo lead-in) COMPLETED	236	0	0	0
Period A (Placebo lead-in) NOT COMPLETED	5	0	0	0
Period B (Randomization Period) STARTED	0	76	83	77
Period B (Randomization Period) Safety Population	0	76	83	77
Period B (Randomization Period) COMPLETED	0	56	61	52
Period B (Randomization Period) NOT COMPLETED	0	20	22	25

Reasons for withdrawal

Reasons for withdrawal
Measure	All Enrolled Participants received AVP-786 matching placebo capsules, twice a day, for 1 week in Period A.	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 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 mg/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.	AVP-786-42.63 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.
Period A (Placebo lead-in) Other	5	0	0	0
Period B (Randomization Period) Adverse Event	0	1	2	8
Period B (Randomization Period) Lack of Efficacy	0	1	0	0
Period B (Randomization Period) Lost to Follow-up	0	0	0	1
Period B (Randomization Period) Study Subject Withdrawal by Parent or Guardian	0	3	3	5
Period B (Randomization Period) Study Terminated by Sponsor	0	10	10	7
Period B (Randomization Period) Withdrawal by Subject	0	2	4	1
Period B (Randomization Period) Reason not Specified	0	3	3	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=76 Participants Participants were enrolled in 1-week double-blind placebo lead-in Period A, and were then randomized to receive AVP-786 matching placebo capsules, twice a day, for 11 weeks in Period B.	AVP-786-18 n=83 Participants Participants were enrolled in 1-week double-blind placebo lead-in Period A, and were then randomized to receive AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.	AVP-786-42.63 n=77 Participants Participants were enrolled in 1-week double-blind placebo lead-in Period A, and 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.	Total n=236 Participants Total of all reporting groups
Age, Continuous	75.2 years STANDARD_DEVIATION 7.27 • n=5 Participants	76.4 years STANDARD_DEVIATION 7.50 • n=7 Participants	76.5 years STANDARD_DEVIATION 7.43 • n=5 Participants	76.0 years STANDARD_DEVIATION 7.40 • n=4 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	49 Participants n=7 Participants	55 Participants n=5 Participants	146 Participants n=4 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	34 Participants n=7 Participants	22 Participants n=5 Participants	90 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	60 Participants n=5 Participants	62 Participants n=7 Participants	57 Participants n=5 Participants	179 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	8 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	5 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	22 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	19 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	39 Participants n=5 Participants	46 Participants n=7 Participants	48 Participants n=5 Participants	133 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	35 Participants n=5 Participants	36 Participants n=7 Participants	29 Participants n=5 Participants	100 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Other	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 1 to Week 10

Population: Due to discontinuation of development of the AVP-786 compound, no data was collected and analyzed as planned for this pre-specified primary efficacy outcome measure as noted in the SAP. Only safety data was collected and analyzed

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: From randomization (Week 2) up to 30 days after last dose of study drug (Up to Week 16)

Population: Safety population included of all participants who were randomized in the double-blind period B of this study, and took at least one dose of double-blind, randomized study medication. As pre-specified in the Statistical Analysis Plan (SAP), safety data was planned to be collected only for the participants who were randomized in the double-blind period B of this study.

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.

Outcome measures

Outcome measures
Measure	Placebo n=76 Participants Participants were enrolled in 1-week double-blind placebo lead-in Period A, and were then randomized to receive AVP-786 matching placebo capsules, twice a day, for 11 weeks in Period B.	AVP-786-18 n=83 Participants Participants were enrolled in 1-week double-blind placebo lead-in Period A, and were then randomized to receive AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) capsules, twice a day, for 11 weeks in Period B.	AVP-786-42.63 n=77 Participants Participants were enrolled in 1-week double-blind placebo lead-in Period A, and 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.
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAE TEAEs	25 Participants	38 Participants	34 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAE Serious TEAEs	4 Participants	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Week 1 to Week 10

Population: Due to discontinuation of development of the AVP-786 compound, no data was collected and analyzed as planned for this pre-specified secondary efficacy outcome measure as noted in the SAP. Only safety data was collected and analyzed.

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.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 25 other events

Deaths: 1 deaths

AVP-786-18

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

AVP-786-42.63

Serious events: 5 serious events

Other events: 32 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Transparency

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 08446878522

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place