CompletedPhase 3Results posted

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

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deuterated [d6]-Dextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type

Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Asset

AVP-786

Listed sites

126

Recruiting sites

Enrollment

387

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 6-26•Study partner/caregiver required

Primary endpoint

•Stage 1 and Stage 2

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID15-AVP-786-301

NCT IDNCT02442765

Timeline

Milestones

Study first posted2015-05-13estimated

Study start2015-07-23actual

Primary completion2019-01-30actual

Study completion2019-02-27actual

Last update posted2023-02-13actual

Results first posted2023-02-13actual

Assets

Drug assets

AVP-786

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Diagnosis of probable Alzheimer's Disease (AD) according to the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) working groups criteria

•The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization

•The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation

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

•Clinical Global Impression of Severity of Illness (CGIS) score assessing Agitation is >= 4 (moderately ill) at screening and baseline

•Mini-Mental State Examination (MMSE) score is between 6 and 26 (inclusive) at screening and baseline

•Caregiver who is able and willing to comply with all required study procedures. In order to qualify as a reliable informant (i.e., caregiver) capable of assessing changes in participant's condition during the study, the individual must spend a minimum of 2 hours per day for 4 days per week with the participant

Exclusion criteria

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

•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, poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)

•Participant with myasthenia gravis

Endpoints (42)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Caregiver / quality of life

Global cognition

Other (unclassified)

Global cognition

2 endpoints

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=131 Participants	25.8	10.10
Change from Baseline at Week 6n=130 Participants	-0.5	4.46
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=68 Participants	26.2	8.99
Change from Baseline at Week 6n=68 Participants	-2.0	4.28
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=71 Participants	25.3	8.88
Change from Baseline at Week 6n=71 Participants	-0.5	4.72
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=25 Participants	26.9	9.56
Change from Baseline at Week 12n=25 Participants	-0.8	5.05
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=27 Participants	27.0	9.27
Change from Baseline at Week 12n=27 Participants	0.3	4.95
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=32 Participants	25.3	10.91
Change from Baseline at Week 12n=32 Participants	0.1	5.47

Least Squares Mean Difference-1.695% CI-2.9 - -0.3p=0.018ANCOVA

Least Squares Mean Difference0.095% CI-1.3 - 1.3p=0.956ANCOVA

Least Squares Mean Difference1.195% CI-1.8 - 4.0p=0.451ANCOVA

Least Squares Mean Difference0.995% CI-1.9 - 3.7p=0.519ANCOVA

SPCD OLS weighted z-statistic-0.72p=0.471ANCOVA

SPCD OLS weighted z-statistic0.50p=0.618ANCOVA

Behavior / neuropsychiatric

26 endpoints

Primary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

change from baseline, improvement

Primary/registry result

Stage 1 and Stage 2: Change From Baseline in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=188 Participants	73.9	22.23
Change from Baseline at Week 6n=180 Participants	-10.7	15.29
Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 1 Baselinen=92 Participants	72.3	23.08
Change from Baseline at Week 6n=85 Participants	-13.9	16.70
Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 1 Baselinen=97 Participants	71.7	23.57
Change from Baseline at Week 6n=94 Participants	-10.3	13.54
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	66.0	24.71
Change from Baseline at Week 12n=40 Participants	-1.6	11.08
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=40 Participants	68.9	20.79
Change from Baseline at Week 12n=40 Participants	-5.6	11.78
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	65.3	19.36
Change from Baseline at Week 12n=44 Participants	-4.9	12.13

Least Squares Mean Difference-4.095% CI-7.4 - -0.6p=0.021mixed model repeated measures (MMRM)

Least Squares Mean Difference-0.695% CI-3.9 - 2.7p=0.731MMRM

Least Squares Mean Difference-3.595% CI-8.4 - 1.4p=0.157MMRM

Least Squares Mean Difference-3.695% CI-8.4 - 1.3p=0.150MMRM

MMRM weighted z-statistic-2.65p=0.008MMRM

MMRM weighted z-statistic-1.26p=0.208MMRM

Secondary/protocol endpoint

Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12

Time frame:Stage 1 Week 6; Stage 2 Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

categorical status, descriptive

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

change from baseline, improvement

Secondary/registry result

Least Squares Mean Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation Score at Week 6 and Week 12

Time frame:Stage 1 Week 6; Stage 2 Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
Stage 1: PlaceboStage 1 Week 6n=184 Participants	3.4	1.13
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Week 6n=90 Participants	3.2	1.24
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Week 6n=96 Participants	3.3	1.12
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Week 12n=40 Participants	3.9	0.18
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Week 12n=40 Participants	3.3	0.18
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Week 12n=42 Participants	3.5	0.17

Least Squares Mean Difference-0.195% CI-0.4 - 0.1p0.331ANCOVA

Least Squares Mean Difference-0.195% CI-0.4 - 0.2p0.400ANCOVA

Least Squares Mean Difference-0.695% CI-1.1 - -0.1p0.014ANCOVA

Least Squares Mean Difference-0.495% CI-0.9 - 0.1p0.145ANCOVA

SPCD OLS weighted z-statistic-2.51p0.012ANCOVA

SPCD OLS weighted z-statistic-1.66p0.097ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=191 Participants	7.1	2.39
Change from Baseline at Week 6n=183 Participants	-1.8	3.58
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=94 Participants	6.5	1.94
Change from Baseline at Week 6n=87 Participants	-2.0	3.03
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=97 Participants	7.2	2.42
Change from Baseline at Week 6n=94 Participants	-2.1	2.94
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	6.9	2.84
Change from Baseline at Week 12n=39 Participants	-1.7	3.00
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=41 Participants	6.3	2.71
Change from Baseline at Week 12n=41 Participants	-0.8	3.15
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	6.3	2.81
Change from Baseline at Week 12n=41 Participants	-0.9	3.35

Least Squares Mean Difference-0.595% CI-1.3 - 0.2p=0.182MMRM

Least Squares Mean Difference-0.395% CI-1.1 - 0.4p=0.390MMRM

Least Squares Mean Difference0.595% CI-0.8 - 1.7p=0.462MMRM

Least Squares Mean Difference0.495% CI-0.8 - 1.6p=0.528MMRM

MMRM weighted z-statistic-0.39p=0.695ANCOVA

MMRM weighted z-statistic-0.12p=0.904ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the NPI Caregiver Distress Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=164 Participants	18.87	9.026
Change from Baseline at Week 6n=147 Participants	-4.31	7.979
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=77 Participants	18.90	9.266
Change from Baseline at Week 6n=69 Participants	-5.48	8.559
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=85 Participants	18.88	10.015
Change from Baseline at Week 6n=75 Participants	-4.83	7.736
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=39 Participants	17.33	9.010
Change from Baseline at Week 12n=37 Participants	-0.73	6.533
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=38 Participants	15.95	7.241
Change from Baseline at Week 12n=33 Participants	-1.67	5.666
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=43 Participants	16.89	7.416
Change from Baseline at Week 12n=36 Participants	0.44	7.265

Least Squares Mean Difference-1.295% CI-3.2 - 0.8p=0.247MMRM

Least Squares Mean Difference-0.495% CI-2.3 - 1.6p=0.721MMRM

Least Squares Mean Difference-1.295% CI-4.3 - 1.8p=0.419MMRM

Least Squares Mean Difference0.995% CI-2.0 - 3.9p=0.534MMRM

MMRM weighted z-statistic-1.40p=0.163ANCOVA

MMRM weighted z-statistic0.19p=0.851ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the NPI Aberrant Motor Behavior Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=191 Participants	5.1	3.94
Change from Baseline at Week 6 Stage 2 Baselinen=183 Participants	-0.9	3.62
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=94 Participants	4.9	3.77
Change from Baseline at Week 6 Stage 2 Baselinen=87 Participants	-1.6	3.74
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=97 Participants	5.1	4.07
Change from Baseline at Week 6 Stage 2 Baselinen=94 Participants	-0.7	3.86
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	5.2	3.79
Change from Baseline at Week 12n=39 Participants	-0.4	2.16
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=41 Participants	4.0	3.87
Change from Baseline at Week 12n=41 Participants	0.6	3.24
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	4.3	4.32
Change from Baseline at Week 12n=41 Participants	1.1	3.54

Least Squares Mean Difference-0.695% CI-1.4 - 0.2p=0.146MMRM

Least Squares Mean Difference0.395% CI-0.4 - 1.1p=0.399MMRM

Least Squares Mean Difference0.795% CI-0.6 - 2.0p=0.283MMRM

Least Squares Mean Difference1.295% CI-0.1 - 2.5p=0.065MMRM

MMRM weighted z-statistic-0.22p=0.829ANCOVA

MMRM weighted z-statistic1.94p=0.052ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the Zarit Burden Interview (ZBI) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=190 Participants	30.9	16.19
Change from Baseline at Week 6n=190 Participants	-1.4	8.22
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=94 Participants	30.0	16.96
Change from Baseline at Week 6n=94 Participants	-2.0	8.44
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=97 Participants	33.0	16.68
Change from Baseline at Week 6n=97 Participants	-2.7	9.49
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	31.5	15.24
Change from Baseline at Week 12n=40 Participants	-1.1	7.65
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=41 Participants	32.0	16.57
Change from Baseline at Week 12n=41 Participants	1.4	8.71
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	28.6	16.76
Change from Baseline at Week 12n=44 Participants	-0.5	7.05

Least Squares Mean Difference-0.795% CI-2.7 - 1.4p=0.530ANCOVA

Least Squares Mean Difference-1.095% CI-3.1 - 1.0p=0.326ANCOVA

Least Squares Mean Difference2.595% CI-0.8 - 5.9p=0.135ANCOVA

Least Squares Mean Difference0.295% CI-3.1 - 3.5p=0.895ANCOVA

SPCD OLS weighted Z-statistic0.67p=0.502ANCOVA

SPCD OLS weighted Z-statistic-0.58p=0.564ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the NPI Irritability/Lability Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=191 Participants	5.1	3.33
Change from Baseline at Week 6n=183 Participants	-1.1	3.84
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=94 Participants	5.1	3.62
Change from Baseline at Week 6n=87 Participants	-1.9	3.71
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=97 Participants	5.2	3.39
Change from Baseline at Week 6n=94 Participants	-1.4	3.62
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	4.5	3.99
Change from Baseline at Week 12n=39 Participants	0.2	3.19
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=41 Participants	5.3	3.54
Change from Baseline at Week 12n=41 Participants	-1.3	3.88
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	5.2	3.64
Change from Baseline at Week 12n=41 Participants	-0.9	3.45

Least Squares Mean Difference-0.895% CI-1.6 - 0.0p=0.061MMRM

Least Squares Mean Difference-0.395% CI-1.1 - 0.5p=0.400MMRM

Least Squares Mean Difference-1.195% CI-2.4 - 0.3p=0.115MMRM

Least Squares Mean Difference-0.895% CI-2.1 - 0.6p=0.264MMRM

MMRM weighted z-statistic-2.44p=0.015ANCOVA

MMRM weighted z-statistic-1.40p=0.163ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the NPI Total Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=191 Participants	40.2	17.95
Change from Baseline at Week 6n=183 Participants	-9.2	17.41
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=94 Participants	39.4	18.93
Change from Baseline at Week 6n=87 Participants	-13.2	17.99
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=97 Participants	40.1	19.98
Change from Baseline at Week 6n=94 Participants	-10.6	16.09
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	39.2	22.47
Change from Baseline at Week 12n=39 Participants	-5.1	14.03
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=41 Participants	34.7	14.16
Change from Baseline at Week 12n=41 Participants	-4.4	12.92
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	34.6	16.93
Change from Baseline at Week 12n=41 Participants	-0.1	18.82

Least Squares Mean Difference-3.995% CI-7.8 - -0.0p=0.050MMRM

Least Squares Mean Difference-1.695% CI-5.4 - 2.2p=0.412MMRM

Least Squares Mean Difference-1.095% CI-7.8 - 5.8p=0.775MMRM

Least Squares Mean Difference3.395% CI-3.5 - 10.1p=0.333MMRM

MMRM weighted z-statistic-1.50p=0.133ANCOVA

MMRM weighted z-statistic0.22p=0.829ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=191 Participants	4.5	0.64
Change from Baseline at Week 6n=191 Participants	-0.5	0.78
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=94 Participants	4.3	0.49
Change from Baseline at Week 6n=94 Participants	-0.7	0.97
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=97 Participants	4.4	0.70
Change from Baseline at Week 6n=97 Participants	-0.7	1.04
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	4.4	0.87
Change from Baseline at Week 12n=40 Participants	-0.2	0.58
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=41 Participants	4.2	0.77
Change from Baseline at Week 12n=41 Participants	-0.4	0.70
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	4.1	0.77
Change from Baseline at Week 12n=44 Participants	-0.3	1.01

Least Squares Mean Difference-0.295% CI-0.4 - 0.0p=0.118ANCOVA

Least Squares Mean Difference-0.195% CI-0.4 - 0.1p=0.191ANCOVA

Least Squares Mean Difference-0.295% CI-0.5 - 0.1p=0.225ANCOVA

Least Squares Mean Difference-0.295% CI-0.5 - 0.1p=0.227ANCOVA

SPCD OLS weighted z-statistic-1.97p=0.049ANCOVA

SPCD OLS weighted z-statistic-1.78p=0.075ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating at Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
Stage 1: PlaceboStage 1 Week 6n=183 Participants	3.7	0.11
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Week 6n=90 Participants	3.5	0.14
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Week 6n=96 Participants	3.6	0.13
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Week 12n=40 Participants	4.0	0.17
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Week 12n=40 Participants	3.6	0.17
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Week 12n=42 Participants	3.7	0.16

Least Squares Mean Difference-0.195% CI-0.4 - 0.1p=0.364ANCOVA

Least Squares Mean Difference-0.195% CI-0.4 - 0.2p=0.427ANCOVA

Least Squares Mean Difference-0.495% CI-0.9 - 0.1p=0.098ANCOVA

Least Squares Mean Difference-0.395% CI-0.8 - 0.1p=0.168ANCOVA

SPCD OLS weighted z-statistic-1.86p=0.063ANCOVA

SPCD OLS weighted z-statistic-1.57p=0.115ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Patient Global Impression of Change (PGIC) Score at Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

categorical status, descriptive

Posted result

Group	Value (least_squares_mean), units on a scale	Standard error
Stage 1: PlaceboStage 1 Week 6n=185 Participants	3.4	0.12
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Week 6n=90 Participants	3.0	0.15
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Week 6n=96 Participants	3.1	0.14
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Week 12n=40 Participants	3.6	0.20
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Week 12n=41 Participants	3.1	0.20
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Week 12n=44 Participants	3.3	0.19

Least Squares Mean Difference-0.495% CI-0.6 - -0.1p=0.014ANCOVA

Least Squares Mean Difference-0.295% CI-0.5 - 0.1p=0.111ANCOVA

Least Squares Mean Difference-0.595% CI-1.1 - 0.0p=0.062ANCOVA

Least Squares Mean Difference-0.395% CI-0.8 - 0.3p=0.305ANCOVA

SPCD OLS weighted z-statistic-3.01p=0.003ANCOVA

SPCD OLS weighted z-statistic-1.79p=0.073ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the Dementia Quality of Life (DEMQOL) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=133 Participants	85.7	10.63
Change from Baseline at Week 6n=133 Participants	2.3	8.26
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=69 Participants	82.9	10.22
Change from Baseline at Week 6n=69 Participants	3.5	8.57
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=72 Participants	84.0	11.98
Change from Baseline at Week 6n=72 Participants	4.4	10.79
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=24 Participants	86.8	9.96
Change from Baseline at Week 12n=24 Participants	2.5	5.40
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=30 Participants	90.0	9.51
Change from Baseline at Week 12n=30 Participants	3.1	9.52
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=32 Participants	87.8	10.72
Change from Baseline at Week 12n=32 Participants	1.1	13.06

Least Squares Mean Difference0.195% CI-2.2 - 2.5p=0.909ANCOVA

Least Squares Mean Difference1.495% CI-0.9 - 3.8p=0.226ANCOVA

Least Squares Mean Difference2.195% CI-2.9 - 7.1p=0.405ANCOVA

Least Squares Mean Difference-0.995% CI-5.8 - 4.0p=0.714ANCOVA

SPCD OLS weighted z-statistic0.75p=0.456ANCOVA

SPCD OLS weighted z-statistic0.42p=0.678ANCOVA

Secondary/registry result

Stage 1 and Stage 2: Change From Baseline in the Cornell Scale for Depression in Dementia (CSDD) Score to Week 6 and Week 12

Time frame:Stage 1: Baseline, Week 6; Stage 2: Baseline (Week 6), Week 12

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
Stage 1: PlaceboStage 1 Baselinen=191 Participants	6.2	2.24
Change from Baseline at Week 6n=191 Participants	-0.3	3.01
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgStage 1 Baselinen=94 Participants	6.3	2.11
Change from Baseline at Week 6n=94 Participants	-0.7	3.09
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgStage 1 Baselinen=97 Participants	6.4	2.19
Change from Baseline at Week 6n=97 Participants	-0.5	2.93
Stage 1: Placebo Non-responders to Stage 2: PlaceboStage 2 Baselinen=40 Participants	6.6	3.89
Change from Baseline at Week 12n=40 Participants	-0.4	2.56
Stage 1: Placebo Non-responders to Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Stage 2 Baselinen=41 Participants	5.9	2.78
Change from Baseline at Week 12n=41 Participants	-0.5	2.36
Stage 1: Placebo Non-responders to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Stage 2 Baselinen=44 Participants	6.8	2.84
Change from Baseline at Week 12n=44 Participants	-0.3	3.09

Least Squares Mean Difference-0.495% CI-1.1 - 0.3p=0.278ANCOVA

Least Squares Mean Difference-0.195% CI-0.8 - 0.6p=0.817ANCOVA

Least Squares Mean Difference-0.495% CI-1.4 - 0.7p=0.500ANCOVA

Least Squares Mean Difference0.195% CI-0.9 - 1.2p=0.795ANCOVA

SPCD OLS weighted z-statistic-1.25p=0.213ANCOVA

SPCD OLS weighted z-statistic0.02p=0.985ANCOVA

Caregiver / quality of life

12 endpoints

Secondary/protocol endpoint

Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals

Time frame:Stage 1: Week 6

threshold achievement, improvement

Secondary/protocol endpoint

Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals

Time frame:Stage 2: Week 12

threshold achievement, improvement

Secondary/protocol endpoint

Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant

Time frame:Stage 1: Week 6

event count, event

Secondary/protocol endpoint

Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant

Time frame:Stage 2: Week 12

event count, event

Secondary/protocol endpoint

Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant

Time frame:Stage 1: Week 6

event count, event

Secondary/protocol endpoint

12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant

Time frame:12-Week Parallel Group: Week 12

event count, event

Secondary/registry result

Stage 1: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals

Time frame:Stage 1: Week 6

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Stage 1: PlaceboCaregivers Who Reported that their Responsibilities Affected Their Workn=74 Participants	33.8	-
Caregivers Who Visited Health Care Professionalsn=185 Participants	42.2	-
Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Caregivers Who Reported that their Responsibilities Affected Their Workn=35 Participants	22.9	-
Caregivers Who Visited Health Care Professionalsn=90 Participants	31.1	-
Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Caregivers Who Reported that their Responsibilities Affected Their Workn=38 Participants	34.2	-
Caregivers Who Visited Health Care Professionalsn=96 Participants	44.8	-

Secondary/registry result

Stage 2: Resource Utilization in Dementia (RUD): Percentage of Caregiver Who Reported That Their Responsibilities Affected Their Work and Who Visited Health Care Professionals

Time frame:Stage 2: Week 12

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Stage 2: Placebo/PlaceboCaregivers Who Reported that their Responsibilities Affected Their Workn=25 Participants	44.0	-
Caregivers Who Visited Health Care Professionalsn=58 Participants	43.1	-
Stage 1: Placebo to: Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mgCaregivers Who Reported that their Responsibilities Affected Their Workn=59 Participants	28.6	-
Caregivers Who Visited Health Care Professionalsn=59 Participants	30.5	-
Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mgCaregivers Who Reported that their Responsibilities Affected Their Workn=60 Participants	36.4	-
Caregivers Who Visited Health Care Professionalsn=58 Participants	29.3	-
Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) to: Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Caregivers Who Reported that their Responsibilities Affected Their Workn=33 Participants	24.2	-
Caregivers Who Visited Health Care Professionalsn=86 Participants	26.7	-
Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Caregivers Who Reported that their Responsibilities Affected Their Workn=34 Participants	35.3	-
Caregivers Who Visited Health Care Professionalsn=92 Participants	37.0	-

Secondary/registry result

Stage 1: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant

Time frame:Stage 1: Week 6

event count, event

Posted result

Group	Value (median), hours	Reported bounds
Stage 1: PlaceboWeek 6 (Q1)n=171 Participants	2.0	-0 - 20
Week 6 (Q2)n=171 Participants	4.0	-1 - 24
Week 6 (Q3)n=171 Participants	3.0	-0 - 24
Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Week 6 (Q1)n=84 Participants	2.0	-0 - 24
Week 6 (Q2)n=84 Participants	4.0	-0 - 18
Week 6 (Q3)n=84 Participants	2.0	-0 - 24
Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Week 6 (Q1)n=90 Participants	2.0	-0 - 15
Week 6 (Q2)n=90 Participants	4.0	-1 - 15
Week 6 (Q3)n=90 Participants	2.8	-0 - 24

Secondary/registry result

Stage 2: Resource Utilization in Dementia (RUD): Number of Hours Per Day the Caregiver Spent Assisting the Participant

Time frame:Stage 2: Week 12

event count, event

Posted result

Group	Value (median), hours	Reported bounds
Stage 1: Placebo to Stage 2: PlaceboWeek 12 (Q1)n=54 Participants	1.5	-0 - 15
Week 12 (Q2)n=54 Participants	4.0	-0 - 16
Week 12 (Q3)n=54 Participants	1.0	-0 - 19
Stage 1: Placebo to Stage 2: AVP-786 18 mgWeek 12 (Q1)n=55 Participants	2.0	-0 - 7
Week 12 (Q2)n=55 Participants	4.0	-0 - 24
Week 12 (Q3)n=55 Participants	3.0	-0 - 24
Stage 1: Placebo to Stage 2: AVP-786 28 mgWeek 12 (Q1)n=53 Participants	2.0	-0 - 12
Week 12 (Q2)n=53 Participants	4.0	-0 - 24
Week 12 (Q3)n=53 Participants	3.0	-0 - 20
Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg) to: Stage 2: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)Week 12 (Q1)n=81 Participants	2.0	-0 - 10
Week 12 (Q2)n=81 Participants	4.0	-0 - 17
Week 12 (Q3)n=81 Participants	2.0	-0 - 24
Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Week 12 (Q1)n=87 Participants	2.0	-0 - 14
Week 12 (Q2)n=87 Participants	4.0	-0 - 15
Week 12 (Q3)n=87 Participants	2.0	-0 - 18

Secondary/registry result

Stage 1: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant

Time frame:Stage 1: Week 6

event count, event

Posted result

Group	Value (median), days	Reported bounds
Stage 1: PlaceboWeek 6 (Q1)n=171 Participants	30.0	-0 - 30
Week 6 (Q2)n=171 Participants	30.0	-0 - 30
Week 6 (Q3)n=171 Participants	30.0	-0 - 30
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mgWeek 6 (Q1)n=84 Participants	30.0	-0 - 30
Week 6 (Q2)n=84 Participants	30.0	-0 - 39
Week 6 (Q3)n=84 Participants	30.0	-0 - 30
Stage 1: AVP-786-28 d6-DM 28 mg/Q 4.9 mgWeek 6 (Q1)n=90 Participants	30.0	-0 - 30
Week 6 (Q2)n=90 Participants	30.0	-4 - 30
Week 6 (Q3)n=90 Participants	30.0	-0 - 30

Secondary/registry result

12-Week Parallel Group: Resource Utilization in Dementia (RUD) Score: Number of Days the Caregiver Spent Assisting the Participant

Time frame:12-Week Parallel Group: Week 12

event count, event

Posted result

Group	Value (median), days	Reported bounds
Stage 1: Placebo to Stage 2: PlaceboWeek 12 (Q1)n=54 Participants	30.0	-0 - 30
Week 12 (Q2)n=54 Participants	30.0	-0 - 30
Week 12 (Q3)n=54 Participants	30.0	-0 - 30
Stage 1: Placebo to Stage 2: AVP-786 18 mgWeek 12 (Q1)n=81 Participants	30.0	-0 - 30
Week 12 (Q2)n=81 Participants	30.0	-0 - 30
Week 12 (Q3)n=81 Participants	30.0	-0 - 30
Stage 1: Placebo to Stage 2: AVP-786 28 mgWeek 12 (Q1)n=87 Participants	30.0	-0 - 30
Week 12 (Q2)n=87 Participants	30.0	-0 - 30
Week 12 (Q3)n=87 Participants	30.0	-0 - 30

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score

Time frame:Baseline; Week 12

threshold achievement, improvement

Secondary/registry result/low confidence

Stage 2: Percentage of Participants With General Medical Health Rating (GMHR) Score

Time frame:Baseline; Week 12

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	Reported bounds
Stage 1: Placebo to Stage 2: PlaceboExcellent to very goodn=62 Participants	22.6	-
Goodn=62 Participants	59.7	-
Fairn=62 Participants	11.3	-
Poorn=62 Participants	0	-
Missingn=62 Participants	6.5	-
Stage 1: Placebo to: Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mgExcellent to very goodn=64 Participants	20.3	-
Goodn=64 Participants	64.1	-
Fairn=64 Participants	7.8	-
Poorn=64 Participants	0	-
Missingn=64 Participants	7.8	-
Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mgExcellent to very goodn=65 Participants	13.8	-
Goodn=65 Participants	58.5	-
Fairn=65 Participants	16.9	-
Poorn=65 Participants	0	-
Missingn=65 Participants	10.8	-
Stage 1: AVP-786-18 d6-DM 18 mg/Q 4.9 mg to Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mgExcellent to very goodn=94 Participants	20.2	-
Goodn=94 Participants	58.5	-
Fairn=94 Participants	13.8	-
Poorn=94 Participants	0	-
Missingn=94 Participants	7.4	-
Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg) to Stage 2: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)Excellent to very goodn=97 Participants	20.6	-
Goodn=97 Participants	62.9	-
Fairn=97 Participants	11.3	-
Poorn=97 Participants	0	-
Missingn=97 Participants	5.2	-

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.