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

Sponsor

Avanir Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02442765

Collaborator

(none)

410

Enrollment

Locations

Arms

41.9

Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Participants with agitation secondary to dementia of the Alzheimer's type. The diagnosis of probable Alzheimer's disease (AD) will be based on the "2011 Diagnostic Guidelines for Alzheimer's Disease" issued by the National Institute on Aging (NIA)-Alzheimer's Association (AA) workgroups.

Condition or Disease	Intervention/Treatment	Phase
Agitation in Patients With Dementia of the Alzheimer's Type	Drug: AVP-786 Drug: Placebo	Phase 3

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, placebo-controlled study, consisting of 12 weeks of treatment.

Approximately 380 participants will be enrolled at approximately 60 centers in North America.

Study medication will be administered orally twice-daily from Day 1 through Day 85. Screening will occur 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

410 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Jan 30, 2019

Actual Study Completion Date :

Feb 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo capsules administered twice a day over a 12-week period	Drug: Placebo
Experimental: AVP-786 (dose 1) AVP-786 dose 1; capsules administered twice a day over a 12-week period	Drug: AVP-786
Experimental: AVP-786 (dose 2) AVP-786 dose 2; capsules administered twice a day over a 12-week period	Drug: AVP-786

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo capsules administered twice a day over a 12-week period

Drug: Placebo

Experimental: AVP-786 (dose 1)

AVP-786 dose 1; capsules administered twice a day over a 12-week period

Drug: AVP-786

Experimental: AVP-786 (dose 2)

AVP-786 dose 2; capsules administered twice a day over a 12-week period

Drug: AVP-786

Outcome Measures

Primary Outcome Measures

Change from Baseline to Week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) Composite Score [Baseline; Week 12]

Secondary Outcome Measures

Change from Baseline to Week 12 in the Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC)-Agitation (Global Clinical Status of Agitation on mADCS-CGIC Scale) Score [Baseline; Week 12]
Change from Baseline to Week 12 in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score [Baseline; Week 12]
Change from Baseline to Week 12 in the NPI Caregiver Distress Score [Baseline; Week 12]
Change from Baseline to Week 12 in the NPI Aberrant Motor Behavior Domain Score [Baseline; Week 12]
Change from Baseline to Week 12 in the Zarit Burden Interview (ZBI) Score [Baseline; Week 12]
Change from Baseline to Week 12 in the NPI Irritability/Lability Domain Score [Baseline; Week 12]
Change from Baseline to Week 12 in the NPI Total Score [Baseline; Week 12]
Change from Baseline to Week 12 in the Clinical Global Impression of Severity of Illness (CGIS)-Agitation Domain Score [Baseline; Week 12]
Change from Baseline to Week 12 in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Rating [Baseline; Week 12]
Change from Baseline to Week 12 in the Patient Global Impression of Change (PGIC) Score [Baseline; Week 12]
PGIC (rated by caregiver)
Change from Baseline to Week 12 in the Dementia Quality of Life (DEMQOL) Score [Baseline; Week 12]
Change from Baseline to Week 12 in the Cornell Scale for Depression in Dementia (CSDD) Score [Baseline; Week 12]
Change from Baseline to Week 12 in the General Medical Health Rating (GMHR) Score [Baseline; Week 12]
Change from Baseline to Week 12 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score [Baseline; Week 12]
Change from Baseline to Week 12 in the Resource Utilization in Dementia (RUD) Score [Baseline; Week 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NoesisPharma, LLC	Phoenix	Arizona	United States	85032
2	Perseverance Research Center, LLC	Scottsdale	Arizona	United States	85254
3	University of California, Irvine	Irvine	California	United States	92697
4	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90806
5	NRC Research Institute	Orange	California	United States	92868
6	Pacific Research Network, Inc.	San Diego	California	United States	92103
7	VA San Diego Healthcare System	San Diego	California	United States	92103
8	HB Clinical Trials Inc.	Santa Ana	California	United States	92704
9	New Foundation Medical Group Clinical Trials	Tustin	California	United States	92780
10	Lytle and Weiss, PLLC dba Clinical Trials of the Rockies	Denver	Colorado	United States	80209
11	Connecticut Clinical Research	Cromwell	Connecticut	United States	06416
12	Coastal Connecticut Research, LLC	New London	Connecticut	United States	06320
13	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut	United States	06851
14	Neurology Offices of South Florida	Boca Raton	Florida	United States	33428
15	Coral Gables Clinical Research, Inc	Coral Gables	Florida	United States	33134
16	Optimus U Corp	Coral Gables	Florida	United States	33134
17	Quantum Laboratories, Inc.	Deerfield Beach	Florida	United States	33064
18	Direct Helpers Research Center	Hialeah	Florida	United States	33012
19	Berma Research Group	Hialeah	Florida	United States	33016
20	Galiz Research	Hialeah	Florida	United States	33016
21	Care Research Center, Inc.	Kendall	Florida	United States	33175
22	SIH Research, LLC	Kissimmee	Florida	United States	34741
23	Alzheimer's Research and Treatment Center	Lake Worth	Florida	United States	33449
24	Premier Clinical Research Institute, Inc.	Miami	Florida	United States	33122
25	Global Medical Institutes, LLC	Miami	Florida	United States	33125
26	Project 4 Research	Miami	Florida	United States	33125
27	Innova Clinical Trials	Miami	Florida	United States	33133
28	Advance Medical Research Center	Miami	Florida	United States	33135
29	Vitae Researrch Center LLC	Miami	Florida	United States	33135
30	University of Miami	Miami	Florida	United States	33136
31	Miami Jewish Health Systems, Inc.	Miami	Florida	United States	33137
32	United Health Research Corp.	Miami	Florida	United States	33144
33	Advanced Medical Center Group	Miami	Florida	United States	33145
34	Future Care Solution, LLC	Miami	Florida	United States	33165
35	International Research Associates, LLC	Miami	Florida	United States	33183
36	Naples Research, Inc.	Naples	Florida	United States	34102
37	Research Centers of America, LLC	Oakland Park	Florida	United States	33334
38	Neurology Associates of Ormond Beach	Ormond Beach	Florida	United States	32174
39	Innovation Medical Research Center	Palmetto Bay	Florida	United States	33157
40	Suncoast Neuroscience Associates, Inc.	Saint Petersburg	Florida	United States	33713
41	Roskamp Institute	Sarasota	Florida	United States	34243
42	Olympian Clinical Research	Tampa	Florida	United States	33609
43	Compass Research North, LLC	The Villages	Florida	United States	32162
44	Neurology Research Institute Palm Beach, LLC	West Palm Beach	Florida	United States	33407
45	Florida Premier Research Institute	Winter Park	Florida	United States	32789
46	NeuroTrials Research Inc.	Atlanta	Georgia	United States	30342
47	Medical Research & Health Education Foundation, Inc.	Columbus	Georgia	United States	31909
48	Behavioral Health Care Associates	Schaumburg	Illinois	United States	60194
49	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
50	MidAmerica Neuroscience Research Foundation	Lenexa	Kansas	United States	66214
51	Four Rivers Clinical Research Inc.	Paducah	Kentucky	United States	42003
52	Bedford VA Hospital	Bedford	Massachusetts	United States	01730
53	Alzheimer's Disease Center	Quincy	Massachusetts	United States	02169
54	Michigan Clinical Research Institute PC	Ann Arbor	Michigan	United States	48105
55	Bronson Neurobehavioral Health	Paw Paw	Michigan	United States	49079
56	Millennium Psychiatric Associates, LLC	Creve Coeur	Missouri	United States	63141
57	PsychCare Consultants Research	Saint Louis	Missouri	United States	63128
58	Bio Behavioral Health	Toms River	New Jersey	United States	08755
59	Dent Neurologic Institute	Amherst	New York	United States	14226
60	Integrative Clinical Trials LLC	Brooklyn	New York	United States	11229
61	Columbia University Medical Center	New York	New York	United States	10032
62	Manhattan Behavioral Medicine, PLLC	New York	New York	United States	10036
63	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York	United States	10962
64	University of Rochester Medical Center	Rochester	New York	United States	14620
65	Richmond Behavioral Associates	Staten Island	New York	United States	10312
66	Duke University Medical Center	Durham	North Carolina	United States	27710
67	Neurology and Neuroscience Associates, Inc.	Akron	Ohio	United States	44320
68	University of Cincinnati	Cincinnati	Ohio	United States	45219
69	The Ohio State University	Columbus	Ohio	United States	43210
70	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
71	Oklahoma Clinical Research Center	Oklahoma City	Oklahoma	United States	73112
72	Abington Neurological Associates, LTD	Willow Grove	Pennsylvania	United States	19090
73	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island	United States	02914
74	Roper St. Francis Healthcare	Charleston	South Carolina	United States	29401
75	Neurology Consultants of Dallas, PA	Dallas	Texas	United States	75231
76	University Texas Southwestern Medical Center	Dallas	Texas	United States	75390-8898
77	University Hills Clinical Research	Irving	Texas	United States	75062
78	Neurology Associates of Arlington	Mansfield	Texas	United States	76063
79	Ericksen Research and Development	Clinton	Utah	United States	84015
80	Neuropsychiatric Associates	Woodstock	Vermont	United States	05091

Sponsors and Collaborators

Avanir Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Avanir Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT02442765

Other Study ID Numbers:

15-AVP-786-301

First Posted:

May 13, 2015

Last Update Posted:

Feb 7, 2020

Last Verified:

Jan 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Dementia

Alzheimer Disease

Psychomotor Agitation

Study Results

No Results Posted as of Feb 7, 2020