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

NCT02442765 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 15-AVP-786-301
• Study Type: interventional
• Target: 387
• Locations: 6 countries
• Sites: 126

Brief Summary

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

Conditions

Agitation in Patients With Dementia of the Alzheimer's Type

Keywords

Agitation; Dementia; Alzheimer's disease

Outcome Measures

Primary Outcomes (1)

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

  The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency: 1, never; 2, less than once a week; 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 CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.

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

Secondary Outcomes (20)

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

  Stage 1 Week 6; Stage 2 Week 12

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

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

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

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

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

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

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

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

Study Arms (8)

Stage 1: Placebo

PLACEBO COMPARATOR

Participants received matching placebo orally twice daily (BID) for 6 weeks (Days 1-42) in Stage 1. Participants who completed Stage 1 were eligible to Participate in Stage 2.

Drug: Placebo

Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg)

EXPERIMENTAL

Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for the remaining 5 weeks (Days 8-42). Participants who completed Stage 1 were eligible to participate in Stage 2.

Drug: AVP-786

Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg)

EXPERIMENTAL

Participants received AVP-786-18 mg orally QD in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg orally BID for 2 weeks (Days 8-21). From Day 22, participants received AVP-786-28 mg orally BID for the remaining 3 weeks. Participants who completed Stage 1 were eligible to participate in Stage 2.

Drug: AVP-786

Stage 2: Placebo

PLACEBO COMPARATOR

Participants who received matching placebo orally BID for 6 consecutive weeks in Stage 1 were re-randomized in Stage 2 to receive the study drug or placebo from Day 43 to Day 85.

Drug: Placebo

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)

EXPERIMENTAL

Participants who received AVP-786-18 mg in Stage 1 continued to receive AVP-786-18 mg orally BID for the 6 weeks (Days 43-85) in Stage 2..

Drug: AVP-786; Drug: Placebo

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)

EXPERIMENTAL

Participants who received AVP-786-28 mg in Stage 1 continued to receive AVP-786-28 mg orally BID for 6 weeks (Days 43-85) in Stage 2

Drug: AVP-786; Drug: Placebo

Experimental: Stage 1: Placebo to: Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mg

EXPERIMENTAL

Participants who were placebo responders or non-responders in Stage 1 received AVP-786-18 for 1 week, orally, QD, followed by AVP-786-18 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks.

Drug: AVP-786; Drug: Placebo

Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg

EXPERIMENTAL

Participants who were placebo responders or non-responders in Stage 1 received AVP-786-28 for 1 week, orally, QD, followed by AVP-786-28 BID for 2 weeks; followed by AVP-786-28 BID for the last 3 weeks.

Drug: AVP-786; Drug: Placebo

Interventions

AVP-786 DRUG

Experimental: Stage 1: Placebo to: Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mg; Stage 1: AVP-786-18 (d6-DM 18 mg/Q 4.9 mg); 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); Stage 1: AVP-786-28 (d6-DM 28 mg/Q 4.9 mg); 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); Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg

Placebo DRUG

Experimental: Stage 1: Placebo to: Stage 2: AVP-786-18 d6-DM 18 mg/Q 4.9 mg; 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); 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); Stage 1: Placebo; Stage 1: Placebo to: Stage 2: AVP-786-28 d6 DM 28 mg/Q 4.9 mg; Stage 2: Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (126)

Clinical Research Site

Phoenix, Arizona, 85032, United States

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Clinical Research Site

Scottsdale, Arizona, 85254, United States

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Clinical Research Site

Little Rock, Arkansas, 72209, United States

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Clinical Research Site#1

Irvine, California, 92697, United States

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Clinical Research Site#2

Irvine, California, 92697, United States

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Clinical Research Site

Long Beach, California, 90806, United States

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Clinical Research Site

Oceanside, California, 92056, United States

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Clinical Research Site

Orange, California, 92868, United States

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Clinical Research Site#1

San Diego, California, 92103, United States

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Clinical Research Site#2

San Diego, California, 92103, United States

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Clinical Research Site

Santa Ana, California, 92704, United States

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Clinical Research Site

Tustin, California, 92780, United States

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Denver, Colorado, 80209, United States

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Cromwell, Connecticut, 06416, United States

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New London, Connecticut, 06320, United States

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Norwalk, Connecticut, 06851, United States

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Atlantis, Florida, 33462, United States

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Clinical Research Site

Boca Raton, Florida, 33428, United States

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Clinical Research Site

Brandon, Florida, 33511, United States

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Clinical Research Site#1

Coral Gables, Florida, 33134, United States

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Clinical Research Site#2

Coral Gables, Florida, 33134, United States

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Clinical Research Site#3

Coral Gables, Florida, 33134, United States

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Clinical Research Site#1

Deerfield Beach, Florida, 33064, United States

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Clinical Research Site

Doral, Florida, 33166, United States

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Clinical Research Site

Hialeah, Florida, 33012, United States

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Clinical Research Site#1

Hialeah, Florida, 33016, United States

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Clinical Research Site#2

Hialeah, Florida, 33016, United States

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Jacksonville, Florida, 32256, United States

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Clinical Research Site

Kendall, Florida, 33175, United States

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Clinical Research Site

Kissimmee, Florida, 34741, United States

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Kissimmee, Florida, 34744, United States

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Clinical Research Site

Lake Worth, Florida, 33449, United States

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Clinical Research Site

Miami, Florida, 33122, United States

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Clinical Research Site#1

Miami, Florida, 33125, United States

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Clinical Research Site#2

Miami, Florida, 33125, United States

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Clinical Research Site

Miami, Florida, 33126, United States

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Clinical Research Site

Miami, Florida, 33133, United States

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Clinical Research Site#1

Miami, Florida, 33135, United States

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Clinical Research Site#2

Miami, Florida, 33135, United States

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Clinical Research Site

Miami, Florida, 33136, United States

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Clinical Research Site

Miami, Florida, 33137, United States

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Clinical Research Site

Miami, Florida, 33144, United States

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Clinical Research Site

Miami, Florida, 33145, United States

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Clinical Research Site

Miami, Florida, 33165, United States

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Clinical Research Site

Miami, Florida, 33175, United States

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Clinical Research Site#2

Miami, Florida, 33176, United States

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Clinical Research Site

Miami, Florida, 33183, United States

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Clinical Research Site

Miami, Florida, 33467, United States

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Clinical Research Site

Naples, Florida, 34102, United States

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Oakland Park, Florida, 33334, United States

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Clinical Research Site

Orlando, Florida, 32819, United States

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Clinical Research Site

Ormond Beach, Florida, 32174, United States

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Clinical Research Site

Palm Beach Gardens, Florida, 33410, United States

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Clinical Research Site

Palmetto Bay, Florida, 33157, United States

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Clinical Research Site#2

Pompano Beach, Florida, 33064, United States

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Sarasota, Florida, 34243, United States

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Clinical Research Site

St. Petersburg, Florida, 33713, United States

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Clinical Research Site#1

Tampa, Florida, 33609, United States

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Clinical Research Site#2

Tampa, Florida, 33609, United States

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Clinical Research Site#2

Tampa, Florida, 33613, United States

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Clinical Research Site

Tampa, Florida, 33634, United States

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The Villages, Florida, 32162, United States

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West Palm Beach, Florida, 33407, United States

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Winter Park, Florida, 32789, United States

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Atlanta, Georgia, 30342, United States

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Newnan, Georgia, 30265, United States

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Honolulu, Hawaii, 96817, United States

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Schaumburg, Illinois, 60194, United States

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Indianapolis, Indiana, 46202, United States

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Lenexa, Kansas, 66214, United States

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Paducah, Kentucky, 42003, United States

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Bedford, Massachusetts, 01730, United States

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Quincy, Massachusetts, 02169, United States

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Ann Arbor, Michigan, 48105, United States

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Paw Paw, Michigan, 49079, United States

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Hattiesburg, Mississippi, 39401, United States

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Creve Coeur, Missouri, 63141, United States

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St Louis, Missouri, 63128, United States

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Mount Arlington, New Jersey, 07856, United States

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Toms River, New Jersey, 08755, United States

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West Long Branch, New Jersey, 07764, United States

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Amherst, New York, 14226, United States

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Brooklyn, New York, 11229, United States

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New York, New York, 10032, United States

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New York, New York, 10036, United States

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Orangeburg, New York, 10962, United States

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Rochester, New York, 14620, United States

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Staten Island, New York, 10312, United States

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Durham, North Carolina, 27710, United States

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Winston-Salem, North Carolina, 27157, United States

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Akron, Ohio, 44320, United States

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Clinical Research Site

Cincinnati, Ohio, 45219, United States

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Clinical Research Site#1

Columbus, Ohio, 43210, United States

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Clinical Research Site#2

Columbus, Ohio, 43210, United States

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Dayton, Ohio, 45459, United States

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Westerville, Ohio, 43082, United States

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Edmond, Oklahoma, 73012, United States

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Oklahoma City, Oklahoma, 73103, United States

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Oklahoma City, Oklahoma, 73106, United States

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Oklahoma City, Oklahoma, 73112, United States

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Moosic, Pennsylvania, 18507, United States

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Willow Grove, Pennsylvania, 19090, United States

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East Providence, Rhode Island, 02914, United States

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Charleston, South Carolina, 29401, United States

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Clinical Research Site#2

Cordova, Tennessee, 38018, United States

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Dallas, Texas, 75231, United States

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Dallas, Texas, 75390-8898, United States

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Irving, Texas, 75062, United States

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Mansfield, Texas, 76063, United States

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Clinton, Utah, 84015, United States

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Woodstock, Vermont, 05091, United States

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Clinical Research Site#1

Tallinn, 11315, Estonia

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Clinical Research Site#2

Tallinn, 11315, Estonia

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Tartu, 50406, Estonia

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Mittweida, 9648, Germany

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Lublin, Lublin Voivodeship, 20-093, Poland

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Bydgoszcz, 85-163, Poland

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Kielce, 25-411, Poland

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Lublin, 20-064, Poland

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Poznan, 60-369, Poland

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Poznan, 61-853, Poland

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Pruszcz Gdański, 83-000, Poland

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Siemianowice Śląskie, 41-100, Poland

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Torres Vedras, 2560-280, Portugal

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Bayamón, 961, Puerto Rico

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Clinical Research Site

San Juan, 918, Puerto Rico

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MeSH Terms

Conditions

Psychomotor Agitation; Dementia; Alzheimer Disease

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Brain Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential parallel comparison design

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 13, 2015
• Study Start: July 23, 2015
• Primary Completion: January 30, 2019
• Study Completion: February 27, 2019
• Last Updated: February 13, 2023
• Results First Posted: February 13, 2023

Record last verified: 2023-01

Locations

DE (1); US (111); PL (8); ES (3); PT (1); PR (2)