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

Otsuka

Status and phase: Completed; Phase 3

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

Treatments: Drug: AVP-786; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02442765

15-AVP-786-301

Details and patient eligibility

About

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.

Full description

Eligible participants for this study must have had a diagnosis of probable AD and must have had clinically meaningful agitation secondary to AD.

This was to be a multicenter, randomized, placebo-controlled study, consisting of 12 weeks of treatment.

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

Study medication was to be administered orally twice-daily from Day 1 through Day 85. Screening was to occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants were to be randomized into the study.

Enrollment: 387 patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

387 participants in 8 patient groups, including a placebo group

Stage 1: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

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

Experimental group

Description:

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.

Treatment:

Drug: AVP-786

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

Experimental group

Description:

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.

Treatment:

Drug: AVP-786

Stage 2: Placebo

Placebo Comparator group

Description:

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.

Treatment:

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 group

Description:

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..

Treatment:

Drug: Placebo

Drug: AVP-786

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 group

Description:

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

Treatment:

Drug: Placebo

Drug: AVP-786

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

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: AVP-786

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

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: AVP-786