Clincosm LogoSign in Get a demo

Efficacy, Safety and Tolerability Study of AVP-923 (Dextromethorphan/Quinidine) for Treatment of Symptoms of Agitation in Participants With Alzheimer's Disease

Sponsor
Avanir Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01584440
Collaborator
(none)
220
Enrollment
44
Locations
3
Arms
23.5
Actual Duration (Months)
5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objectives of the study are to evaluate the safety, tolerability and efficacy of AVP-923 compared to placebo, for the treatment of symptoms of agitation in participants with Alzheimer's Disease (AD).

Condition or Disease Intervention/Treatment Phase
Phase 2

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, double-dummy, double-blind, placebo-controlled study, consisting of 10 weeks of treatment.

Up to 200 participants will be enrolled at approximately 30-40 centers in the US.

Study medication will be administered orally twice-daily from Day 1 through Day 70. Screening must occur within 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 :
220 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Double-dummy, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of AVP-923 (Dextromethorphan/Quinidine) for the Treatment of Symptoms of Agitation in Patients With Alzheimer's Disease.
Actual Study Start Date :
Aug 13, 2012
Actual Primary Completion Date :
Jul 30, 2014
Actual Study Completion Date :
Jul 30, 2014

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Participants will receive placebo during Stage 1 and Stage 2 of the study.

Drug: Placebo
Placebo capsule
Experimental: AVP-923

Participants will receive AVP-923-20 and AVP-923-30 in a sequential manner during Stage 1 and Stage 2 of the study.

Drug: AVP-923-20
AVP-923-20: 20 mg of dextromethorphan and 10 mg of quinidine
Other Names:
  • Nuedexta

    • Drug: AVP-923-30
    AVP-923-30: 30 mg of dextromethorphan and 10 mg of quinidine
    Experimental: Placebo then AVP-923

    Participants will receive placebo in Stage 1 followed by AVP-923 in Stage 2.

    Drug: AVP-923-20
    AVP-923-20: 20 mg of dextromethorphan and 10 mg of quinidine
    Other Names:
  • Nuedexta

    • Drug: Placebo
    Placebo capsule

    Drug: AVP-923-30
    AVP-923-30: 30 mg of dextromethorphan and 10 mg of quinidine

    Outcome Measures

    Primary Outcome Measures

    1. Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain was designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (AD) and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Data are reported for only those participants contributing data to the analysis.

    Secondary Outcome Measures

    1. Number of Participants With the Indicated Type of Adverse Event [up to Week 10]

      Treatment-emergent adverse events (TEAEs) are defined as AEs that first occurred, or worsened, after the first dose of study medication and within 30 days after the permanent discontinuation of the study medication (first dose date ≤ AE start date ≤ date of last dose + 30 days)

    2. Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The total score is calculated as a sum of all 12 domain scores and thus ranges from 12 to 144. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    3. Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Sleep/nighttime behavior disorders = S/NB disorders.

    4. Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4D score is the sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    5. Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4A score is the sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    6. Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For each domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The total NPI-CDS score is calculated as the sum of all 12 domain scores and thus ranges from 0 to 60. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    7. Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the Agitation/Aggression domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    8. Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4D NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4D NPI-CDS score ranges from 0 to 20. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    9. Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4A NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4A NPI-CDS score ranges from 0 to 20. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    10. Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The CSI is a 13-question tool that is used to measure strain related to care provision and to identify families with potential caregiving concerns. There is at least one item for each of the following major domains: Employment, Financial, Physical, Social, and Time. A 0 (No) to 1 (Yes) scale is used for each of the 13 questions; thus the total score ranges from 0 to 13. Higher scores signify higher stress levels. Positive responses to 7 or more items on the index indicate a greater level of strain. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    11. Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The CSDD is a 19-item interview specifically developed to assess the signs and symptoms of major depression in participants with dementia. Each of the 19 items is rated for severity on a scale of 0 to 2 (0, absent; 1, mild or intermittent; 2, severe). The total score is calculated as the sum of the item scores and thus ranges from 0 to 38. Higher scores signify more severe depression. Scores above 10 indicate probable major depression. Scores above 18 indicate definite major depression. Scores below 6, as a rule, are associated with the absence of significant depressive symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    12. Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The MMSE is a brief test that is used to screen for cognitive impairment. The MMSE scale comprises 11 questions or simple tasks concerning orientation, memory, attention, and language to evaluate the participant's cognitive state. The anchor values are not consistent for each task. The MMSE total score is calculated by summing the item scores across all 11 tasks. A participant's total possible MMSE score ranges from 0 to 30 points. Higher scores indicate milder cognitive impairment. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    13. Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The QoL-AD is a brief, 13-item measure designed specifically to obtain a rating of the participant's quality of life (QoL) from both the participant and the caregiver. It uses simple and straightforward language and responses and includes assessments of the individual's relationships with friends and family, concerns about finances, physical condition, mood, and an overall assessment of life quality. Caregivers complete the measure as a questionnaire about the participants' QoL, whereas participants complete it in interview format about their own QoL. Each of the 13 items is rated on a 4-point scale, with 1 indicating a poor QoL and 4 indicating an excellent QoL. Total scores range from 13 to 52, with a higher score indicating a better QoL. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    14. Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70 [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The ADCS-ADL inventory measures basic activities of daily living such as dressing, conversation, eating, bathing, and grooming. The 19-item version, covering mainly basic ADL, is used to assess participants with more severe disabilities. The ADCS-ADL uses a scale from 0 to 54. Lower scores indicate declining ability. Change from Baseline is calculated as the post-Baseline value minus the Baseline value.

    15. Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57 [Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57]

      The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain was designed to collect information on the behavioral aspects of agitation/aggression in participants with probable AD and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.

    16. Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participant is asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Baseline is defined as the last non-missing assessment prior to Stage 1 randomization.

    17. Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline) [Day 36 (Stage 2 Baseline); Day 70]

      The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participant is asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization.

    18. Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) [Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70]

      The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. Baseline is defined as the last non-missing assessment prior to Stage 1 randomization.

    19. Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline) [Day 1 (Stage 1 Baseline); Day 70]

      The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization.

    20. Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use [up to Week 10]

      Concomitant medications (CMs) are defined as non-study medications with a start date on or before the final study visit, and that were either ongoing at the end of the study or had a stop date on or after the date of first dose of study drug. Drugs for the treatment of AD (e.g., donepezil, rivastigmine, galantamine, memantine) were allowed when administered at stable dose for at least 2 months prior to randomization. Concomitant use of the following medications was allowed, provided the participant had been on a stable dose for at least 1 month prior to randomization and remained stable throughout the study: medications for agitation secondary to AD; medications for nighttime management of insomnia or behavioral disturbances that included short-acting benzodiazepines, a low dose of alprazolam up to 0.5 milligrams (mg)/day, and a low dose of trazodone up to 50 mg/day; hypnotics for the treatment of insomnia; and certain classes of antidepressants.

    21. Number of Participants Using Rescue Medications [up to Week 10]

      Participants were allowed to receive oral lorazepam as rescue medication for the short-term treatment of symptoms of agitation, if deemed necessary by the investigator. Lorazepam was to be administered at doses up to 1.5 mg/day, and dosing was not to exceed 3 days in any 7-day period.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    Diagnosis of probable Alzheimer's disease (AD).

    The participant has clinically significant symptoms of agitation secondary to AD, that interfere with daily routine and for which a prescription medication is deemed indicated, in the opinion of the investigator.

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

    CGI-S score is ≥ 4 (moderately ill) at screening and baseline.

    Mini Mental State Examination (MMSE) score at screening between 8 and 28 (inclusive).

    Caregiver who is able and willing to comply with all required study procedures, ensuring that the participant attends all study visits and takes the study medication as instructed. In order to qualify as a caregiver for this study, the individual should spend time with the participant for a minimum of 4 hours on 4 separate days per week.

    Key Exclusion Criteria:

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

    Participant 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, certain cardiac conduction abnormalities including QTc prolongation, or unstable valvular heart disease).

    Participant with myasthenia gravis.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Arizona United States 85006
    2 Sun City Arizona United States 85351
    3 Fresno California United States 93720
    4 Fullerton California United States 92835
    5 Los Angeles California United States 90073
    6 Los Angeles California United States 90095
    7 San Diego California United States 92103
    8 San Francisco California United States 94109
    9 Sherman Oaks California United States 91403
    10 Temecula California United States 92591
    11 Boynton Beach Florida United States 33426
    12 Deerfield Beach Florida United States 33064
    13 Hialeah Florida United States 33012
    14 Miami Florida United States 33122
    15 Miami Florida United States 33137
    16 Miami Florida United States 33173
    17 Ocala Florida United States 34471
    18 Orlando Florida United States 32806
    19 Sunrise Florida United States 33351
    20 Tampa Florida United States 33609
    21 West Palm Beach Florida United States 33407
    22 West Palm Beach Florida United States 33409
    23 Weston Florida United States 33331
    24 Elk Grove Village Illinois United States 60007
    25 Las Vegas Nevada United States 89106
    26 Las Vegas Nevada United States 89147
    27 Summit New Jersey United States 07902
    28 Toms River New Jersey United States 08757
    29 Orangeburg New York United States 10962
    30 Rochester New York United States 14620
    31 White Plains New York United States 10605
    32 Centerville Ohio United States 45459
    33 Cincinnati Ohio United States 45227
    34 Cleveland Ohio United States 44195
    35 Columbus Ohio United States 43221
    36 Lakewood Ohio United States 44107
    37 Allentown Pennsylvania United States 18104
    38 Reading Pennsylvania United States 19604
    39 Charleston South Carolina United States 29401
    40 Houston Texas United States 77030
    41 San Antonio Texas United States 78238
    42 Salt Lake City Utah United States 84106
    43 Bennington Vermont United States 05201
    44 Spokane Washington United States 99204

    Sponsors and Collaborators

    • Avanir Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Avanir Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01584440
    Other Study ID Numbers:
    • 12-AVR-131
    First Posted:
    Apr 25, 2012
    Last Update Posted:
    Nov 26, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by Avanir Pharmaceuticals
    AVP-923-20
    AVP-923-30
    AVP-923
    Dextromethorphan
    Quinidine
    Neuropsychiatric Inventory
    Aggression
    Efficacy
    Safety
    Additional relevant MeSH terms:
    Alzheimer Disease
    Psychomotor Agitation
    Quinidine
    Dextromethorphan

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Stage 1: AVP-923 Stage 1: Placebo AVP-923 in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/Placebo in Stage 2
    Arm/Group Description Participants received oral AVP-923 during Stage 1 for 5 consecutive weeks. Participants received AVP-923-20 once daily (QD) in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 1 (Days 1 to 7), AVP-923-20 twice a day (BID) during the next 2 consecutive weeks (Days 8 to 21), and AVP-923-30 BID during the final 2 weeks of Stage 1 (Days 22 to 35). (AVP-923-20: 20 milligrams (mg) of dextromethorphan and 10 mg of quinidine; AVP-923-30: 30 mg of dextromethorphan and 10 mg of quinidine) Participants received matching oral placebo during Stage 1 for 5 consecutive weeks. Participants received oral AVP-923 during Stage 1 for 5 consecutive weeks. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 1 (Days 1 to 7), AVP-923-20 BID during the next 2 consecutive weeks (Days 8 to 21), and AVP-923-30 BID during the final 2 weeks of Stage 1 (Days 22 to 35). Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants continued to receive AVP-923-30 BID for the entire 5-week duration of Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID during the final 2 weeks of Stage 2 (Days 57 to 70). Participants received matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive AVP-923 in Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID during the final 2 weeks of Stage 2 (Days 57 to 70). Participants received matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive matching placebo BID throughout Stage 2.
    Period Title: Stage 1 (5 Weeks)
    STARTED 93 127 0 0 0
    COMPLETED 83 119 0 0 0
    NOT COMPLETED 10 8 0 0 0
    Period Title: Stage 1 (5 Weeks)
    STARTED 0 0 83 59 60
    COMPLETED 0 0 80 55 59
    NOT COMPLETED 0 0 3 4 1

    Baseline Characteristics

    Arm/Group Title AVP-923 Placebo Total
    Arm/Group Description Participants received oral AVP-923 during Stage 1 for 5 consecutive weeks. Participants received AVP-923-20 once daily (QD) in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 1 (Days 1 to 7), AVP-923-20 twice a day (BID) during the next 2 consecutive weeks (Days 8 to 21), and AVP-923-30 BID during the final 2 weeks of Stage 1 (Days 22 to 35). Participants received matching oral placebo during Stage 1 for 5 consecutive weeks. Total of all reporting groups
    Overall Participants 93 125 218
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    77.8
    (8.01)
    77.6
    (7.19)
    77.7
    (7.53)
    Sex: Female, Male (Count of Participants)
    Female
    52
    55.9%
    74
    59.2%
    126
    57.8%
    Male
    41
    44.1%
    51
    40.8%
    92
    42.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    3
    3.2%
    1
    0.8%
    4
    1.8%
    Native Hawaiian or Other Pacific Islander
    1
    1.1%
    0
    0%
    1
    0.5%
    Black or African American
    5
    5.4%
    6
    4.8%
    11
    5%
    White
    84
    90.3%
    116
    92.8%
    200
    91.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    2
    1.6%
    2
    0.9%

    Outcome Measures

    1. Primary Outcome
    Title Change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain was designed to collect information on the behavioral aspects of agitation/aggression in participants with probable Alzheimer's Disease (AD) and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Data are reported for only those participants contributing data to the analysis.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 modified Intent-to-Treat (mITT) Population: all participants randomized in Stage 1 who had at least one post-Baseline NPI agitation/aggression score in Stage 1. Stage 2 mITT Population: all placebo non-responders from Stage 1 who were re-randomized in Stage 2 and had at least one post-Week 4 NPI agitation/aggression score in Stage 2
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923.
    Measure Participants 125 93
    Day 36
    -1.7
    (3.10)
    -3.3
    (2.98)
    Day 70
    -0.8
    (3.59)
    -2.0
    (3.19)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments
    Method ANCOVA
    Comments Sequential Parallel Comparison Design (SPCD): data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter Ordinary Least Squares (OLS) Z-statistic
    Estimated Value -1.50
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.50
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.59
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    2. Secondary Outcome
    Title Number of Participants With the Indicated Type of Adverse Event
    Description Treatment-emergent adverse events (TEAEs) are defined as AEs that first occurred, or worsened, after the first dose of study medication and within 30 days after the permanent discontinuation of the study medication (first dose date ≤ AE start date ≤ date of last dose + 30 days)
    Time Frame up to Week 10

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all randomized participants who received at least one dose of study treatment
    Arm/Group Title All AVP-923 Placebo
    Arm/Group Description Participants received AVP-923 in either stage. Participants received placebo in either stage.
    Measure Participants 152 127
    Participants with ≥ 1 TEAE
    93
    100%
    55
    44%
    Participants with discontinuations due to a TEAE
    8
    8.6%
    4
    3.2%
    Participants who died
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Change in the Total NPI Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The total score is calculated as a sum of all 12 domain scores and thus ranges from 12 to 144. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Population. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -8.5
    (14.35)
    -13.5
    (17.48)
    Day 70
    -2.5
    (11.82)
    -6.0
    (2.48)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -2.46
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -4.20
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Other Statistical Analysis Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -3.78
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    4. Secondary Outcome
    Title Change in the Individual NPI Domain Scores From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score. Sleep/nighttime behavior disorders = S/NB disorders.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Population. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36, Delusions
    -0.6
    (2.93)
    -0.8
    (2.89)
    Day 36, Hallucinations
    -0.1
    (1.68)
    0.2
    (1.76)
    Day 36, Depression/dysphoria
    -1.0
    (2.89)
    -0.9
    (2.49)
    Day 36, Anxiety
    -1.2
    (3.69)
    -0.6
    (3.21)
    Day 36, Euphoria/elation
    -0.1
    (1.27)
    -0.3
    (1.85)
    Day 36, Apathy/indifference
    -0.5
    (3.69)
    -0.9
    (4.11)
    Day 36, Disinhibition
    -0.7
    (3.04)
    -0.9
    (3.46)
    Day 36, Irritability/lability
    -1.2
    (3.23)
    -2.2
    (4.08)
    Day 36, Aberrant motor behavior
    -0.4
    (3.95)
    -1.2
    (3.98)
    Day 36, S/NB disorders
    -0.1
    (2.50)
    -1.0
    (3.82)
    Day 36, Appetite/eating changes
    -1.2
    (3.25)
    -1.2
    (3.68)
    Day 70, Delusions
    -0.7
    (3.09)
    0.1
    (3.17)
    Day 70, Hallucinations
    -0.4
    (1.60)
    -0.1
    (2.03)
    Day 70, Depression/dysphoria
    0.2
    (2.36)
    0.2
    (2.20)
    Day 70, Anxiety
    -0.3
    (2.89)
    -1.0
    (2.76)
    Day 70, Euphoria/elation
    -0.0
    (1.25)
    -0.2
    (0.95)
    Day 70, Apathy/indifference
    0.4
    (1.96)
    -0.5
    (3.43)
    Day 70, Disinhibition
    -0.8
    (2.51)
    -0.8
    (2.67)
    Day 70, Irritability/lability
    -0.7
    (3.71)
    -1.0
    (3.40)
    Day 70, Aberrant motor behavior
    0.4
    (3.15)
    -0.8
    (2.52)
    Day 70, S/NB disorders
    -0.1
    (2.04)
    0.0
    (2.46)
    Day 70, Appetite/eating changes
    0.4
    (2.28)
    0.1
    (2.73)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.444
    Comments
    Method ANCOVA
    Comments Delusions Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value 0.77
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.27
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Delusions Domain; Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.78
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Delusions Domain; Day 70
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.861
    Comments
    Method ANCOVA
    Comments Hallucinations Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -0.18
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.29
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hallucinations Domain; Day 36
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.22
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hallucinations Domain; Day 70
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.749
    Comments
    Method ANCOVA
    Comments Depression/Dysphoria Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -0.32
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.07
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Depression/Dysphoria Domain; Day 36
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.10
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Depression/Dysphoria Domain; Day 70
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.416
    Comments
    Method ANCOVA
    Comments Anxiety Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -0.81
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.28
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Anxiety Domain; Day 36
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.81
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Anxiety Domain
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.287
    Comments
    Method ANCOVA
    Comments Euphoria/Elation Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -1.07
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.04
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Euphoria/Elation Domain; Day 36
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.34
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Euphoria/Elation Domain; Day 70
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.191
    Comments
    Method ANCOVA
    Comments Apathy/Indifference Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -1.31
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.16
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Apathy/Indifference Domain; Day 36
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.77
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Apathy/Indifference Domain; Day 36
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.271
    Comments
    Method ANCOVA
    Comments Disinhibition Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -1.10
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.22
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Disinhibition Domain; Day 36
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.37
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Disinhibition Domain; Day 70
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments
    Method ANCOVA
    Comments Irritability/Lability Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -2.18
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.70
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Irritability/Lability Domain; Day 36
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.93
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Irritability/Lability Domain; Day 70
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments
    Method ANCOVA
    Comments Aberrant Motor Behavior Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -2.21
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.38
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aberrant Motor Behavior Domain; Day 36
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.22
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Aberrant Motor Behavior Domain; Day 70
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.274
    Comments
    Method ANCOVA
    Comments Sleep/Nighttime Behavior Disorders Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -1.09
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 29
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.57
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sleep/Nighttime Behavior disorders Domain; Day 36
    Statistical Analysis 30
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.08
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Sleep/Nighttime Behavior disorders Domain; Day 70
    Statistical Analysis 31
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.513
    Comments
    Method ANCOVA
    Comments Appetite/Eating Changes Domain. SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -0.65
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 32
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.16
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Appetite/Eating Changes Domain; Day 36
    Statistical Analysis 33
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.24
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Appetite/Eating Changes Domain; Day 70
    5. Secondary Outcome
    Title Change in the Sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior NPI Domain (NPI4D) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4D score is the sum of the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -4.0
    (8.24)
    -7.6
    (9.08)
    Day 70
    -1.9
    (7.65)
    -4.6
    (7.31)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <=0.001
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -3.53
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -3.01
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -3.49
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    6. Secondary Outcome
    Title Change in the Sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior NPI Domain (NPI4A) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. The NPI4A score is the sum of the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domain scores, and thus ranges from 4 to 48. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -4.5
    (8.53)
    -7.3
    (9.08)
    Day 70
    -1.4
    (7.94)
    -4.8
    (7.05)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -3.34
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -2.41
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -3.94
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    7. Secondary Outcome
    Title Change in the Total Neuropsychiatric Inventory-Caregiver Distress Score (NPI-CDS) From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For each domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The total NPI-CDS score is calculated as the sum of all 12 domain scores and thus ranges from 0 to 60. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -3.6
    (6.64)
    -6.6
    (7.81)
    Day 70
    -2.0
    (5.74)
    -2.6
    (5.52)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.014
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -2.46
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -2.65
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.01
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Other Statistical Analysis Day 70
    8. Secondary Outcome
    Title Change in the NPI-CDS for the Agitation/Aggression Domain From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the Agitation/Aggression domain, the caregiver is asked to rate how emotionally distressing they find the symptom behavior on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -0.6
    (1.32)
    -1.4
    (1.54)
    Day 70
    -0.7
    (1.38)
    -0.5
    (1.44)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -2.57
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.68
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.20
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    9. Secondary Outcome
    Title Change in the NPI-CDS NPI4D Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4D NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Disinhibition, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4D NPI-CDS score ranges from 0 to 20. A higher score represents increased distress. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -1.5
    (3.39)
    -3.3
    (4.11)
    Day 70
    -1.2
    (3.08)
    -1.8
    (3.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -3.08
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.56
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.90
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    10. Secondary Outcome
    Title Change in the NPI-CDS NPI4A Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. For the NPI4A NPI-CDS score, the caregiver is asked to rate how emotionally distressing they find the symptom behavior (for the Agitation/Aggression, Irritability/Lability, Anxiety, and Aberrant Motor Behavior domains) on the following scale: 0, not at all; 1, minimally; 2, mildly; 3, moderately; 4, severely; 5, very severely or extremely. The NPI4A NPI-CDS score ranges from 0 to 20. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -1.7
    (3.34)
    -3.3
    (3.84)
    Day 70
    -1.0
    (3.51)
    -1.5
    (2.70)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -2.66
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.43
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.75
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    11. Secondary Outcome
    Title Change in the Caregiver Strain Index (CSI) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The CSI is a 13-question tool that is used to measure strain related to care provision and to identify families with potential caregiving concerns. There is at least one item for each of the following major domains: Employment, Financial, Physical, Social, and Time. A 0 (No) to 1 (Yes) scale is used for each of the 13 questions; thus the total score ranges from 0 to 13. Higher scores signify higher stress levels. Positive responses to 7 or more items on the index indicate a greater level of strain. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -0.6
    (2.06)
    -1.2
    (2.37)
    Day 70
    0.1
    (1.88)
    -0.2
    (1.62)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -1.96
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.62
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.30
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    12. Secondary Outcome
    Title Change in the Cornell Scale for Depression in Dementia (CSDD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The CSDD is a 19-item interview specifically developed to assess the signs and symptoms of major depression in participants with dementia. Each of the 19 items is rated for severity on a scale of 0 to 2 (0, absent; 1, mild or intermittent; 2, severe). The total score is calculated as the sum of the item scores and thus ranges from 0 to 38. Higher scores signify more severe depression. Scores above 10 indicate probable major depression. Scores above 18 indicate definite major depression. Scores below 6, as a rule, are associated with the absence of significant depressive symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    0.6
    (3.84)
    -1.0
    (3.43)
    Day 70
    -0.7
    (2.58)
    -0.9
    (2.93)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -2.33
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.57
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.18
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    13. Secondary Outcome
    Title Change in the Mini-Mental State Examination (MMSE) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline), as Analyzed by the Specified SPCD Methodology
    Description The MMSE is a brief test that is used to screen for cognitive impairment. The MMSE scale comprises 11 questions or simple tasks concerning orientation, memory, attention, and language to evaluate the participant's cognitive state. The anchor values are not consistent for each task. The MMSE total score is calculated by summing the item scores across all 11 tasks. A participant's total possible MMSE score ranges from 0 to 30 points. Higher scores indicate milder cognitive impairment. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -0.3
    (2.77)
    0.2
    (3.02)
    Day 70
    -0.5
    (2.53)
    0.3
    (2.76)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value 1.94
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.52
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.84
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    14. Secondary Outcome
    Title Change in the Quality of Life-Alzheimer's Disease (QoL-AD) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The QoL-AD is a brief, 13-item measure designed specifically to obtain a rating of the participant's quality of life (QoL) from both the participant and the caregiver. It uses simple and straightforward language and responses and includes assessments of the individual's relationships with friends and family, concerns about finances, physical condition, mood, and an overall assessment of life quality. Caregivers complete the measure as a questionnaire about the participants' QoL, whereas participants complete it in interview format about their own QoL. Each of the 13 items is rated on a 4-point scale, with 1 indicating a poor QoL and 4 indicating an excellent QoL. Total scores range from 13 to 52, with a higher score indicating a better QoL. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36, Cargiver
    0.3
    (4.66)
    0.4
    (4.28)
    Day 70, Caregiver
    0.9
    (4.27)
    -0.3
    (3.93)
    Day 36, Participant
    -0.0
    (5.18)
    1.3
    (6.12)
    Day 70, Participant
    0.7
    (4.26)
    1.5
    (5.06)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.469
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -0.72
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Caregiver
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.28
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Caregiver: Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.06
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Caregiver: Day 70
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.159
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value 1.41
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Participant
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 1.09
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Participant: Day 36
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.70
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Participant: Day 70
    15. Secondary Outcome
    Title Change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) Score From Day 1 (Stage 1 Baseline) to Day 36 (Stage 2 Baseline) and From Day 36 to Day 70
    Description The ADCS-ADL inventory measures basic activities of daily living such as dressing, conversation, eating, bathing, and grooming. The 19-item version, covering mainly basic ADL, is used to assess participants with more severe disabilities. The ADCS-ADL uses a scale from 0 to 54. Lower scores indicate declining ability. Change from Baseline is calculated as the post-Baseline value minus the Baseline value.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 125 93
    Day 36
    -0.8
    (3.89)
    -0.9
    (4.27)
    Day 70
    -0.6
    (3.45)
    -2.0
    (4.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.163
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -1.40
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.07
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.39
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    16. Secondary Outcome
    Title Change in the NPI Agitation/Aggression Domain Score From Day 1 (Stage 1 Baseline) to Day 8 and Day 22 and From Day 36 (Stage 2 Baseline) to Day 43 and Day 57
    Description The NPI is a retrospective interview covering 12 neuropsychiatric symptom domains and is used to evaluate psychopathology, neuropsychiatric manifestations, and caregiver distress. The Agitation/Aggression domain was designed to collect information on the behavioral aspects of agitation/aggression in participants with probable AD and clinically meaningful agitation secondary to AD. Each NPI domain is rated by the caregiver for symptom frequency and severity. Symptom frequency is rated as: 1, occasionally; 2, often; 3, frequently; 4, very frequently. Symptom severity is rated as: 1, mild; 2, moderate; 3, marked. The total domain score is calculated as the frequency score multiplied by the severity score and thus ranges from 1 to 12. A higher score represents worsening symptoms. Change from Baseline is calculated as the post-Baseline score minus the Baseline score.
    Time Frame Day 1 (Stage 1 Baseline); Days 8 and 22; Day 36 (Stage 2 Baseline); Days 43 and 57

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 124 93
    Day 8
    -1.4
    (2.73)
    -2.2
    (2.93)
    Day 22
    -1.6
    (2.86)
    -2.7
    (3.18)
    Day 43
    -1.3
    (2.92)
    -0.5
    (2.31)
    Day 57
    -1.3
    (2.86)
    -1.2
    (3.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.279
    Comments
    Method ANCOVA
    Comments SPCD: data from the Stages 1 and 2 are analyzed together using the mITT Population
    Method of Estimation Estimation Parameter OLS Z-statistic
    Estimated Value -1.08
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.76
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 8
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -1.02
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 22
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value 0.74
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 43
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter ANCOVA Least Squares Mean Difference
    Estimated Value -0.05
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 57
    17. Secondary Outcome
    Title Number of Participants With the Indicated Response on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Rating (mADCS-CGIC) Scale Agitation Domain at Day 36 and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
    Description The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participant is asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Baseline is defined as the last non-missing assessment prior to Stage 1 randomization.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 123 88
    Day 36, Marked improvement
    1
    1.1%
    8
    6.4%
    Day 36, Moderate improvement
    13
    14%
    22
    17.6%
    Day 36, Minimal improvement
    43
    46.2%
    28
    22.4%
    Day 36, No change
    48
    51.6%
    22
    17.6%
    Day 36, Minimal worsening
    12
    12.9%
    7
    5.6%
    Day 36, Moderate worsening
    6
    6.5%
    1
    0.8%
    Day 36, Marked worsening
    0
    0%
    0
    0%
    Day 70, Marked improvement
    4
    4.3%
    4
    3.2%
    Day 70, Moderate improvement
    5
    5.4%
    10
    8%
    Day 70, Minimal improvement
    11
    11.8%
    10
    8%
    Day 70, No change
    14
    15.1%
    12
    9.6%
    Day 70, Marked worsening
    9
    9.7%
    3
    2.4%
    Day 70, Moderate worsening
    0
    0%
    3
    2.4%
    Day 70, Minimal worsening
    1
    1.1%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.70
    Confidence Interval (2-Sided) 95%
    1.62 to 4.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2184
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.61
    Confidence Interval (2-Sided) 95%
    0.75 to 3.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    18. Secondary Outcome
    Title Number of Participants With the Indicated Response on the mADCS-CGIC Scale Agitation Domain at Day 70 Compared to Their Response at Day 36 (Stage 2 Baseline)
    Description The intent of the ADCS version of the CGIC is to provide a means to reliably assess the global impression of change from Baseline in a clinical trial. The mADCS-CGIC is a modification of the ADCS-CGIC instrument that focuses specifically on agitation. The participant is asked to rate their impression of change from Baseline as: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization.
    Time Frame Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 2 mITT Population. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 42 42
    Marked improvement
    4
    4.3%
    0
    0%
    Moderate improvement
    2
    2.2%
    11
    8.8%
    Minimal improvement
    8
    8.6%
    15
    12%
    No change
    19
    20.4%
    11
    8.8%
    Marked worsening
    6
    6.5%
    4
    3.2%
    Moderate worsening
    2
    2.2%
    1
    0.8%
    Minimal worsening
    1
    1.1%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0266
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.45
    Confidence Interval (2-Sided) 95%
    1.11 to 5.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    19. Secondary Outcome
    Title Number of Participants With the Indicated Categorical Response on the Patient Global Impression of Change (PGI-C) for the Caregiver Domain at Day 36 (Stage 2 Baseline) and Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
    Description The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. Baseline is defined as the last non-missing assessment prior to Stage 1 randomization.
    Time Frame Day 1 (Stage 1 Baseline); Day 36 (Stage 2 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Stage 1 and Stage 2 mITT Populations. Data are reported for only those participants contributing data to the analysis.
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 123 88
    Day 36, Very much improved
    2
    2.2%
    10
    8%
    Day 36, Much improved
    23
    24.7%
    24
    19.2%
    Day 36, Minimally improved
    30
    32.3%
    20
    16%
    Day 36, No change
    40
    43%
    20
    16%
    Day 36, Minimally worse
    23
    24.7%
    13
    10.4%
    Day 36, Much worse
    4
    4.3%
    1
    0.8%
    Day 36, Very much worse
    1
    1.1%
    0
    0%
    Day 70, Very much improved
    3
    3.2%
    3
    2.4%
    Day 70, Much improved
    4
    4.3%
    10
    8%
    Day 70, Minimally improved
    11
    11.8%
    14
    11.2%
    Day 70, No change
    13
    14%
    10
    8%
    Day 70, Minimally worse
    9
    9.7%
    4
    3.2%
    Day 70, Much worse
    4
    4.3%
    2
    1.6%
    Day 70, Very much worse
    0
    0%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.16
    Confidence Interval (2-Sided) 95%
    1.31 to 3.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 36
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.031
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.32
    Confidence Interval (2-Sided) 95%
    1.08 to 5.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments Day 70
    20. Secondary Outcome
    Title Number of Participants With the Indicated Categorical Response on the PGI-C for the Caregiver Domain at Day 70 Compared to Their Response at Day 1 (Stage 1 Baseline)
    Description The PGI-C uses a 7-point scale to assess treatment response and to rate the global impression of clinical change in a participant's agitation. The participant is asked to rate their impression of change from Baseline as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse. For placebo non-responders re-randomized to AVP-923 or placebo at Stage 2, Baseline is defined as the last non-missing assessment prior to Stage 2 re-randomization.
    Time Frame Day 1 (Stage 1 Baseline); Day 70

    Outcome Measure Data

    Analysis Population Description
    Only AVP-923/only placebo ITT Subset
    Arm/Group Title Placebo AVP-923
    Arm/Group Description All participants randomized to receive placebo in Stage 1, and all placebo non-responders re-randomized at Stage 2 to placebo All participants randomized to receive AVP-923 in Stage 1, and all placebo non-responders re-randomized at Stage 2 to AVP-923
    Measure Participants 59 81
    Very much improved
    5
    5.4%
    9
    7.2%
    Much improved
    9
    9.7%
    26
    20.8%
    Minimally improved
    17
    18.3%
    25
    20%
    No change
    14
    15.1%
    13
    10.4%
    Minimally worse
    10
    10.8%
    5
    4%
    Much worse
    4
    4.3%
    3
    2.4%
    Very much worse
    0
    0%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, AVP-923
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0048
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.41
    Confidence Interval (2-Sided) 95%
    1.31 to 4.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Secondary Outcome
    Title Number of Participants With the Indicated Change in the Concomitant Use of Allowed Psychotropic Drugs Compared to Their Baseline Use
    Description Concomitant medications (CMs) are defined as non-study medications with a start date on or before the final study visit, and that were either ongoing at the end of the study or had a stop date on or after the date of first dose of study drug. Drugs for the treatment of AD (e.g., donepezil, rivastigmine, galantamine, memantine) were allowed when administered at stable dose for at least 2 months prior to randomization. Concomitant use of the following medications was allowed, provided the participant had been on a stable dose for at least 1 month prior to randomization and remained stable throughout the study: medications for agitation secondary to AD; medications for nighttime management of insomnia or behavioral disturbances that included short-acting benzodiazepines, a low dose of alprazolam up to 0.5 milligrams (mg)/day, and a low dose of trazodone up to 50 mg/day; hypnotics for the treatment of insomnia; and certain classes of antidepressants.
    Time Frame up to Week 10

    Outcome Measure Data

    Analysis Population Description
    mITT Population: all participants randomized in Stage 1 who had at least one post-Baseline NPI Agitation/Aggression score in Stage 1, and all placebo non-responders from Stage 1 who are re-randomized in Stage 2 and had at least one post-Week 4 NPI Agitation/Aggression score in Stage 2. Only those participants who took CMs were analyzed.
    Arm/Group Title AVP-923 in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/Placebo in Stage 2
    Arm/Group Description Participants received oral AVP-923 during Stage 1 for 5 consecutive weeks. Participants received AVP-923-20 once daily (QD) in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 1 (Days 1 to 7), AVP-923-20 twice a day (BID) during the next 2 consecutive weeks (Days 8 to 21), and AVP-923-30 BID the final 2 weeks of Stage 1 (Days 22 to 35). Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants continued to receive AVP-923-30 BID for the entire 5-week duration of Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID the final 2 weeks of Stage 2 (Days 57 to 70). Participants receive matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive AVP-923 in Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID the final 2 weeks of Stage 2 (Days 57 to 70). Participants receive matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive matching placebo BID throughout Stage 2.
    Measure Participants 84 53 58
    Any change
    9
    9.7%
    8
    6.4%
    13
    6%
    Dose reduced
    1
    1.1%
    0
    0%
    1
    0.5%
    Dose increased
    0
    0%
    1
    0.8%
    1
    0.5%
    Change in frequency
    1
    1.1%
    1
    0.8%
    1
    0.5%
    Use discontinued
    2
    2.2%
    2
    1.6%
    2
    0.9%
    New usage
    7
    7.5%
    6
    4.8%
    11
    5%
    22. Secondary Outcome
    Title Number of Participants Using Rescue Medications
    Description Participants were allowed to receive oral lorazepam as rescue medication for the short-term treatment of symptoms of agitation, if deemed necessary by the investigator. Lorazepam was to be administered at doses up to 1.5 mg/day, and dosing was not to exceed 3 days in any 7-day period.
    Time Frame up to Week 10

    Outcome Measure Data

    Analysis Population Description
    mITT Population
    Arm/Group Title AVP-923 in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/Placebo in Stage 2
    Arm/Group Description Participants received oral AVP-923 during Stage 1 for 5 consecutive weeks. Participants received AVP-923-20 once daily (QD) in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 1 (Days 1 to 7), AVP-923-20 twice a day (BID) during the next 2 consecutive weeks (Days 8 to 21), and AVP-923-30 BID the final 2 weeks of Stage 1 (Days 22 to 35). Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants continued to receive AVP-923-30 BID for the entire 5-week duration of Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID the final 2 weeks of Stage 2 (Days 57 to 70). Participants receive matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive AVP-923 in Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID the final 2 weeks of Stage 2 (Days 57 to 70). Participants receive matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive matching placebo BID throughout Stage 2.
    Measure Participants 93 59 66
    Overall
    5
    5.4%
    11
    8.8%
    7
    3.2%
    Day 8 (Visit 2)
    0
    0%
    3
    2.4%
    1
    0.5%
    Day 22 (Visit 3)
    3
    3.2%
    3
    2.4%
    3
    1.4%
    Day 36 (Visit 4)
    5
    5.4%
    3
    2.4%
    3
    1.4%
    Day 43 (Visit 5)
    2
    2.2%
    3
    2.4%
    5
    2.3%
    Day 57 (Visit 6)
    1
    1.1%
    3
    2.4%
    4
    1.8%
    Day 70 (Visit 70)
    2
    2.2%
    3
    2.4%
    3
    1.4%

    Adverse Events

    Time Frame up to Week 10
    Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs), defined as AEs that first occurred, or worsened, after the first dose of study medication and within 30 days after the permanent discontinuation of the study medication (first dose date ≤ AE start date ≤ date of last dose + 30 days), are reported. TEAEs were collected in members of the Safety Population, comprised of all randomized participants who received at least one dose of study treatment.
    Arm/Group Title AVP-923 in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/Placebo in Stage 2
    Arm/Group Description Participants received oral AVP-923 during Stage 1 for 5 consecutive weeks. Participants received AVP-923-20 once daily (QD) in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 1 (Days 1 to 7), AVP-923-20 twice a day (BID) during the next 2 consecutive weeks (Days 8 to 21), and AVP-923-30 BID during the final 2 weeks of Stage 1 (Days 22 to 35). Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants continued to receive AVP-923-30 BID for the entire 5-week duration of Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID during the final 2 weeks of Stage 2 (Days 57 to 70). Participants received matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive AVP-923 in Stage 2. Participants received AVP-923-20 QD in the morning and placebo in the evening (to maintain the blind) during the first week of Stage 2 (Days 36 to 42), AVP-923-20 BID during the next 2 consecutive weeks (Days 43 to 56), and AVP-923-30 BID during the final 2 weeks of Stage 2 (Days 57 to 70). Participants received matching oral placebo during Stage 1 for 5 consecutive weeks. Participants who completed Stage 1 were eligible to participate in Stage 2 of the study. Participants who were randomized to placebo in Stage 1 were stratified (based on their clinical response during Stage 1) into two subgroups (responders or non-responders) and were re-randomized to receive matching placebo BID throughout Stage 2.
    All Cause Mortality
    AVP-923 in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/Placebo in Stage 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/93 (0%) 0/59 (0%) 0/68 (0%)
    Serious Adverse Events
    AVP-923 in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/Placebo in Stage 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/93 (9.7%) 3/59 (5.1%) 6/68 (8.8%)
    Blood and lymphatic system disorders
    Anaemia 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Idiopathic Thrombocytopenic Purpura 0/93 (0%) 0/59 (0%) 1/68 (1.5%)
    Cardiac disorders
    Acute Myocardial Infarction 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Bradycardia 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Ear and labyrinth disorders
    Vertigo 0/93 (0%) 0/59 (0%) 1/68 (1.5%)
    General disorders
    Chest Pain 2/93 (2.2%) 0/59 (0%) 0/68 (0%)
    Infections and infestations
    Kidney Infection 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Pneumonia 0/93 (0%) 1/59 (1.7%) 1/68 (1.5%)
    Gastroenteritis 0/93 (0%) 0/59 (0%) 1/68 (1.5%)
    Injury, poisoning and procedural complications
    Femur Fracture 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Contusion 0/93 (0%) 0/59 (0%) 1/68 (1.5%)
    Metabolism and nutrition disorders
    Dehydration 0/93 (0%) 1/59 (1.7%) 0/68 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon Cancer 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Nervous system disorders
    Cerebrovascular Accident 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Transient Ischaemic Attack 0/93 (0%) 0/59 (0%) 1/68 (1.5%)
    Psychiatric disorders
    Aggression 0/93 (0%) 1/59 (1.7%) 0/68 (0%)
    Agitation 0/93 (0%) 1/59 (1.7%) 1/68 (1.5%)
    Renal and urinary disorders
    Haematuria 1/93 (1.1%) 0/59 (0%) 0/68 (0%)
    Other (Not Including Serious) Adverse Events
    AVP-923 in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/AVP-923 in Stage 2 Placebo in Stage 1/Placebo in Stage 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/93 (25.8%) 12/59 (20.3%) 17/68 (25%)
    Gastrointestinal disorders
    Diarrhoea 5/93 (5.4%) 4/59 (6.8%) 4/68 (5.9%)
    Infections and infestations
    Urinary Tract Infection 5/93 (5.4%) 3/59 (5.1%) 4/68 (5.9%)
    Injury, poisoning and procedural complications
    Fall 10/93 (10.8%) 3/59 (5.1%) 4/68 (5.9%)
    Musculoskeletal and connective tissue disorders
    Back Pain 0/93 (0%) 3/59 (5.1%) 1/68 (1.5%)
    Nervous system disorders
    Dizziness 6/93 (6.5%) 1/59 (1.7%) 2/68 (2.9%)
    Psychiatric disorders
    Agitation 3/93 (3.2%) 1/59 (1.7%) 5/68 (7.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Avanir Medical Information
    Organization Avanir Pharmaceuticals, Inc.
    Phone 855-572-2722
    Email medinfo@avanir.com
    Responsible Party:
    Avanir Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01584440
    Other Study ID Numbers:
    • 12-AVR-131
    First Posted:
    Apr 25, 2012
    Last Update Posted:
    Nov 26, 2021
    Last Verified:
    Oct 1, 2021