Disinhibition Syndrome
Conditions
Keywords
Disinhibition
Brief summary
Treatment of disinhibition syndrome in participants with Neurodegenerative Disorder.
Detailed description
Eligible participants for this study must have a diagnosis of Neurodegenerative Disorder and must exhibit disinhibition syndrome of sufficient severity to warrant treatment. This is a multicenter, randomized, double-blind, placebo-controlled, cross-over study consisting of two 6-week treatment periods. Approximately 12 participants will be enrolled at approximately 2 centers in the United States. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study.
Interventions
DRUGAVP-786
d6-DM/Q
DRUGPlacebo
matching placebo
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of a Neurodegenerative Disorder including frontotemporal dementia, Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with Lewy bodies (DBL), vascular cognitive disorders, or Huntington's disease, at least 3 months prior to Baseline * The participant has behavior from 2 of the 3 categories of disinhibited behavior from the definition of the behavioral variant of frontotemporal dementia * The behavioral changes are not due to a pre-existing major psychiatric disorder (e.g., schizophrenia, bipolar disease, etc.) and are not due to the direct effect of systemic illness, drug action, or substance use * Disinhibition scale score of ≥4 on the 3 core disinhibition items of the Frontal Behavioral Inventory (FBI) at Screening and Baseline
Exclusion criteria
* Participants with symptoms of disinhibition that is not secondary to Neurodegenerative Disorders * Participants with myasthenia gravis * Participants with co-existent clinically significant or unstable systemic diseases that could confound the interpretation of the safety results of the study (e.g., malignancy \[except skin basal-cell carcinoma or untreated prostate cancer\], poorly controlled diabetes, poorly controlled hypertension, unstable pulmonary, renal or hepatic disease, unstable ischemic cardiac disease, dilated cardiomyopathy, or unstable valvular heart disease)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in the Disinhibition Domain of the Neuropsychiatric Inventory (NPI) | Baseline; Week 6, Week 8, and Week 14 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline for the Total NPI Score | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the NPI Total Caregiver Distress | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the NPI Disinhibition Domain Caregiver Distress | Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14 |
| Change From Baseline for the Frontal Behavioral Inventory (FBI) Total Score | Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14 |
| Change From Baseline for the FBI Disinhibition Domain Score | Baseline; Week 1, Week 3, Week 6, Week 9, Week 11, and Week 14 |
| Change From the First Assessment for the Modified Clinical Global Impression of Change (mCGIC) Scale | Week 3, Week 6, Week 11, and Week 14 |
| Change From the First Assessment for the Patient Global Impression of Change (PGIC) Scale | Week 3, Week 6, Week 11, and Week 14 |
| Change From Baseline for the Quality of Relationships (QoR) Scale | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the Quality of Life (QoL) Scale | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the Interpersonal Reactivity Index (IRI) | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the Center for Neurologic Study-Lability Scale (CNS-LS) | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the Mini-Mental State Examination (MMSE) | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the Cornell Scale for Depression in Dementia (CSDD) | Baseline; Week 6, Week 8, and Week 14 |
| Change From Baseline for the Stroop Color and Word Task | Baseline; Week 6, Week 8, and Week 14 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AVP-786; Placebo In Period 1, participants were randomized to receive AVP-786 (deuterated \[d6\]-dextromethorphan hydrobromide \[d6-DM\]/quinidine sulfate \[Q\]) once a day (OD) in the morning and placebo in the evening for the first 7 days of the study. From Day 8, participants received AVP-786 twice a day (BID) for 14 days. From Day 22, participants received a target dose of d6-DM 28 milligrams (mg)/Q 4.9 mg (AVP-786-28/4.9) BID for the remaining 3 weeks of Period 1. In Period 2, participants were randomized to receive matching placebo. The periods were separated by a 2-week washout period. | 1 |
| Placebo; AVP-786 In Period 1, participants were randomized to receive matching placebo. In Period 2, participants were randomized to receive AVP-786 OD in the morning and placebo in the evening for the first 7 days of the study. From Day 8, participants received AVP-786 BID for 14 days. From Day 22, participants received a target dose of AVP-786-28/4.9 BID for the remaining 3 weeks of Period 2. The periods were separated by a 2-week washout period. | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | AVP-786; Placebo | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | NA Participants | NA Participants |
| Race (NIH/OMB) Asian | NA Participants | NA Participants |
| Race (NIH/OMB) Black or African American | NA Participants | NA Participants |
| Race (NIH/OMB) More than one race | NA Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | NA Participants | NA Participants |
| Race (NIH/OMB) Unknown or Not Reported | NA Participants | NA Participants |
| Race (NIH/OMB) White | NA Participants | NA Participants |
| Sex: Female, Male Female | NA Participants | NA Participants |
| Sex: Female, Male Male | NA Participants | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Change From Baseline in the Disinhibition Domain of the Neuropsychiatric Inventory (NPI)
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Center for Neurologic Study-Lability Scale (CNS-LS)
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Cornell Scale for Depression in Dementia (CSDD)
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the FBI Disinhibition Domain Score
Time frame: Baseline; Week 1, Week 3, Week 6, Week 9, Week 11, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Frontal Behavioral Inventory (FBI) Total Score
Time frame: Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Interpersonal Reactivity Index (IRI)
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Mini-Mental State Examination (MMSE)
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the NPI Disinhibition Domain Caregiver Distress
Time frame: Baseline; Week 1, Week 3, Week 6, Week 8, Week 9, Week 11, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the NPI Total Caregiver Distress
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Quality of Life (QoL) Scale
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Quality of Relationships (QoR) Scale
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Stroop Color and Word Task
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From Baseline for the Total NPI Score
Time frame: Baseline; Week 6, Week 8, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From the First Assessment for the Modified Clinical Global Impression of Change (mCGIC) Scale
Time frame: Week 3, Week 6, Week 11, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Change From the First Assessment for the Patient Global Impression of Change (PGIC) Scale
Time frame: Week 3, Week 6, Week 11, and Week 14
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=1). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.