Schizophrenia
Conditions
Keywords
Negative Symptoms, Schizophrenia, AVP-786
Brief summary
The objectives of this 12-week study are to evaluate the efficacy, safety, and tolerability of AVP-786 as an adjunctive treatment compared with placebo in patients with residual schizophrenia.
Interventions
DRUGAVP-786
DRUGPlacebo
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients who meet DSM-IV-TR diagnostic criteria for schizophrenia using the M.I.N.I. version 6.0. * Patients must meet PANSS criteria * Patients currently receiving atypical antipsychotics are eligible provided they are on a stable dose
Exclusion criteria
* Patients with current major depressive disorder (MDD) * Patients with extrapyramidal syndrome secondary to their ongoing antipsychotic medication * Patients currently using anticholinergic medications * Recent in-patient hospitalization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The NSA-16 is a measure of the presence, severity, and range of negative symptoms associated with schizophrenia. It has a high interrater and test-retest reliability across languages and cultures. The NSA-16 uses a 5-factor model to describe negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation. The possible NSA-16 total score ranges from 16 to 96, with a higher score indicating a worse condition. Change was Baseline was calculated as the post-Baseline value minus the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The global level of functioning is a single score on a scale of 1 to 7 that provides the overall assessment of the participant's level of functioning, with higher scores indicative of severe impairment in functioning. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The PANSS is a 30-item clinical scale that is extensively used as a reliable and valid measure for negative symptom trials. The PANNS consists of 6 subscales: positive subscale; negative subscale; general psychopathology subscale; prosocial factors (active social avoidance, emotional withdrawal, passive/apathetic social withdrawal, stereotyped thinking, hallucinatory behavior, suspiciousness/persecution); Marder negative factors (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity and flow of conversation, motor retardation, active social avoidance); excitement component (excitement, hostility, tension, uncooperativeness, poor impulse control). Each item was scored from "1" (absent) to "7" (extremely severe). The PANSS total score ranges from 30 to 210, with a higher score indicating greater severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The negative subscale includes items N1 - N7 in the PANSS. Each item was scored from "1" (absent) to "7" (extremely severe). The score ranges from 7 to 49, with higher scores indicative of greater severity of the negative symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. |
| Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The Marder negative factors comprise 7 items of the PANSS: N1 (blunted affect); N2 (emotional withdrawal); N3 (poor rapport); N4 (passive/apathetic social withdrawal); N6 (lack of spontaneity and flow of conversation); G7 (motor retardation), and G16 (active social avoidance). Each item is scored from "1" (absent) to "7" (extremely severe). The score ranges from 7 to 49, with higher scores indicative of greater severity of the negative symptoms of schizophrenia. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The prosocial factors include items: G16 (active social avoidance); N2 (emotional withdrawal); N4 (passive/apathetic social withdrawal); N7 (stereotyped thinking); P3 (hallucinatory behavior); and P6 (suspiciousness/persecution) in the PANSS. Each item was scored from "1" (absent) to "7" (extremely severe). The score ranges from 6 to 42, with higher scores indicative of greater severity of the specific negative symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The positive subscale includes items P1 - P7 in the PANSS. Each item is scored from "1" (absent) to "7" (extremely severe). The score ranges from 7 to 49, with higher scores indicative of greater severity of the positive symptoms of schizophrenia. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The general psychopathology subscale includes items G1 - G16 in the PANSS. Each item was scored from "1" (absent) to "7" (extremely severe). The score ranges from 16 to 112, with higher scores indicative of greater severity of symptoms of schizophrenia. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The excitement component includes items: P4 (excitement); P7 (hostility); G4 (tension); G8 (uncooperativeness); and G14 (poor impulse control). Each item is scored from "1" (absent) to "7" (extremely severe). The score ranges from 5 to 35, with higher scores indicative of greater severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | NSA-16 Communication Factor Domain scores range from 4 to 24, with higher scores indicating greater clinical severity of symptoms. Negative values indicate improvement. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | NSA-16 Emotion/Affect Domain scores range from 3 to 18, with higher scores indicating a greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | NSA-16 Social Involvement Factor Domain scores range from 3 to 18, with higher scores indicating greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | NSA-16 Motivation Factor Domain scores range from 4 to 24, with higher scores indicating greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | NSA-16 Retardation Factor Domain scores range from 3 to 18, with higher scores indicating greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The MCCB is the standard tool for assessing cognitive change in trials of cognitive-enhancing agents in schizophrenia and is used to provide a relatively brief evaluation of key cognitive domains relevant to schizophrenia and related disorders. It is made up of 10 tests that measure 7 cognitive domains: Speed of Processing; Attention/Vigilance; Working Memory; Verbal Learning; Visual Learning; Reasoning and Problem Solving; and Social Cognition. The MCCB was to be conducted at approximately the same time of day (+/- 2 hours) and preferably in the morning. The MCCB composite score ranges from 0 to 70, with higher scores indicative of less severe cognition symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Mean Actual Clinical Global Impression of Severity (CGI-S) of Illness Score at Week 6 and Week 12 | Week 6 (Stage 1); Week 12 (Stage 2) | The CGI is an assessment of a participant's global functioning prior to and after initiating study medication and provides an overall clinician-determined summary measure that takes into account knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. It is based on a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering the total clinical experience, a participant is assessed on severity of mental illness at the time of rating: 1 (normal, not at all ill); 2 (borderline mentally ill); 3 (mildly ill); 4 (moderately ill); 5 (markedly ill); 6 (severely ill); or 7 (among the most extremely ill participants). Scores range from 1 to 7, with higher scores indicative of greater severity of illness. |
| Mean Actual Clinical Global Impression of Change (CGI-C) Score at Week 6 and Week 12 | Baseline, Week 6 (Stage 1), Week 12 (Stage 2) | The CGI is an assessment of the participant's global functioning prior to and after initiating a study medication and provides an overall clinician-determined summary measure that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. It is based on a 7-point scale that requires the clinician to rate the change of the participant's condition at the time of assessment, relative to the clinician's past experience with the participant's condition at admission. Considering the total clinical experienced, a participant is assessed for change of mental illness as: 1 (very much improved); 2 (much improved); 3 (minimally improved); 4 (no change); 5 (minimally worse); 6 (much worse); or 7 (very much worse). Scores range from 1 to 7, with higher scores indicative of greater severity of illness. |
| Mean Actual Patient Global Impression of Change (PGI-C) Score at Week 6 at Week 12 | Baseline, Week 6 (Stage 1), Week 12 (Stage 2) | The PGI-C is a 7-point, participant-rated scale used to assess treatment response as: 0=Not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally 6=worse; or 7=very much worse. Week 6 and Week 12 scores are relative to Stage 1 Baseline. |
| Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The CDSS is a 9-item scale derived from the Hamilton Depression Scale (Ham-D) that is designed to assess depression specifically in participants with schizophrenia. Unlike the Ham-D, the CDSS does not contain depressive symptoms that overlap with negative symptoms of schizophrenia, such as anhedonia and social withdrawal. Each item on the scale is scored as: 0 (absent); 1 (mild); 2 (moderate); or 3 (severe). The CDSS is obtained by adding each of the item scores. A score above 6 has an 82% specificity and 85% sensitivity for predicting the presence of a major depressive episode. The CDSS score ranges from 0 to 27, with higher scores indicative of severe symptoms of depression. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized task in which participants are given the opportunity on each trial to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. The test measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. The ratio of hard task choices with moderate probability reward is used as an outcome measure for negative symptoms. EEfRT scores are analyzed for 8 variables. Variable 1 is the Baseline press rate and is defined as the value coded as average presses/second. Scores range from 0 to 9, with higher scores indicative of faster button pressing ability. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 2 is the choice RT and is defined as the average RT measured in milliseconds for making a choice during the first 50 trials. Scores range from 0 to 10,000. The target range is greater than 500. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 3 is the proportion of completed task (easy or hard) during the first 50 trials. Scores range from 0 to 1, with higher scores indicative of better task compliance. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 4 is the proportion of hard task choices made for the low (12%) probability condition during the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 5 is the proportion of hard task choices made for the medium (50%) probability condition during the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 6 is the proportion of hard task choices made for the hard (88%) probability condition during the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 7 is the overall proportion of hard task choices made for the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 8 is the difference between the proportion of hard task choices made for the high probability condition during the first 50 trials of the task. Scores range from -1 to 1, with higher scores indicative of greater sensitivity to probability information. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | Treatment effect was evaluated by analyzing the proportion of participants with a 20% reduction from Baseline in the PANSS total score with SPCD analysis. |
| Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The global negative symptoms rating in the NSA-16 is a single score based on the overall impression of severity of negative symptoms on a 1 to 7 scale, where higher scores indicate greater severity. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2) | The NSA-4 is comprised of the 4 NSA-16 items as follows: 1) restricted speech quantity, 2) emotion: reduced range, 3) reduced social drive, and 4) reduced interests, as well as an overall global rating of negative symptoms. The NSA-16 is a measure of the presence, severity, and range of negative symptoms associated with schizophrenia. It has a high interrater and test-retest reliability across languages and cultures. The possible NSA-4 total score ranges from 4 to 24, with higher scores indicating greater clinical severity of symptoms. Change was Baseline was calculated as the post-Baseline value minus the Baseline value. |
Countries
United States
Participant flow
Recruitment details
Of the 145 participants randomized at the beginning of the study, 127 patients met the criteria for the Modified Intent-to-Treat (mITT) Population and were included in the Stage 1 mITT Population. A total of 108 participants were included in the Stage 2 mITT Population.
Pre-assignment details
Participant Flow data are reported for members of the mITT Population. Stage 1: participants randomized in Stage 1 who had at least 1 post-baseline NSA-16 total score assessment in Stage 1. Stage 2: participants who were re-randomized into Stage 2 and had at least 1 NSA-16 total score assessment in Stage 2 (after Week 6).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were randomized to receive placebo capsules matched to AVP-786 orally twice a day (BID) in Stage 1. | 96 |
| AVP-786 Participants were randomized to receive AVP-786 once daily (QD) on Day 1 for the first 7 days in Stage 1. Scheduled dose escalations occurred on Day 8 and Day 14 to a target dose of AVP-786-34/4.9 milligrams twice a day (d6-DM 34 mg/Q 4.9 mg BID). | 48 |
| Total | 144 |
Baseline characteristics
| Characteristic | AVP-786 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 46.5 Years STANDARD_DEVIATION 12.04 | 45.4 Years STANDARD_DEVIATION 11.23 | 44.9 Years STANDARD_DEVIATION 10.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 16 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 128 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 78 Participants | 53 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 18 Participants | 54 Participants | 36 Participants |
| Sex: Female, Male Female | 18 Participants | 45 Participants | 27 Participants |
| Sex: Female, Male Male | 30 Participants | 99 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 88 |
| other Total, other adverse events | 39 / 96 | 30 / 88 |
| serious Total, serious adverse events | 2 / 96 | 0 / 88 |
Outcome results
Primary
Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12
The NSA-16 is a measure of the presence, severity, and range of negative symptoms associated with schizophrenia. It has a high interrater and test-retest reliability across languages and cultures. The NSA-16 uses a 5-factor model to describe negative symptoms: (1) communication, (2) emotion/affect, (3) social involvement, (4) motivation, and (5) retardation. The possible NSA-16 total score ranges from 16 to 96, with a higher score indicating a worse condition. Change was Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Modified Intent-To-Treat (mITT) Population. Stage 1: randomized participants who had at least 1 post-Baseline NSA-16 total score assessment in Stage 1. Stage 2 (Stage 1 Placebo Non-responders): re-randomized participants who had at least 1 NSA-16 total score assessment in Stage 2. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 61.0 score on a scale | Standard Deviation 7.53 |
| Stage 1: AVP-786 | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -5.0 score on a scale | Standard Deviation 5.64 |
| Stage 1: Placebo | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 60.4 score on a scale | Standard Deviation 7.71 |
| Stage 1: Placebo | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -3.4 score on a scale | Standard Deviation 5.54 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 57.6 score on a scale | Standard Deviation 9.39 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -2.4 score on a scale | Standard Deviation 5.88 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -3.7 score on a scale | Standard Deviation 6.41 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the 16-Item Negative Symptom Assessment (NSA-16) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 57.6 score on a scale | Standard Deviation 9.09 |
Comparison: Sequential Parallel Comparison Design (SPCD) Weighted Ordinary Least Squares (OLS) z-statistic. Treatment differences in each stage were estimated by the Mixed Model Repeated Measures (MMRM).p-value: 0.07395% CI: [-3.75, 0.17]Mixed Models Analysis
Secondary
Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12
The NSA-4 is comprised of the 4 NSA-16 items as follows: 1) restricted speech quantity, 2) emotion: reduced range, 3) reduced social drive, and 4) reduced interests, as well as an overall global rating of negative symptoms. The NSA-16 is a measure of the presence, severity, and range of negative symptoms associated with schizophrenia. It has a high interrater and test-retest reliability across languages and cultures. The possible NSA-4 total score ranges from 4 to 24, with higher scores indicating greater clinical severity of symptoms. Change was Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.0 score on a scale | Standard Deviation 2.1 |
| Stage 1: AVP-786 | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 17.4 score on a scale | Standard Deviation 2.44 |
| Stage 1: Placebo | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.0 score on a scale | Standard Deviation 1.92 |
| Stage 1: Placebo | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 17.3 score on a scale | Standard Deviation 2.36 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.5 score on a scale | Standard Deviation 2.01 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 16.5 score on a scale | Standard Deviation 2.64 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 16.4 score on a scale | Standard Deviation 2.84 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the 4-Item NSA (NSA-4) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.5 score on a scale | Standard Deviation 1.93 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: -0.0695% CI: [-1.009, 2.911]Mixed Models Analysis
Secondary
Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12
The CDSS is a 9-item scale derived from the Hamilton Depression Scale (Ham-D) that is designed to assess depression specifically in participants with schizophrenia. Unlike the Ham-D, the CDSS does not contain depressive symptoms that overlap with negative symptoms of schizophrenia, such as anhedonia and social withdrawal. Each item on the scale is scored as: 0 (absent); 1 (mild); 2 (moderate); or 3 (severe). The CDSS is obtained by adding each of the item scores. A score above 6 has an 82% specificity and 85% sensitivity for predicting the presence of a major depressive episode. The CDSS score ranges from 0 to 27, with higher scores indicative of severe symptoms of depression. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 1.1 score on a scale | Standard Deviation 1.34 |
| Stage 1: AVP-786 | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Chane from Baseline at Week 6 | -0.2 score on a scale | Standard Deviation 1.34 |
| Stage 1: Placebo | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 0.9 score on a scale | Standard Deviation 1.31 |
| Stage 1: Placebo | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Chane from Baseline at Week 6 | -0.1 score on a scale | Standard Deviation 1.02 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 1.0 score on a scale | Standard Deviation 1.56 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 score on a scale | Standard Deviation 1.24 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 0.8 score on a scale | Standard Deviation 1.54 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.0 score on a scale | Standard Deviation 1.66 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.59595% CI: [-1.43, 2.49]Mixed Models Analysis
Secondary
Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12
The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 4 is the proportion of hard task choices made for the low (12%) probability condition during the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.021 score on a scale | Standard Deviation 0.064 |
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Stage 1 Baseline | 0.080 score on a scale | Standard Deviation 0.071 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Stage 1 Baseline | 0.0755 score on a scale | Standard Deviation 0.079 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.004 score on a scale | Standard Deviation 0.082 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Change from Baseline at Week 12 | 0.000 score on a scale | Standard Deviation 0.045 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Stage 2 Baseline | 0.040 score on a scale | Standard Deviation 0.049 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Stage 2 Baseline | 0.071 score on a scale | Standard Deviation 0.063 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for 12% Probability-Proportion High Effort Opts at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.027 score on a scale | Standard Deviation 0.051 |
p-value: 0.24695% CI: [-3.119, 0.801]ANCOVA
Secondary
Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12
The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 5 is the proportion of hard task choices made for the medium (50%) probability condition during the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.088 score on a scale | Standard Deviation 0.07 |
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.026 score on a scale | Standard Deviation 0.055 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.078 score on a scale | Standard Deviation 0.081 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.012 score on a scale | Standard Deviation 0.102 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.016 score on a scale | Standard Deviation 0.068 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.060 score on a scale | Standard Deviation 0.057 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.005 score on a scale | Standard Deviation 0.083 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for 50% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.062 score on a scale | Standard Deviation 0.078 |
p-value: 0.81895% CI: [-1.729, 2.191]ANCOVA
Secondary
Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12
The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 6 is the proportion of hard task choices made for the hard (88%) probability condition during the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.082 score on a scale | Standard Deviation 0.063 |
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.021 score on a scale | Standard Deviation 0.072 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.081 score on a scale | Standard Deviation 0.086 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.006 score on a scale | Standard Deviation 0.097 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.052 score on a scale | Standard Deviation 0.065 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.015 score on a scale | Standard Deviation 0.047 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.015 score on a scale | Standard Deviation 0.07 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for 88% Probability-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.078 score on a scale | Standard Deviation 0.074 |
p-value: 0.96895% CI: [-2, 1.92]ANCOVA
Secondary
Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12
The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 7 is the overall proportion of hard task choices made for the first 50 trials of the task. Scores range from 0 to 1, with higher scores indicative of greater effort expenditure. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.068 score on a scale | Standard Deviation 0.167 |
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.251 score on a scale | Standard Deviation 0.185 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.022 score on a scale | Standard Deviation 0.261 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.234 score on a scale | Standard Deviation 0.234 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.032 score on a scale | Standard Deviation 0.144 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.152 score on a scale | Standard Deviation 0.161 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.210 score on a scale | Standard Deviation 0.199 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for All-Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.047 score on a scale | Standard Deviation 0.176 |
p-value: 0.7695% CI: [-2.266, 1.654]ANCOVA
Secondary
Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12
The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 2 is the choice RT and is defined as the average RT measured in milliseconds for making a choice during the first 50 trials. Scores range from 0 to 10,000. The target range is greater than 500. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 1339.5 score on a scale | Standard Deviation 838.4 |
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -255.1 score on a scale | Standard Deviation 551.65 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 1659.4 score on a scale | Standard Deviation 1063.02 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -346.6 score on a scale | Standard Deviation 1108.63 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 1309.4 score on a scale | Standard Deviation 595.02 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -288.8 score on a scale | Standard Deviation 527.42 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -110.2 score on a scale | Standard Deviation 812.66 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for Choice Reaction Time (RT) 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 1283.5 score on a scale | Standard Deviation 875.79 |
p-value: 0.86295% CI: [-2.13, 1.79]ANCOVA
Secondary
Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12
The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 3 is the proportion of completed task (easy or hard) during the first 50 trials. Scores range from 0 to 1, with higher scores indicative of better task compliance. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.032 score on a scale | Standard Deviation 0.196 |
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Stage 1 Baseline | 0.790 score on a scale | Standard Deviation 0.285 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Change from Baseline at Week 6 | 0.001 score on a scale | Standard Deviation 0.209 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Stage 1 Baseline | 0.749 score on a scale | Standard Deviation 0.294 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Change from Baseline at Week 12 | 0.049 score on a scale | Standard Deviation 0.223 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Stage 2 Baseline | 0.703 score on a scale | Standard Deviation 0.329 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Stage 2 Baseline | 0.779 score on a scale | Standard Deviation 0.254 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for Completed Tasks at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.022 score on a scale | Standard Deviation 0.173 |
p-value: 0.25195% CI: [-3.109, 0.811]ANCOVA
Secondary
Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12
The EEfRT is a multi-trial computerized test that reliably measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. For each trial, participants are asked to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. EEfRT scores are analyzed for 8 variables. Variable 8 is the difference between the proportion of hard task choices made for the high probability condition during the first 50 trials of the task. Scores range from -1 to 1, with higher scores indicative of greater sensitivity to probability information. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.002 score on a scale | Standard Deviation 0.041 |
| Stage 1: AVP-786 | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.001 score on a scale | Standard Deviation 0.054 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.002 score on a scale | Standard Deviation 0.05 |
| Stage 1: Placebo | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 1 Baseline | 0.006 score on a scale | Standard Deviation 0.037 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.012 score on a scale | Standard Deviation 0.032 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.015 score on a scale | Standard Deviation 0.037 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Change from Baseline at Week 12 | 0.012 score on a scale | Standard Deviation 0.039 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the EEfRT Score for Difference - Proportion High Effort Opts 1st 50 at Week 6 and Week 12 | Stage 2 Baseline | 0.006 score on a scale | Standard Deviation 0.034 |
p-value: 0.21495% CI: [-0.717, 3.203]ANCOVA
Secondary
Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12
The EEfRT is a multi-trial computerized task in which participants are given the opportunity on each trial to choose between 2 tasks that differ in difficulty level and are associated with varying levels of monetary reward. The test measures drug effects on the willingness to expend effort in relation to the amount of reward or probability of reward. The ratio of hard task choices with moderate probability reward is used as an outcome measure for negative symptoms. EEfRT scores are analyzed for 8 variables. Variable 1 is the Baseline press rate and is defined as the value coded as average presses/second. Scores range from 0 to 9, with higher scores indicative of faster button pressing ability. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Stage 1 Baseline | 3.39 score on a scale | Standard Deviation 1.137 |
| Stage 1: AVP-786 | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Change from Baseline at Week 6 | 0.461 score on a scale | Standard Deviation 0.844 |
| Stage 1: Placebo | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Stage 1 Baseline | 3.39 score on a scale | Standard Deviation 1.112 |
| Stage 1: Placebo | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Change from Baseline at Week 6 | 0.195 score on a scale | Standard Deviation 1.181 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Stage 2 Baseline | 3.38 score on a scale | Standard Deviation 1.284 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.109 score on a scale | Standard Deviation 0.909 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Change from Baseline at Week 12 | 0.354 score on a scale | Standard Deviation 1.076 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Effort Expenditure for Reward Task (EEfRT) Score for Baseline Press Rate at Week 6 and Week 12 | Stage 2 Baseline | 3.67 score on a scale | Standard Deviation 0.904 |
p-value: 0.02295% CI: [0.324, 4.244]ANCOVA
Secondary
Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12
The MCCB is the standard tool for assessing cognitive change in trials of cognitive-enhancing agents in schizophrenia and is used to provide a relatively brief evaluation of key cognitive domains relevant to schizophrenia and related disorders. It is made up of 10 tests that measure 7 cognitive domains: Speed of Processing; Attention/Vigilance; Working Memory; Verbal Learning; Visual Learning; Reasoning and Problem Solving; and Social Cognition. The MCCB was to be conducted at approximately the same time of day (+/- 2 hours) and preferably in the morning. The MCCB composite score ranges from 0 to 70, with higher scores indicative of less severe cognition symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Stage 1 Baseline | 32.5 score on a scale | Standard Deviation 11.37 |
| Stage 1: AVP-786 | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Change from Baseline at Week 6 | 1.2 score on a scale | Standard Deviation 5.11 |
| Stage 1: Placebo | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Stage 1 Baseline | 28.8 score on a scale | Standard Deviation 13.09 |
| Stage 1: Placebo | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Change from Baseline at Week 6 | 1.6 score on a scale | Standard Deviation 4.55 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Stage 2 Baseline | 31.7 score on a scale | Standard Deviation 14.99 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -1.6 score on a scale | Standard Deviation 4.06 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Change from Baseline at Week 12 | 1.6 score on a scale | Standard Deviation 3.71 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score at Week 6 and Week 12 | Stage 2 Baseline | 28.9 score on a scale | Standard Deviation 10.69 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.07495% CI: [-0.18, 3.74]Mixed Models Analysis
Secondary
Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12
NSA-16 Communication Factor Domain scores range from 4 to 24, with higher scores indicating greater clinical severity of symptoms. Negative values indicate improvement. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.3 score on a scale | Standard Deviation 2.32 |
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 12.5 score on a scale | Standard Deviation 2.54 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 12.6 score on a scale | Standard Deviation 2.71 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.0 score on a scale | Standard Deviation 1.91 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 score on a scale | Standard Deviation 1.86 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 12.0 score on a scale | Standard Deviation 2.98 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -1.0 score on a scale | Standard Deviation 1.56 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Communication Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 11.8 score on a scale | Standard Deviation 3.12 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.06495% CI: [-3.81, 0.11]Mixed Models Analysis
Secondary
Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12
NSA-16 Emotion/Affect Domain scores range from 3 to 18, with higher scores indicating a greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 12.6 score on a scale | Standard Deviation 2.11 |
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.0 score on a scale | Standard Deviation 1.28 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.6 score on a scale | Standard Deviation 1.54 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 12.2 score on a scale | Standard Deviation 1.81 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 11.7 score on a scale | Standard Deviation 1.84 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 score on a scale | Standard Deviation 1.5 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.6 score on a scale | Standard Deviation 1.36 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Emotion/Affect Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 11.7 score on a scale | Standard Deviation 2.09 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.195% CI: [-3.6, 0.32]Mixed Models Analysis
Secondary
Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12
The global level of functioning is a single score on a scale of 1 to 7 that provides the overall assessment of the participant's level of functioning, with higher scores indicative of severe impairment in functioning. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Stage 1 Baseline | 4.7 score on a scale | Standard Deviation 0.73 |
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.4 score on a scale | Standard Deviation 0.61 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Stage 1 Baseline | 4.6 score on a scale | Standard Deviation 0.63 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.2 score on a scale | Standard Deviation 0.55 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Stage 2 Baseline | 4.5 score on a scale | Standard Deviation 0.74 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.3 score on a scale | Standard Deviation 0.52 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.3 score on a scale | Standard Deviation 0.64 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Global Level of Functioning Score at Week 6 and Week 12 | Stage 2 Baseline | 4.4 score on a scale | Standard Deviation 0.7 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.10695% CI: [-3.58, 0.34]Mixed Models Analysis
Secondary
Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12
The global negative symptoms rating in the NSA-16 is a single score based on the overall impression of severity of negative symptoms on a 1 to 7 scale, where higher scores indicate greater severity. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Stage 1 Baseline | 4.6 score on a scale | Standard Deviation 0.64 |
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.4 score on a scale | Standard Deviation 0.68 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Stage 1 Baseline | 4.6 score on a scale | Standard Deviation 0.61 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.2 score on a scale | Standard Deviation 0.64 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Stage 2 Baseline | 4.3 score on a scale | Standard Deviation 0.71 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.1 score on a scale | Standard Deviation 0.51 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.5 score on a scale | Standard Deviation 0.75 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Global Negative Symptoms Score at Week 6 and Week 12 | Stage 2 Baseline | 4.4 score on a scale | Standard Deviation 0.75 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.02695% CI: [-4.19, -0.27]Mixed Models Analysis
Secondary
Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12
NSA-16 Motivation Factor Domain scores range from 4 to 24, with higher scores indicating greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.4 score on a scale | Standard Deviation 1.96 |
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 16.5 score on a scale | Standard Deviation 2.37 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 16.7 score on a scale | Standard Deviation 2.33 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.9 score on a scale | Standard Deviation 1.8 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 score on a scale | Standard Deviation 2.13 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 15.8 score on a scale | Standard Deviation 2.61 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 15.8 score on a scale | Standard Deviation 2.39 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Motivation Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 score on a scale | Standard Deviation 2.09 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.36795% CI: [-2.86, 1.06]Mixed Models Analysis
Secondary
Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12
NSA-16 Retardation Factor Domain scores range from 3 to 18, with higher scores indicating greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Stage 1 Baseline | 7.2 score on a scale | Standard Deviation 1.54 |
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Change from Baseline at Week 6 | -0.8 score on a scale | Standard Deviation 1.46 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Stage 1 Baseline | 6.7 score on a scale | Standard Deviation 1.61 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Change from Baseline at Week 6 | -0.6 score on a scale | Standard Deviation 1.2 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Stage 2 Baseline | 6.0 score on a scale | Standard Deviation 2 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Change from Baseline at Week 12 | -0.3 score on a scale | Standard Deviation 1.2 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Change from Baseline at Week 12 | -0.5 score on a scale | Standard Deviation 1.81 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Retardation Domain Score at Week 6 at Week 12 | Stage 2 Baseline | 6.3 score on a scale | Standard Deviation 2.05 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.44795% CI: [-2.72, 1.2]Mixed Models Analysis
Secondary
Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12
NSA-16 Social Involvement Factor Domain scores range from 3 to 18, with higher scores indicating greater clinical severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 12.2 score on a scale | Standard Deviation 2.02 |
| Stage 1: AVP-786 | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.6 score on a scale | Standard Deviation 1.87 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Stage 1 Baseline | 12.2 score on a scale | Standard Deviation 2.2 |
| Stage 1: Placebo | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.3 score on a scale | Standard Deviation 1.92 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 12.1 score on a scale | Standard Deviation 2.12 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.8 score on a scale | Standard Deviation 1.4 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -1.1 score on a scale | Standard Deviation 2.51 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the NSA-16 Social Involvement Domain Score at Week 6 and Week 12 | Stage 2 Baseline | 12.0 score on a scale | Standard Deviation 2.56 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.38895% CI: [-2.82, 1.1]Mixed Models Analysis
Secondary
Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12
The excitement component includes items: P4 (excitement); P7 (hostility); G4 (tension); G8 (uncooperativeness); and G14 (poor impulse control). Each item is scored from 1 (absent) to 7 (extremely severe). The score ranges from 5 to 35, with higher scores indicative of greater severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 6.2 score on a scale | Standard Deviation 1.57 |
| Stage 1: AVP-786 | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.4 score on a scale | Standard Deviation 1.64 |
| Stage 1: Placebo | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 6.3 score on a scale | Standard Deviation 2.1 |
| Stage 1: Placebo | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.2 score on a scale | Standard Deviation 1.57 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 5.8 score on a scale | Standard Deviation 1.27 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | 0.0 score on a scale | Standard Deviation 2.04 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.1 score on a scale | Standard Deviation 1.77 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Excitement Component Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 6.7 score on a scale | Standard Deviation 2.59 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.72395% CI: [-2.31, 1.61]Mixed Models Analysis
Secondary
Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12
The general psychopathology subscale includes items G1 - G16 in the PANSS. Each item was scored from 1 (absent) to 7 (extremely severe). The score ranges from 16 to 112, with higher scores indicative of greater severity of symptoms of schizophrenia. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 29.1 score on a scale | Standard Deviation 4.66 |
| Stage 1: AVP-786 | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.7 score on a scale | Standard Deviation 4.04 |
| Stage 1: Placebo | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 30.1 score on a scale | Standard Deviation 5.05 |
| Stage 1: Placebo | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.7 score on a scale | Standard Deviation 3.21 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 29.7 score on a scale | Standard Deviation 5.4 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | 0.0 score on a scale | Standard Deviation 5.14 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -1.3 score on a scale | Standard Deviation 5.1 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS General Psychopathology Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 28.7 score on a scale | Standard Deviation 4.84 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.05495% CI: [-3.89, 0.03]Mixed Models Analysis
Secondary
Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12
The Marder negative factors comprise 7 items of the PANSS: N1 (blunted affect); N2 (emotional withdrawal); N3 (poor rapport); N4 (passive/apathetic social withdrawal); N6 (lack of spontaneity and flow of conversation); G7 (motor retardation), and G16 (active social avoidance). Each item is scored from 1 (absent) to 7 (extremely severe). The score ranges from 7 to 49, with higher scores indicative of greater severity of the negative symptoms of schizophrenia. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -2.1 score on a scale | Standard Deviation 3.34 |
| Stage 1: AVP-786 | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Stage 1 Baseline | 24.1 score on a scale | Standard Deviation 4.24 |
| Stage 1: Placebo | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Stage 1 Baseline | 24.2 score on a scale | Standard Deviation 3.81 |
| Stage 1: Placebo | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.6 score on a scale | Standard Deviation 3.48 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.8 score on a scale | Standard Deviation 2.8 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Stage 2 Baseline | 23.0 score on a scale | Standard Deviation 4.62 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Stage 2 Baseline | 22.3 score on a scale | Standard Deviation 5.45 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Marder Negative Factor Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -2.5 score on a scale | Standard Deviation 4.27 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.02495% CI: [-4.22, -0.3]Mixed Models Analysis
Secondary
Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12
The negative subscale includes items N1 - N7 in the PANSS. Each item was scored from 1 (absent) to 7 (extremely severe). The score ranges from 7 to 49, with higher scores indicative of greater severity of the negative symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -2.2 score on a scale | Standard Deviation 3.33 |
| Stage 1: AVP-786 | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 24.6 score on a scale | Standard Deviation 3.51 |
| Stage 1: Placebo | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -1.5 score on a scale | Standard Deviation 3.81 |
| Stage 1: Placebo | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 25.2 score on a scale | Standard Deviation 3.64 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -1.0 score on a scale | Standard Deviation 2.69 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 24.4 score on a scale | Standard Deviation 4.55 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 23.6 score on a scale | Standard Deviation 4.53 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Negative Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -2.3 score on a scale | Standard Deviation 3.12 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.02795% CI: [-4.16, -0.24]Mixed Models Analysis
Secondary
Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12
The positive subscale includes items P1 - P7 in the PANSS. Each item is scored from 1 (absent) to 7 (extremely severe). The score ranges from 7 to 49, with higher scores indicative of greater severity of the positive symptoms of schizophrenia. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 13.6 score on a scale | Standard Deviation 3.65 |
| Stage 1: AVP-786 | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.8 score on a scale | Standard Deviation 2.63 |
| Stage 1: Placebo | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Stage 1 Baseline | 13.4 score on a scale | Standard Deviation 2.81 |
| Stage 1: Placebo | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -0.3 score on a scale | Standard Deviation 2.57 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.4 score on a scale | Standard Deviation 1.99 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 13.1 score on a scale | Standard Deviation 3.64 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Stage 2 Baseline | 13.3 score on a scale | Standard Deviation 3.39 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Positive Subscale Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -0.3 score on a scale | Standard Deviation 2.47 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.795% CI: [-2.35, 1.57]Mixed Models Analysis
Secondary
Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12
The prosocial factors include items: G16 (active social avoidance); N2 (emotional withdrawal); N4 (passive/apathetic social withdrawal); N7 (stereotyped thinking); P3 (hallucinatory behavior); and P6 (suspiciousness/persecution) in the PANSS. Each item was scored from 1 (absent) to 7 (extremely severe). The score ranges from 6 to 42, with higher scores indicative of greater severity of the specific negative symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Stage 1 Baseline | 18.3 score on a scale | Standard Deviation 3.24 |
| Stage 1: AVP-786 | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Change from Baseline at Week 6 | -2.0 score on a scale | Standard Deviation 2.18 |
| Stage 1: Placebo | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Stage 1 Baseline | 18.4 score on a scale | Standard Deviation 2.92 |
| Stage 1: Placebo | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Change from Baseline at Week 6 | -1.1 score on a scale | Standard Deviation 2.53 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Change from Baseline at Week 12 | -0.7 score on a scale | Standard Deviation 2.02 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Stage 2 Baseline | 17.7 score on a scale | Standard Deviation 3.27 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Change from Baseline at Week 12 | -1.4 score on a scale | Standard Deviation 2.35 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the PANSS Prosocial Factor Subscale Score at Week 6 at Week 12 | Stage 2 Baseline | 17.0 score on a scale | Standard Deviation 3.3 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.00995% CI: [-4.56, -0.64]Mixed Models Analysis
Secondary
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12
The PANSS is a 30-item clinical scale that is extensively used as a reliable and valid measure for negative symptom trials. The PANNS consists of 6 subscales: positive subscale; negative subscale; general psychopathology subscale; prosocial factors (active social avoidance, emotional withdrawal, passive/apathetic social withdrawal, stereotyped thinking, hallucinatory behavior, suspiciousness/persecution); Marder negative factors (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity and flow of conversation, motor retardation, active social avoidance); excitement component (excitement, hostility, tension, uncooperativeness, poor impulse control). Each item was scored from 1 (absent) to 7 (extremely severe). The PANSS total score ranges from 30 to 210, with a higher score indicating greater severity of symptoms. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 67.4 score on a scale | Standard Deviation 8.26 |
| Stage 1: AVP-786 | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -4.7 score on a scale | Standard Deviation 6.98 |
| Stage 1: Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Stage 1 Baseline | 68.7 score on a scale | Standard Deviation 7.99 |
| Stage 1: Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Change from Baseline at Week 6 | -2.5 score on a scale | Standard Deviation 6.5 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 67.1 score on a scale | Standard Deviation 9 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -1.4 score on a scale | Standard Deviation 7.64 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Change from Baseline at Week 12 | -4.0 score on a scale | Standard Deviation 7.71 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 and Week 12 | Stage 2 Baseline | 65.6 score on a scale | Standard Deviation 8.07 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.02595% CI: [-4.21, -0.29]Mixed Models Analysis
Secondary
Mean Actual Clinical Global Impression of Change (CGI-C) Score at Week 6 and Week 12
The CGI is an assessment of the participant's global functioning prior to and after initiating a study medication and provides an overall clinician-determined summary measure that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. It is based on a 7-point scale that requires the clinician to rate the change of the participant's condition at the time of assessment, relative to the clinician's past experience with the participant's condition at admission. Considering the total clinical experienced, a participant is assessed for change of mental illness as: 1 (very much improved); 2 (much improved); 3 (minimally improved); 4 (no change); 5 (minimally worse); 6 (much worse); or 7 (very much worse). Scores range from 1 to 7, with higher scores indicative of greater severity of illness.
Time frame: Baseline, Week 6 (Stage 1), Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed. Week 6 scores are relative to Stage 1 Baseline. Week 12 scores are relative to Week 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Mean Actual Clinical Global Impression of Change (CGI-C) Score at Week 6 and Week 12 | Week 6 | 3.4 score on a scale | Standard Deviation 0.8 |
| Stage 1: Placebo | Mean Actual Clinical Global Impression of Change (CGI-C) Score at Week 6 and Week 12 | Week 6 | 3.6 score on a scale | Standard Deviation 0.69 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Mean Actual Clinical Global Impression of Change (CGI-C) Score at Week 6 and Week 12 | Week 12 | 3.8 score on a scale | Standard Deviation 0.9 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Mean Actual Clinical Global Impression of Change (CGI-C) Score at Week 6 and Week 12 | Week 12 | 3.5 score on a scale | Standard Deviation 0.8 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.056695% CI: [-3.87, 0.05]McNemar
Secondary
Mean Actual Clinical Global Impression of Severity (CGI-S) of Illness Score at Week 6 and Week 12
The CGI is an assessment of a participant's global functioning prior to and after initiating study medication and provides an overall clinician-determined summary measure that takes into account knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. It is based on a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering the total clinical experience, a participant is assessed on severity of mental illness at the time of rating: 1 (normal, not at all ill); 2 (borderline mentally ill); 3 (mildly ill); 4 (moderately ill); 5 (markedly ill); 6 (severely ill); or 7 (among the most extremely ill participants). Scores range from 1 to 7, with higher scores indicative of greater severity of illness.
Time frame: Week 6 (Stage 1); Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Mean Actual Clinical Global Impression of Severity (CGI-S) of Illness Score at Week 6 and Week 12 | Week 6 | 3.6 score on a scale | Standard Deviation 0.8 |
| Stage 1: Placebo | Mean Actual Clinical Global Impression of Severity (CGI-S) of Illness Score at Week 6 and Week 12 | Week 6 | 3.8 score on a scale | Standard Deviation 0.77 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Mean Actual Clinical Global Impression of Severity (CGI-S) of Illness Score at Week 6 and Week 12 | Week 12 | 3.7 score on a scale | Standard Deviation 0.75 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Mean Actual Clinical Global Impression of Severity (CGI-S) of Illness Score at Week 6 and Week 12 | Week 12 | 3.5 score on a scale | Standard Deviation 0.93 |
Comparison: Treatment differences in each stage were estimated by the MMRM.p-value: 0.42795% CI: [-2.75, 1.17]Mixed Models Analysis
Secondary
Mean Actual Patient Global Impression of Change (PGI-C) Score at Week 6 at Week 12
The PGI-C is a 7-point, participant-rated scale used to assess treatment response as: 0=Not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally 6=worse; or 7=very much worse. Week 6 and Week 12 scores are relative to Stage 1 Baseline.
Time frame: Baseline, Week 6 (Stage 1), Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: AVP-786 | Mean Actual Patient Global Impression of Change (PGI-C) Score at Week 6 at Week 12 | Week 6 | 3.1 score on a scale | Standard Deviation 0.94 |
| Stage 1: Placebo | Mean Actual Patient Global Impression of Change (PGI-C) Score at Week 6 at Week 12 | Week 6 | 3.2 score on a scale | Standard Deviation 1.01 |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Mean Actual Patient Global Impression of Change (PGI-C) Score at Week 6 at Week 12 | Week 12 | 3.3 score on a scale | Standard Deviation 0.78 |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Mean Actual Patient Global Impression of Change (PGI-C) Score at Week 6 at Week 12 | Week 12 | 2.9 score on a scale | Standard Deviation 1.11 |
p-value: 0.1795% CI: [-3.33, 0.59]ANCOVA
Secondary
Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12
Treatment effect was evaluated by analyzing the proportion of participants with a 20% reduction from Baseline in the PANSS total score with SPCD analysis.
Time frame: Baseline and Week 6 (Stage 1); Baseline (Week 6) and Week 12 (Stage 2)
Population: Stage 1 and Stage 2 mITT Populations
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1: AVP-786 | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 6; Response = No | 42 Participants |
| Stage 1: AVP-786 | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 6; Response = Yes | 5 Participants |
| Stage 1: Placebo | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 6; Response = No | 77 Participants |
| Stage 1: Placebo | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 6; Response = Yes | 3 Participants |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 12; Response = Yes | 1 Participants |
| Stage 1 Placebo Non-responders; Stage 2: Placebo | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 12; Response = No | 29 Participants |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 12; Response = No | 30 Participants |
| Stage 1 Placebo Non-responders; Stage 2: AVP-786 | Number of Participants With a Reduction of 20% or Greater in the PANSS Total Score at Week 6 and Week 12 | Week 12; Response = Yes | 3 Participants |
p-value: 0.071SPCD 1 degree of freedom score test