Schizophrenia
Conditions
Brief summary
This multicenter study assessed the effects of 24 weeks of basmisanil treatment on cognition and functioning of stable schizophrenia participants treated with antipsychotics.
Interventions
DRUGBasmisanil
Participants received either 80 milligrams (mg) or 240 mg of Basmisanil, as per the dosing schedules described above.
DRUGPlacebo
Participants received matching Placebo to Basmisanil, as per the dosing schedules described above.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of schizophrenia of any type utilizing the Mini International Neuropsychiatric Interview and diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) direct clinical assessments, family informants and past medical records * Evidence of stability of symptoms for 3 months at screening, that is, without hospitalizations for schizophrenia or increase in level of psychiatric care due to worsening of symptoms of schizophrenia * Participants with schizophrenia clinical symptom severity defined by the following: hallucinatory behavior item score less than or equal to (\</=) 5 and a delusion item score \</= 5 of the PANSS * Participants on a stable regimen of antipsychotic therapy for at least 3 months at screening and receiving no more than two antipsychotics
Exclusion criteria
* Participants with current DSM-5 diagnosis other than schizophrenia including bipolar disorder, schizoaffective disorder and major depressive disorder * Clinically significant neurological illness or significant head trauma that affects cognitive function, in the judgment of the principal investigator * Full scale intelligence quotient \</=65 on the Wechsler Abbreviated Scale of Intelligence at screening * Positive result at screening for hepatitis B, hepatitis C, or human immunodeficiency virus-1 and 2 * Moderate to severe substance use disorder (other than nicotine or caffeine), as defined by the DSM-5, within the last 12 months * Suicide attempt within 1 year or currently at risk of suicide in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score | Baseline up to Week 24 | The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB neurocognitive composite T-score is a standardized mean of the six domain scores (excluding social cognition). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher composite T-score represents lower impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Baseline up to Week 24 | The SQLS is a patient reported scale consisting of 33 items: 2 domain scores (Cognition & Vitality Score \[SQLS-CV\] and Psycho-social Score \[SQLS-P\]) as well as a Total score (SQLS-T) are derived. The overall score range is from 0 to 100. On all scales, higher scores represent a lower quality of life. |
| Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Baseline up to Week 24 | The Paired Associates Learning (PAL I and II) of the WMS-IV (Wechsler Memory Scale Fourth edition) is a test of verbal learning and memory that requires the participant to learn novel word pairs. The participant learns the word pairs across learning trials and is asked to recall them immediately (PAL I) or after a 30-minute delay (PAL II). Data is presented here for 3 Scores: VPA I total raw score, VPA II total raw score and VPA II Recognition total raw score. The total raw score ranges for these 3 Scores are 0 to 56, 0 to 14 and 0 to 40 respectively, with larger total raw scores indicating better performance. |
| Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Baseline up to Week 24 | Logical memory (LM) assesses narrative memory under free-recall conditions. Two short stories are presented orally. The examinee is asked to retell each story from memory immediately after hearing it (LM I). In the delayed condition (LM II), the examinee is asked to retell both stories from the immediate condition (delayed free recall). Data is presented here for 2 Scores: LM I total raw score and LM II total raw score. The total raw score range is from 0 to 50 with larger total raw scores indicating better performance. |
| Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores | Baseline up to Week 24 | The TMT consists of two parts: Trail Making Part A, which is a part of the standard MCCB and Trail Making Part B additionally included in this study. Circles containing numbers (Part A) or both numbers and letters (Part B) must be sequentially connected. The difference (ratio) in performance between Part A and Part B reflects executive processes and will be used to assess executive functioning including cognitive set shifting abilities and data for this ratio is presented here. Smaller ratio values, hence decreases from baseline (TMT-B/TMT-A ratio values below 1) indicate higher executive functioning capabilities. |
| Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score | Baseline up to Week 24 | The PSP Total Score is an integer result in the range of 0 to 100. Larger values, hence increases from baseline in the PSP total score, indicate higher social and personal functioning. |
| Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score | Baseline up to Week 24 | The main parameter of interest for the Schizophrenia Cognition Rating Scale (SCoRS) is the SCoRS 'Total Score'. The total score range is from 0 to 80 with lower scores indicating better day-to-day functioning. |
| Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline up to Week 24 | The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher T-score represents lower impairment. |
| Change From Baseline to Week 24 in Clinical Global Impression Improvement (CGI-I) Rating | Baseline up to Week 24 | Values for the CGI-I Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment. |
| Percentage of Participants With Adverse Events (AEs) | Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks) | An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events. |
| Apparent Clearance of Basmisanil at Steady State (CL/F,ss) | Pre-dose (hour 0) in Days 7, 14, 42, 84, 168 | Population PK model estimated apparent oral clearance of Basmisanil at steady-state. |
| Apparent Volume of Distribution of Basmisanil at Steady State (Vz/F,ss) | Pre-dose (hour 0) in Days 7, 14, 42, 84, 168 | Population PK model estimated apparent volume of distribution of Basmisanil at steady-state. |
| Area Under the Curve of Basmisanil at Steady State (AUC,ss) | Pre-dose (hour 0) in Days 7, 14, 42, 84, 168 | Population PK model estimated AUC of Basmisanil at steady-state. |
| Maximum Plasma Concentration of Basmisanil at Steady State (Cmax,ss) | Pre-dose (hour 0) in Days 7, 14, 42, 84, 168 | Population PK model estimated maximum plasma concentration of Basmisanil at steady-state (ss). |
| Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating | Baseline up to Week 24 | Values for the CGI-S Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 37 centers in 1 country.
Pre-assignment details
Overall, 214 participants were enrolled into the study across 37 sites in the US. Of these, 213 participants received study treatment and were included in the Intent-To-Treat (ITT) and Safety populations. One participant randomized to the placebo arm withdrew prior to the first study treatment administration.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks. | 81 |
| Basmisanil 80mg BID Participants received Basmisanil 80 mg orally twice daily (BID) for 24 weeks. | 54 |
| Basmisanil 240mg BID Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks. | 78 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
| Overall Study | Completed or Discontinued information is missing | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 8 | 4 | 3 |
| Overall Study | Multiple Reasons | 1 | 0 | 1 |
| Overall Study | Non-Compliance With Study Drug | 0 | 2 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 8 | 10 |
Baseline characteristics
| Characteristic | Placebo | Basmisanil 80mg BID | Basmisanil 240mg BID | Total |
|---|---|---|---|---|
| Age, Continuous | 36.4 Years STANDARD_DEVIATION 8.2 | 36.8 Years STANDARD_DEVIATION 8.6 | 37.4 Years STANDARD_DEVIATION 8.4 | 36.9 Years STANDARD_DEVIATION 8.4 |
| Race/Ethnicity, Customized Asian | 3 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 51 Participants | 30 Participants | 51 Participants | 132 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 13 Participants | 7 Participants | 12 Participants | 32 Participants |
| Race/Ethnicity, Customized MULTIPLE | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 68 Participants | 47 Participants | 66 Participants | 181 Participants |
| Race/Ethnicity, Customized UNKNOWN | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 23 Participants | 23 Participants | 71 Participants |
| Sex: Female, Male Female | 20 Participants | 12 Participants | 18 Participants | 50 Participants |
| Sex: Female, Male Male | 61 Participants | 42 Participants | 60 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 54 | 0 / 78 |
| other Total, other adverse events | 10 / 81 | 10 / 54 | 12 / 78 |
| serious Total, serious adverse events | 5 / 81 | 0 / 54 | 4 / 78 |
Outcome results
Primary
Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score
The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). The MCCB neurocognitive composite T-score is a standardized mean of the six domain scores (excluding social cognition). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher composite T-score represents lower impairment.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score | Baseline | 32.50 Composite T-Score | Standard Deviation 14.47 |
| Placebo | Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score | Week 12 Day 84 | -0.17 Composite T-Score | Standard Deviation 5.07 |
| Placebo | Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score | Week 24 Day 168 | 1.08 Composite T-Score | Standard Deviation 5.78 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score | Baseline | 32.36 Composite T-Score | Standard Deviation 11.44 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score | Week 12 Day 84 | -0.28 Composite T-Score | Standard Deviation 6.08 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MATRICS Consensus Cognitive Battery (MCCB) Neurocognitive Composite Score | Week 24 Day 168 | 1.36 Composite T-Score | Standard Deviation 4.8 |
Comparison: Week 12 Day 84p-value: 0.7390% CI: [-2.11, 1.38]Mixed Models Analysis
Comparison: Week 24 Day 168p-value: 0.79390% CI: [-1.47, 2.02]Mixed Models Analysis
Secondary
Apparent Clearance of Basmisanil at Steady State (CL/F,ss)
Population PK model estimated apparent oral clearance of Basmisanil at steady-state.
Time frame: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168
Population: Please note that for this Outcome Measure, incomplete PK data was collected as a result of early termination of the study which meant that data for the (CL/F,ss) parameter could not be generated via the Population PK model.
Secondary
Apparent Volume of Distribution of Basmisanil at Steady State (Vz/F,ss)
Population PK model estimated apparent volume of distribution of Basmisanil at steady-state.
Time frame: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168
Population: Please note that for this Outcome Measure, incomplete PK data was collected as a result of early termination of the study which meant that data for the (Vz/F,ss) parameter could not be generated via the Population PK model.
Secondary
Area Under the Curve of Basmisanil at Steady State (AUC,ss)
Population PK model estimated AUC of Basmisanil at steady-state.
Time frame: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168
Population: The Safety-evaluable population was defined as all participants who received at least one dose of study medication, whether prematurely withdrawn from the study or not. Data are summarized according to actual treatment arm participants were randomized to. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Area Under the Curve of Basmisanil at Steady State (AUC,ss) | 41640 ng*mL/hr |
| Basmisanil 240mg BID | Area Under the Curve of Basmisanil at Steady State (AUC,ss) | 87624 ng*mL/hr |
Secondary
Change From Baseline to Week 24 in Clinical Global Impression Improvement (CGI-I) Rating
Values for the CGI-I Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Clinical Global Impression Improvement (CGI-I) Rating | Week 12 Day 84 | -0.45 Scores on a Scale | Standard Deviation 0.86 |
| Placebo | Change From Baseline to Week 24 in Clinical Global Impression Improvement (CGI-I) Rating | Week 24 Day 168 | -0.62 Scores on a Scale | Standard Deviation 1.01 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Clinical Global Impression Improvement (CGI-I) Rating | Week 12 Day 84 | -0.45 Scores on a Scale | Standard Deviation 0.86 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Clinical Global Impression Improvement (CGI-I) Rating | Week 24 Day 168 | -0.64 Scores on a Scale | Standard Deviation 0.91 |
Comparison: Week 12 Day 84p-value: 0.86590% CI: [-0.28, 0.23]Mixed Models Analysis
Comparison: Week 24 Day 168p-value: 0.96490% CI: [-0.31, 0.29]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating
Values for the CGI-S Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating | Baseline | 2.45 Scores on a Scale | Standard Deviation 0.62 |
| Placebo | Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating | Week 12 Day 84 | -0.21 Scores on a Scale | Standard Deviation 0.67 |
| Placebo | Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating | Week 24 Day 168 | -0.19 Scores on a Scale | Standard Deviation 0.56 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating | Baseline | 2.39 Scores on a Scale | Standard Deviation 0.75 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating | Week 12 Day 84 | -0.24 Scores on a Scale | Standard Deviation 0.6 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Clinical Global Impression Severity (CGI-S) Rating | Week 24 Day 168 | -0.29 Scores on a Scale | Standard Deviation 0.76 |
Comparison: Week 12 Day 84p-value: 0.83990% CI: [-0.22, 0.17]Mixed Models Analysis
Comparison: Week 24 Day 168p-value: 0.62590% CI: [-0.27, 0.15]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
The MCCB is a cognitive battery to assess 7 domains recommended by the MATRICS initiative (i.e., working memory, verbal learning, speed of processing, attention/vigilance, visual learning, social cognition, reasoning and problem solving). Raw scores are converted to age and sex adjusted t-scores which are standardized to normative data, and have a mean of 50 and standard deviation of 10 in the general healthy population. A higher T-score represents lower impairment.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Attention/Vigilance) | 40.75 T-score | Standard Deviation 12.31 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Attention/Vigilance) | -0.16 T-score | Standard Deviation 8 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Attention/Vigilance) | 0.63 T-score | Standard Deviation 6.89 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Reasoning and Problem Solving) | 42.75 T-score | Standard Deviation 12.61 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Reasoning and Problem Solving) | 0.05 T-score | Standard Deviation 8.94 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Reasoning and Problem Solving) | 1.69 T-score | Standard Deviation 7.23 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Social Cognition) | 37.79 T-score | Standard Deviation 13.3 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Social Cognition) | 0.62 T-score | Standard Deviation 7.74 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Social Cognition) | -1.71 T-score | Standard Deviation 7.24 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Speed of Processing) | 37.08 T-score | Standard Deviation 13.1 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Speed of Processing) | -1.48 T-score | Standard Deviation 7.41 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Speed of Processing) | 0.37 T-score | Standard Deviation 6.85 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Verbal Learning) | 37.34 T-score | Standard Deviation 9.2 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Verbal Learning) | 0.26 T-score | Standard Deviation 7.99 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Verbal Learning) | 0.46 T-score | Standard Deviation 8.33 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Visual Learning) | 35.96 T-score | Standard Deviation 12.18 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Visual Learning) | -0.91 T-score | Standard Deviation 8.14 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Visual Learning) | -0.98 T-score | Standard Deviation 8.56 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Working Memory) | 35.99 T-score | Standard Deviation 12.56 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Working Memory) | 1.62 T-score | Standard Deviation 6.99 |
| Placebo | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Working Memory) | 2.37 T-score | Standard Deviation 6.34 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Speed of Processing) | -1.66 T-score | Standard Deviation 6.07 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Attention/Vigilance) | 39.66 T-score | Standard Deviation 12.08 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Working Memory) | 36.23 T-score | Standard Deviation 10.09 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Attention/Vigilance) | -0.14 T-score | Standard Deviation 8.8 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Speed of Processing) | 0.13 T-score | Standard Deviation 4.88 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Attention/Vigilance) | 0.51 T-score | Standard Deviation 8.49 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Visual Learning) | -0.48 T-score | Standard Deviation 9.35 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Reasoning and Problem Solving) | 43.71 T-score | Standard Deviation 10.12 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Verbal Learning) | 36.53 T-score | Standard Deviation 7.41 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Reasoning and Problem Solving) | 0.05 T-score | Standard Deviation 6.07 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Working Memory) | 1.76 T-score | Standard Deviation 6.68 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Reasoning and Problem Solving) | 2.18 T-score | Standard Deviation 6.13 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Verbal Learning) | 0.45 T-score | Standard Deviation 7.01 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Social Cognition) | 38.38 T-score | Standard Deviation 13.09 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Visual Learning) | 0.53 T-score | Standard Deviation 9.33 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Social Cognition) | -0.62 T-score | Standard Deviation 8.55 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Verbal Learning) | 0.36 T-score | Standard Deviation 6.53 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 24 Day 168 (Social Cognition) | 0.96 T-score | Standard Deviation 7.1 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Week 12 Day 84 (Working Memory) | 0.76 T-score | Standard Deviation 6.41 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Speed of Processing) | 37.81 T-score | Standard Deviation 12.7 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in MCCB Cognitive Domain Scores | Baseline (Visual Learning) | 35.38 T-score | Standard Deviation 11.98 |
Comparison: Week 12 Day 84 (Attention/Vigilance)p-value: 0.55690% CI: [-3.46, 1.64]Mixed Models Analysis
Comparison: Week 24 Day 168 (Attention/Vigilance)p-value: 0.84890% CI: [-2.59, 2.05]Mixed Models Analysis
Comparison: Week 12 Day 84 (Reasoning and Problem Solving)p-value: 0.97390% CI: [-2.08, 2.16]Mixed Models Analysis
Comparison: Week 24 Day 168 (Reasoning and Problem Solving)p-value: 0.65190% CI: [-1.53, 2.67]Mixed Models Analysis
Comparison: Week 12 Day 84 (Social Cognition)p-value: 0.3590% CI: [-3.89, 1.08]Mixed Models Analysis
Comparison: Week 24 Day 168 (Social Cognition)p-value: 0.12190% CI: [-0.14, 4.5]Mixed Models Analysis
Comparison: Week 12 Day 84 (Speed of Processing)p-value: 0.91190% CI: [-2.1, 1.83]Mixed Models Analysis
Comparison: Week 24 Day 168 (Speed of Processing)p-value: 0.98790% CI: [-1.99, 2.03]Mixed Models Analysis
Comparison: Week 12 Day 84 (Verbal Learning)p-value: 0.80390% CI: [-2.62, 1.93]Mixed Models Analysis
Comparison: Week 24 Day 168 (Verbal Learning)p-value: 0.50290% CI: [-3.26, 1.38]Mixed Models Analysis
Comparison: Week 12 Day 84 (Visual Learning)p-value: 0.94590% CI: [-2.74, 2.52]Mixed Models Analysis
Comparison: Week 24 Day 168 (Visual Learning)p-value: 0.48890% CI: [-1.54, 3.76]Mixed Models Analysis
Comparison: Week 12 Day 84 (Working Memory)p-value: 0.26290% CI: [-3.38, 0.64]Mixed Models Analysis
Comparison: Week 24 Day 168 (Working Memory)p-value: 0.48990% CI: [-3.01, 1.23]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score
The PSP Total Score is an integer result in the range of 0 to 100. Larger values, hence increases from baseline in the PSP total score, indicate higher social and personal functioning.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score | Baseline | 59.82 Scores on a Scale | Standard Deviation 11.88 |
| Placebo | Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score | Week 12 Day 84 | 3.13 Scores on a Scale | Standard Deviation 8.3 |
| Placebo | Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score | Week 24 Day 168 | 3.75 Scores on a Scale | Standard Deviation 9.66 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score | Baseline | 60.88 Scores on a Scale | Standard Deviation 10.87 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score | Week 12 Day 84 | 2.26 Scores on a Scale | Standard Deviation 8.68 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Personal and Social Performance (PSP) Total Score | Week 24 Day 168 | 4.14 Scores on a Scale | Standard Deviation 10.05 |
Comparison: Week 12 Day 84p-value: 0.32390% CI: [-3.63, 0.91]Mixed Models Analysis
Comparison: Week 24 Day 168p-value: 0.57990% CI: [-3.77, 1.88]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores
The TMT consists of two parts: Trail Making Part A, which is a part of the standard MCCB and Trail Making Part B additionally included in this study. Circles containing numbers (Part A) or both numbers and letters (Part B) must be sequentially connected. The difference (ratio) in performance between Part A and Part B reflects executive processes and will be used to assess executive functioning including cognitive set shifting abilities and data for this ratio is presented here. Smaller ratio values, hence decreases from baseline (TMT-B/TMT-A ratio values below 1) indicate higher executive functioning capabilities.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores | Baseline | 3.27 Ratio | Standard Deviation 1.65 |
| Placebo | Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores | Week 12 Day 84 | -0.37 Ratio | Standard Deviation 1.19 |
| Placebo | Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores | Week 24 Day 168 | -0.23 Ratio | Standard Deviation 2 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores | Baseline | 3.12 Ratio | Standard Deviation 1.58 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores | Week 12 Day 84 | -0.12 Ratio | Standard Deviation 1.34 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Ratio Between Trail Making Test (TMT)- Part B and TMT- Part A Scores | Week 24 Day 168 | -0.06 Ratio | Standard Deviation 1.22 |
Comparison: Week 12 Day 84p-value: 0.52790% CI: [0.94, 1.15]Mixed Models Analysis
Comparison: Week 24 Day 168p-value: 0.63690% CI: [0.92, 1.17]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score
The main parameter of interest for the Schizophrenia Cognition Rating Scale (SCoRS) is the SCoRS 'Total Score'. The total score range is from 0 to 80 with lower scores indicating better day-to-day functioning.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score | Baseline | 37.07 Scores on a Scale | Standard Deviation 8.52 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score | Week 12 Day 84 | -2.91 Scores on a Scale | Standard Deviation 6.06 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score | Week 24 Day 168 | -3.71 Scores on a Scale | Standard Deviation 7.19 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score | Baseline | 36.53 Scores on a Scale | Standard Deviation 9.84 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score | Week 12 Day 84 | -3.66 Scores on a Scale | Standard Deviation 5.78 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Cognition Rating Scale (SCoRS) Total Score | Week 24 Day 168 | -4.02 Scores on a Scale | Standard Deviation 7.79 |
Comparison: Week 12 Day 84p-value: 0.49390% CI: [-2.27, 0.94]Mixed Models Analysis
Comparison: Week 24 Day 168p-value: 0.92690% CI: [-2.32, 2.07]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS)
The SQLS is a patient reported scale consisting of 33 items: 2 domain scores (Cognition & Vitality Score \[SQLS-CV\] and Psycho-social Score \[SQLS-P\]) as well as a Total score (SQLS-T) are derived. The overall score range is from 0 to 100. On all scales, higher scores represent a lower quality of life.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 24 Day 168 (SQLS Total Score) | -1.38 Scores on a Scale | Standard Deviation 12.89 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Baseline (SQLS Cognition & Vitality Score) | 33.81 Scores on a Scale | Standard Deviation 17.41 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 12 Day 84 (SQLS Cognition & Vitality Score) | -2.26 Scores on a Scale | Standard Deviation 12.66 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 24 Day 168 (SQLS Cognition & Vitality Score) | -0.78 Scores on a Scale | Standard Deviation 15.71 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Baseline (SQLS Psychosocial Score) | 31.48 Scores on a Scale | Standard Deviation 20.26 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 12 Day 84 (SQLS Psychosocial Score) | -0.88 Scores on a Scale | Standard Deviation 12.42 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 24 Day 168 (SQLS Psychosocial Score) | -1.78 Scores on a Scale | Standard Deviation 12.87 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Baseline (SQLS Total Score) | 32.40 Scores on a Scale | Standard Deviation 18.51 |
| Placebo | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 12 Day 84 (SQLS Total Score) | -1.42 Scores on a Scale | Standard Deviation 11.8 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Baseline (SQLS Total Score) | 32.14 Scores on a Scale | Standard Deviation 19.19 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 12 Day 84 (SQLS Psychosocial Score) | 0.80 Scores on a Scale | Standard Deviation 14.49 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Baseline (SQLS Cognition & Vitality Score) | 34.21 Scores on a Scale | Standard Deviation 18.59 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 24 Day 168 (SQLS Total Score) | -2.66 Scores on a Scale | Standard Deviation 12.31 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 12 Day 84 (SQLS Cognition & Vitality Score) | 0.21 Scores on a Scale | Standard Deviation 14 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 24 Day 168 (SQLS Psychosocial Score) | -1.58 Scores on a Scale | Standard Deviation 13.27 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 24 Day 168 (SQLS Cognition & Vitality Score) | -4.32 Scores on a Scale | Standard Deviation 13.59 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Week 12 Day 84 (SQLS Total Score) | 0.57 Scores on a Scale | Standard Deviation 12.98 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Schizophrenia Quality of Life Scale (SQLS) | Baseline (SQLS Psychosocial Score) | 30.84 Scores on a Scale | Standard Deviation 20.88 |
Comparison: Week 12 Day 84 (SQLS Cognition \& Vitality Score)p-value: 0.14290% CI: [-0.4, 6.95]Mixed Models Analysis
Comparison: Week 24 Day 168 (SQLS Cognition \& Vitality Score)p-value: 0.41690% CI: [-7.04, 2.4]Mixed Models Analysis
Comparison: Week 12 Day 84 (SQLS Psychosocial Score)p-value: 0.39490% CI: [-1.86, 5.83]Mixed Models Analysis
Comparison: Week 24 Day 168 (SQLS Psychosocial Score)p-value: 0.77690% CI: [-3.44, 4.87]Mixed Models Analysis
Comparison: Week 12 Day 84 (SQLS Total Score)p-value: 0.25490% CI: [-1.09, 5.94]Mixed Models Analysis
Comparison: Week 24 Day 168 (SQLS Total Score)p-value: 0.81690% CI: [-4.64, 3.5]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score
Logical memory (LM) assesses narrative memory under free-recall conditions. Two short stories are presented orally. The examinee is asked to retell each story from memory immediately after hearing it (LM I). In the delayed condition (LM II), the examinee is asked to retell both stories from the immediate condition (delayed free recall). Data is presented here for 2 Scores: LM I total raw score and LM II total raw score. The total raw score range is from 0 to 50 with larger total raw scores indicating better performance.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Baseline (LM I) | 16.55 Scores on a Scale | Standard Deviation 5.8 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 12 Day 84 (LM I) | -2.60 Scores on a Scale | Standard Deviation 5.33 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 24 Day 168 (LM I) | -3.02 Scores on a Scale | Standard Deviation 4.96 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Baseline (LM II) | 13.72 Scores on a Scale | Standard Deviation 6.57 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 12 Day 84 (LM II) | -2.91 Scores on a Scale | Standard Deviation 6.04 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 24 Day 168 (LM II) | -2.73 Scores on a Scale | Standard Deviation 4.94 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 12 Day 84 (LM II) | -2.63 Scores on a Scale | Standard Deviation 6.08 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Baseline (LM I) | 16.22 Scores on a Scale | Standard Deviation 8.13 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Baseline (LM II) | 14.29 Scores on a Scale | Standard Deviation 8.22 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 12 Day 84 (LM I) | -0.83 Scores on a Scale | Standard Deviation 5.66 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 24 Day 168 (LM II) | -3.22 Scores on a Scale | Standard Deviation 5.15 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Logical Memory Test (WMS IV-LM) Score | Week 24 Day 168 (LM I) | -2.29 Scores on a Scale | Standard Deviation 5.29 |
Comparison: Week 12 Day 84 (LM I)p-value: 0.16490% CI: [-0.27, 3.17]Mixed Models Analysis
Comparison: Week 24 Day 168 (LM I)p-value: 0.55990% CI: [-1.02, 2.14]Mixed Models Analysis
Comparison: Week 12 Day 84 (LM II)p-value: 0.91290% CI: [-1.7, 1.94]Mixed Models Analysis
Comparison: Week 24 Day 168 (LM II)p-value: 0.70690% CI: [-1.93, 1.22]Mixed Models Analysis
Secondary
Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score
The Paired Associates Learning (PAL I and II) of the WMS-IV (Wechsler Memory Scale Fourth edition) is a test of verbal learning and memory that requires the participant to learn novel word pairs. The participant learns the word pairs across learning trials and is asked to recall them immediately (PAL I) or after a 30-minute delay (PAL II). Data is presented here for 3 Scores: VPA I total raw score, VPA II total raw score and VPA II Recognition total raw score. The total raw score ranges for these 3 Scores are 0 to 56, 0 to 14 and 0 to 40 respectively, with larger total raw scores indicating better performance.
Time frame: Baseline up to Week 24
Population: The EAP2 Population was defined as all participants in the Efficacy Analysis Population (EAP) who were randomized to placebo or 240mg Basmisanil (excluded participants randomized to 80mg Basmisanil due to the results of a futility analysis which meant that enrolment into the 80mg Basmisanil arm was discontinued). Data presented below is only for participants that were included in the actual analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 12 Day 84 (VPA I total raw score) | 2.14 Scores on a Scale | Standard Deviation 6.55 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 24 Day 168 (VPA II total raw score) | 0.69 Scores on a Scale | Standard Deviation 2.16 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Baseline (VPA II total raw score) | 9.25 Scores on a Scale | Standard Deviation 3.76 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Baseline (VPA II recognition total raw score) | 36.24 Scores on a Scale | Standard Deviation 5.37 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 24 Day 168 (VPA I total raw score) | 4.42 Scores on a Scale | Standard Deviation 6.58 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 12 Day 84 (VPA II recognition total raw score) | 0.48 Scores on a Scale | Standard Deviation 5.43 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 12 Day 84 (VPA II total raw score) | 0.12 Scores on a Scale | Standard Deviation 2.29 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 24 Day 168 (VPA II recognition total raw score) | 1.12 Scores on a Scale | Standard Deviation 5.6 |
| Placebo | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Baseline (VPA I total raw score) | 31.14 Scores on a Scale | Standard Deviation 12.53 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 24 Day 168 (VPA II recognition total raw score) | 0.36 Scores on a Scale | Standard Deviation 2.8 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Baseline (VPA I total raw score) | 32.30 Scores on a Scale | Standard Deviation 11.75 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 12 Day 84 (VPA I total raw score) | 0.36 Scores on a Scale | Standard Deviation 7.33 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 24 Day 168 (VPA I total raw score) | 5.09 Scores on a Scale | Standard Deviation 6.4 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Baseline (VPA II total raw score) | 9.77 Scores on a Scale | Standard Deviation 3.54 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 12 Day 84 (VPA II total raw score) | 0.26 Scores on a Scale | Standard Deviation 2.15 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 24 Day 168 (VPA II total raw score) | 1.60 Scores on a Scale | Standard Deviation 2.33 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Baseline (VPA II recognition total raw score) | 37.36 Scores on a Scale | Standard Deviation 5.12 |
| Basmisanil 240mg BID | Change From Baseline to Week 24 in Wechsler Memory Scale Fourth Edition, Verbal Paired Associates (WMS IV-PAL) Score | Week 12 Day 84 (VPA II recognition total raw score) | -0.55 Scores on a Scale | Standard Deviation 2.92 |
Comparison: Week 12 Day 84 (VPA I total raw score)p-value: 0.21190% CI: [-3.78, 0.52]Mixed Models Analysis
Comparison: Week 24 Day 168 (VPA I total raw score)p-value: 0.78790% CI: [-1.81, 2.52]Mixed Models Analysis
Comparison: Week 12 Day 84 (VPA II total raw score)p-value: 0.47790% CI: [-0.37, 0.94]Mixed Models Analysis
Comparison: Week 24 Day 168 (VPA II total raw score)p-value: 0.02890% CI: [0.23, 1.58]Mixed Models Analysis
Comparison: Week 12 Day 84 (VPA II recognition total raw score)p-value: 0.68390% CI: [-1.51, 0.91]Mixed Models Analysis
Comparison: Week 24 Day 168 (VPA II recognition total raw score)p-value: 0.95490% CI: [-1.13, 1.22]Mixed Models Analysis
Secondary
Maximum Plasma Concentration of Basmisanil at Steady State (Cmax,ss)
Population PK model estimated maximum plasma concentration of Basmisanil at steady-state (ss).
Time frame: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168
Population: The Safety-evaluable population was defined as all participants who received at least one dose of study medication, whether prematurely withdrawn from the study or not. Data are summarized according to actual treatment arm participants were randomized to. Data presented below is only for participants included in the actual analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Maximum Plasma Concentration of Basmisanil at Steady State (Cmax,ss) | 2079 ng/mL |
| Basmisanil 240mg BID | Maximum Plasma Concentration of Basmisanil at Steady State (Cmax,ss) | 4374 ng/mL |
Secondary
Percentage of Participants With Adverse Events (AEs)
An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.
Time frame: Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
Population: The Safety-evaluable population was defined as all participants who received at least one dose of study medication, whether prematurely withdrawn from the study or not. Data are summarized according to actual treatment arm participants were randomized to.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events (AEs) | 39.5 Percentage of Participants |
| Basmisanil 240mg BID | Percentage of Participants With Adverse Events (AEs) | 46.3 Percentage of Participants |
| Basmisanil 240mg BID | Percentage of Participants With Adverse Events (AEs) | 48.7 Percentage of Participants |