Trial Outcomes & Findings for A Study to Evaluate the Effects of Basmisanil in Participants With Cognitive Impairment Associated With Schizophrenia (CIAS) Treated With Antipsychotics (NCT NCT02953639)
NCT ID: NCT02953639
Last Updated: 2021-02-09
Results Overview
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.
COMPLETED
PHASE2
214 participants
Baseline up to Week 24
2021-02-09
Participant Flow
The study was conducted at 37 centers in 1 country.
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.
Participant milestones
| Measure |
Placebo
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 80mg BID
Participants received Basmisanil 80 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
81
|
54
|
78
|
|
Overall Study
COMPLETED
|
61
|
40
|
62
|
|
Overall Study
NOT COMPLETED
|
20
|
14
|
16
|
Reasons for withdrawal
| Measure |
Placebo
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 80mg BID
Participants received Basmisanil 80 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
8
|
4
|
3
|
|
Overall Study
Non-Compliance With Study Drug
|
0
|
2
|
1
|
|
Overall Study
Multiple Reasons
|
1
|
0
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
7
|
8
|
10
|
|
Overall Study
Completed or Discontinued information is missing
|
1
|
0
|
0
|
Baseline Characteristics
A Study to Evaluate the Effects of Basmisanil in Participants With Cognitive Impairment Associated With Schizophrenia (CIAS) Treated With Antipsychotics
Baseline characteristics by cohort
| Measure |
Placebo
n=81 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 80mg BID
n=54 Participants
Participants received Basmisanil 80 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
n=78 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Total
n=213 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
36.4 Years
STANDARD_DEVIATION 8.2 • n=93 Participants
|
36.8 Years
STANDARD_DEVIATION 8.6 • n=4 Participants
|
37.4 Years
STANDARD_DEVIATION 8.4 • n=27 Participants
|
36.9 Years
STANDARD_DEVIATION 8.4 • n=483 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
50 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
61 Participants
n=93 Participants
|
42 Participants
n=4 Participants
|
60 Participants
n=27 Participants
|
163 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
13 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
32 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
68 Participants
n=93 Participants
|
47 Participants
n=4 Participants
|
66 Participants
n=27 Participants
|
181 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
51 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
51 Participants
n=27 Participants
|
132 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
MULTIPLE
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
UNKNOWN
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White
|
25 Participants
n=93 Participants
|
23 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
71 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
32.36 Composite T-Score
Standard Deviation 11.44
|
—
|
|
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
|
-0.28 Composite T-Score
Standard Deviation 6.08
|
—
|
|
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
|
1.36 Composite T-Score
Standard Deviation 4.80
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Baseline (Attention/Vigilance)
|
40.75 T-score
Standard Deviation 12.31
|
39.66 T-score
Standard Deviation 12.08
|
—
|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Week 12 Day 84 (Attention/Vigilance)
|
-0.16 T-score
Standard Deviation 8.00
|
-0.14 T-score
Standard Deviation 8.80
|
—
|
|
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
|
0.51 T-score
Standard Deviation 8.49
|
—
|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Baseline (Reasoning and Problem Solving)
|
42.75 T-score
Standard Deviation 12.61
|
43.71 T-score
Standard Deviation 10.12
|
—
|
|
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
|
0.05 T-score
Standard Deviation 6.07
|
—
|
|
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
|
2.18 T-score
Standard Deviation 6.13
|
—
|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Baseline (Social Cognition)
|
37.79 T-score
Standard Deviation 13.30
|
38.38 T-score
Standard Deviation 13.09
|
—
|
|
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
|
-0.62 T-score
Standard Deviation 8.55
|
—
|
|
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
|
0.96 T-score
Standard Deviation 7.10
|
—
|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Baseline (Speed of Processing)
|
37.08 T-score
Standard Deviation 13.10
|
37.81 T-score
Standard Deviation 12.70
|
—
|
|
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
|
-1.66 T-score
Standard Deviation 6.07
|
—
|
|
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
|
0.13 T-score
Standard Deviation 4.88
|
—
|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Baseline (Verbal Learning)
|
37.34 T-score
Standard Deviation 9.20
|
36.53 T-score
Standard Deviation 7.41
|
—
|
|
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
|
0.45 T-score
Standard Deviation 7.01
|
—
|
|
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
|
0.36 T-score
Standard Deviation 6.53
|
—
|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Baseline (Visual Learning)
|
35.96 T-score
Standard Deviation 12.18
|
35.38 T-score
Standard Deviation 11.98
|
—
|
|
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
|
-0.48 T-score
Standard Deviation 9.35
|
—
|
|
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
|
0.53 T-score
Standard Deviation 9.33
|
—
|
|
Change From Baseline to Week 24 in MCCB Cognitive Domain Scores
Baseline (Working Memory)
|
35.99 T-score
Standard Deviation 12.56
|
36.23 T-score
Standard Deviation 10.09
|
—
|
|
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
|
0.76 T-score
Standard Deviation 6.41
|
—
|
|
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
|
1.76 T-score
Standard Deviation 6.68
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
32.30 Scores on a Scale
Standard Deviation 11.75
|
—
|
|
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
|
0.36 Scores on a Scale
Standard Deviation 7.33
|
—
|
|
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
|
5.09 Scores on a Scale
Standard Deviation 6.40
|
—
|
|
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
|
9.77 Scores on a Scale
Standard Deviation 3.54
|
—
|
|
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
|
0.26 Scores on a Scale
Standard Deviation 2.15
|
—
|
|
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
|
1.60 Scores on a Scale
Standard Deviation 2.33
|
—
|
|
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
|
37.36 Scores on a Scale
Standard Deviation 5.12
|
—
|
|
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
|
-0.55 Scores on a Scale
Standard Deviation 2.92
|
—
|
|
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 5.60
|
0.36 Scores on a Scale
Standard Deviation 2.80
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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 5.80
|
16.22 Scores on a Scale
Standard Deviation 8.13
|
—
|
|
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
|
-0.83 Scores on a Scale
Standard Deviation 5.66
|
—
|
|
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
|
-2.29 Scores on a Scale
Standard Deviation 5.29
|
—
|
|
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
|
14.29 Scores on a Scale
Standard Deviation 8.22
|
—
|
|
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
|
-2.63 Scores on a Scale
Standard Deviation 6.08
|
—
|
|
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
|
-3.22 Scores on a Scale
Standard Deviation 5.15
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
3.12 Ratio
Standard Deviation 1.58
|
—
|
|
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
|
-0.12 Ratio
Standard Deviation 1.34
|
—
|
|
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 2.00
|
-0.06 Ratio
Standard Deviation 1.22
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=74 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=76 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
60.88 Scores on a Scale
Standard Deviation 10.87
|
—
|
|
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 8.30
|
2.26 Scores on a Scale
Standard Deviation 8.68
|
—
|
|
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
|
4.14 Scores on a Scale
Standard Deviation 10.05
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
36.53 Scores on a Scale
Standard Deviation 9.84
|
—
|
|
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
|
-3.66 Scores on a Scale
Standard Deviation 5.78
|
—
|
|
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
|
-4.02 Scores on a Scale
Standard Deviation 7.79
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
Values for the CGI-S Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment.
Outcome measures
| Measure |
Placebo
n=75 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
-0.24 Scores on a Scale
Standard Deviation 0.60
|
—
|
|
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
|
2.39 Scores on a Scale
Standard Deviation 0.75
|
—
|
|
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
|
-0.29 Scores on a Scale
Standard Deviation 0.76
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
Values for the CGI-I Scale are encoded by the numerical values from 1 to 7 respectively. Higher numerical values represent greater impairment.
Outcome measures
| Measure |
Placebo
n=58 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=58 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
-0.45 Scores on a Scale
Standard Deviation 0.86
|
—
|
|
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
|
-0.64 Scores on a Scale
Standard Deviation 0.91
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=77 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
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
|
34.21 Scores on a Scale
Standard Deviation 18.59
|
—
|
|
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
|
0.21 Scores on a Scale
Standard Deviation 14.00
|
—
|
|
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
|
-4.32 Scores on a Scale
Standard Deviation 13.59
|
—
|
|
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
|
30.84 Scores on a Scale
Standard Deviation 20.88
|
—
|
|
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
|
0.80 Scores on a Scale
Standard Deviation 14.49
|
—
|
|
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
|
-1.58 Scores on a Scale
Standard Deviation 13.27
|
—
|
|
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
|
32.14 Scores on a Scale
Standard Deviation 19.19
|
—
|
|
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 11.80
|
0.57 Scores on a Scale
Standard Deviation 12.98
|
—
|
|
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
|
-2.66 Scores on a Scale
Standard Deviation 12.31
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=81 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=54 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
n=78 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
|
39.5 Percentage of Participants
|
46.3 Percentage of Participants
|
48.7 Percentage of Participants
|
SECONDARY outcome
Timeframe: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168Population: 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.
Population PK model estimated apparent oral clearance of Basmisanil at steady-state.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168Population: 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.
Population PK model estimated apparent volume of distribution of Basmisanil at steady-state.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168Population: 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.
Population PK model estimated AUC of Basmisanil at steady-state.
Outcome measures
| Measure |
Placebo
n=54 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=78 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Area Under the Curve of Basmisanil at Steady State (AUC,ss)
|
41640 ng*mL/hr
Interval 31464.0 to 51816.0
|
87624 ng*mL/hr
Interval 66504.0 to 108768.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (hour 0) in Days 7, 14, 42, 84, 168Population: 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.
Population PK model estimated maximum plasma concentration of Basmisanil at steady-state (ss).
Outcome measures
| Measure |
Placebo
n=54 Participants
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 240mg BID
n=78 Participants
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Maximum Plasma Concentration of Basmisanil at Steady State (Cmax,ss)
|
2079 ng/mL
Interval 1645.0 to 2513.0
|
4374 ng/mL
Interval 3455.0 to 5294.0
|
—
|
Adverse Events
Placebo
Basmisanil 80mg BID
Basmisanil 240mg BID
Serious adverse events
| Measure |
Placebo
n=81 participants at risk
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 80mg BID
n=54 participants at risk
Participants received Basmisanil 80 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
n=78 participants at risk
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Cardiac disorders
Supraventricular extrasystoles
|
1.2%
1/81 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/78 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Gastrointestinal disorders
Pancreatitis
|
1.2%
1/81 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/78 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/81 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
1.3%
1/78 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Metabolism and nutrition disorders
Diabetic complication
|
0.00%
0/81 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
1.3%
1/78 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Psychiatric disorders
Psychotic disorder
|
1.2%
1/81 • Number of events 2 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
2.6%
2/78 • Number of events 2 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Psychiatric disorders
Schizophrenia
|
1.2%
1/81 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/78 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Psychiatric disorders
Suicide attempt
|
1.2%
1/81 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/78 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
Other adverse events
| Measure |
Placebo
n=81 participants at risk
Participants received matching Placebo to Basmisanil orally twice daily for 24 weeks.
|
Basmisanil 80mg BID
n=54 participants at risk
Participants received Basmisanil 80 mg orally twice daily (BID) for 24 weeks.
|
Basmisanil 240mg BID
n=78 participants at risk
Participants received Basmisanil 240 mg orally twice daily (BID) for 24 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.9%
4/81 • Number of events 4 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
5.6%
3/54 • Number of events 4 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
2.6%
2/78 • Number of events 2 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
General disorders
Fatigue
|
7.4%
6/81 • Number of events 7 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
1.9%
1/54 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
1.3%
1/78 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/81 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
5.6%
3/54 • Number of events 3 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/78 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Nervous system disorders
Headache
|
1.2%
1/81 • Number of events 1 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
5.6%
3/54 • Number of events 3 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
9.0%
7/78 • Number of events 9 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
|
Nervous system disorders
Somnolence
|
0.00%
0/81 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
0.00%
0/54 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
5.1%
4/78 • Number of events 4 • Baseline up to 4 weeks after the last dose of study drug (up to 28 weeks)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER