Schizophrenia and Predominant Negative Symptoms
Conditions
Keywords
Schizophrenia
Brief summary
To explore the efficacy of SPD489, as adjunctive therapy to a stable dose of atypical antipsychotic medication, on negative symptoms in adult subjects with clinically stable schizophrenia and predominant negative symptoms, as measured by the Scale for the Assessment of Negative Symptoms (SANS).
Interventions
oral, 20, 30, 40, 50, 60, or 70 mg once daily
DRUGPlacebo matching SPD489 (lisdexamfetamine dimesylate)
oral, once daily
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 18-55 * Clinically stable Schizophrenia and predominant negative symptoms * Taking a stable dose of antipsychotic medication
Exclusion criteria
* Clinically notable positive symptoms defined by PANSS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Open-label Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Week 10 Open-label Phase, Last Observation Carried Forward (LOCF) | Open-label Baseline and Week 10 Open-label Phase | The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment. |
| Change From Double-blind Randomization Baseline in SANS-18 Total Score at Week 4 Double-blind Phase, Termination Observation Carried Forward (TOCF) | Double-blind Randomization Baseline and Week 4 Double-blind Phase | The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants In Double-blind Phase Who Maintained SANS-18 Response at Week 4 Double-blind Phase | Week 4 Double-blind Phase | Response is defined as reduction in total SANS score of greater than or equal to 20%. The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment. |
| Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase | Open-label Baseline and Week 10 Open-label Phase | The SANS assesses 5 symptom complexes to rate the negative symptoms of subjects. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment. |
| Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Double-blind Randomization Baseline and Week 4 Double-blind Phase | The SANS assesses 5 symptom complexes to rate the negative symptoms of subjects. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment. |
| Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF | Open-label Baseline and Week 10 Open-label Phase | The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment. |
| Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF | Double-blind Randomization Baseline and Week 4 Double-blind Phase | The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment. |
| Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Open-label Baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Percent of Participants With CGI-S at Week 10 Open-label Phase | Week 10 Open-label Phase | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Percent of Participants With CGI-S at Double-blind Randomization Baseline | Double-blind Randomization Baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Percent of Participants With CGI-S at Week 4 Double-blind Phase | Week 4 Double-blind Phase | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Percent of Participants With Improvement on Clinical Global Impression - Change (CGI-C) at Week 10 Open-label Phase | Open-label Phase Week 10 | CGI-C permits a global evaluation of the change of the subject's overall schizophrenia condition over time. It consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. |
| Percent of Participants With Improvement on CGI-C at Week 4 Double-blind Phase | Double-blind Phase Week 4 | CGI-C permits a global evaluation of the change of the subject's overall schizophrenia condition over time. It consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. |
| Change From Open-label Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Total Score at Week 10 Open-label Phase | Open-label Baseline and week 10 Open-label Phase | BACS measures attention and speed of processing, and the test score is the total number correct. The measure of the test is the number of correct numerals where subjects write numerals 1-9 as matches to nonmeaningful symbols on a response sheet for 90 seconds, based upon a key provided to them. |
| Change From Double-blind Randomization Baseline in BACS Total Score at Week 4 Double-blind Phase | Double-blind Randomization Baseline and Week 4 | BACS measures attention and speed of processing, and the test score is the total number correct. The measure of the test is the number of correct numerals where subjects write numerals 1-9 as matches to nonmeaningful symbols on a response sheet for 90 seconds, based upon a key provided to them. |
| Change From Open-label Baseline in Letter-Number Span Test (LNS) Total Score at Week 10 Open-label Phase | Open-label Baseline and week 10 Open-label Phase | LNS is a test of verbal working memory. Subjects are presented with a sequence of numbers and letters aurally and then asked to tell the rater the numbers first from lowest to highest followed by the letters in alphabetical sequence. The measure is the number of correct sequences. |
| Change From Double-blind Randomization Baseline in LNS Total Score at Week 4 Double-blind Phase | Double-blind Randomization Baseline and Week 4 | LNS is a test of verbal working memory. Subjects are presented with a sequence of numbers and letters aurally and then asked to tell the rater the numbers first from lowest to highest followed by the letters in alphabetical sequence. The measure is the number of correct sequences. |
| Percent of Participants In Open-label Phase Who Were SANS-18 Responders at Week 10 Open-label Phase | Week 10 Open-label Phase | Response is defined as reduction in total SANS score of greater than or equal to 20%. The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment. |
| Change From Double-blind Randomization Baseline in HVLT-R Total Scores at Week 4 Double-blind Phase | Double-blind Randomization Baseline and week 4 Double-blind Phase | HVLT-R measures verbal learning. Test scores are the total number of words recalled correctly over 3 trials. The test consists of 12 nouns read aloud for 3 consecutive trials and each trial is followed by a recall test. |
| Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF | Open-label Baseline and week 10 Open-label Phase | UPSA-B assesses skills in 5 areas of life functioning. It contains 2 subscales. Percentages correct on these 2 subscales are multiplied by 50. Thus, scores can range from 0 to 50 on each of these 2 subscales, and total scores can range from 0 to 100. Scores of 75 or higher are associated with independent living. |
| Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase | Double-blind Randomization Baseline and Week 4 Double-blind Phase | UPSA-B assesses skills in 5 areas of life functioning. It contains 2 subscales. Percentages correct on these 2 subscales are multiplied by 50. Thus, scores can range from 0 to 50 on each of these 2 subscales, and total scores can range from 0 to 100. Scores of 75 or higher are associated with independent living. |
| Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase | Open-label Baseline and Week 10 Open-label Phase | BRIEF-A is a validated 75-item questionnaire composed of three indexes (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase | Double-blind Randomization Baseline and Week 4 Double-blind Phase | BRIEF-A is a validated 75-item questionnaire composed of three indexes (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change From Open-label Baseline in Simpson Angus Scale (SAS) Total Score at Week 10 Open-label Phase | Open-label Baseline and Week 10 Open-label Phase | SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment. |
| Change From Open-label Baseline in SAS Total Score at Week 4 of Double-blind Phase | Open-label Baseline and Week 4 Double-blind Phase | SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment. |
| Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase | Open-label Baseline and week 10 Open-label Phase | BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness. |
| Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase | Open-label Baseline and Week 4 Double-blind Phase | BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness. |
| Change From Open-label Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at Week 10 Open-label Phase | Open-label Baseline and Week 10 Open-label Phase | ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity. |
| Change From Open-label Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Global Score at Week 10 Open-label Phase | Open-label Baseline and Week 10 Open-label Phase | PSQI evaluates 7 areas of quality and pattern of sleep. Each area is rated on a scale from 0 (better) to 3 (worse) with a total score ranging from 0 to 21. Reduction in total scores are associated with better sleep quality. |
| Change From Open-label Baseline in PSQI Total Global Score at Week 4 of Double-blind Phase | Open-label Baseline and Week 4 Double-blind Phase | PSQI evaluates 7 areas of quality and pattern of sleep. Each area is rated on a scale from 0 (better) to 3 (worse) with a total score ranging from 0 to 21. Reduction in total scores are associated with better sleep quality. |
| Change From Open-label Baseline in Calgary Depression Scale for Schizophrenia (CDSS) at Week 10 Open-label Phase | Open-label Baseline and Week 10 Open-label Phase | CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression. |
| Change From Open-label Baseline in CDSS at Week 4 of Double-blind Phase | Open-label Baseline and Week 4 of Double-blind Phase | CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression. |
| Change From Open-label Baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) Total Score at Week 10 Open-label Phase | Open-label Baseline and Week 10 | HVLT-R measures verbal learning. Test scores are the total number of words recalled correctly over 3 trials. The test consists of 12 nouns read aloud for 3 consecutive trials and each trial is followed by a recall test. |
| Change From Double-blind Randomization Baseline in ACSA Total Score at Week 4 Double-blind Phase | Double-blind Randomization Baseline and Week 4 Double-blind Phase | ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity. |
Countries
United States
Participant flow
Pre-assignment details
The study consisted of a 10-week Open-label Phase (7-week Dose Optimization Period and a 3-week Dose maintenance Period) in which subjects received 20 to 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily. They were then randomized into the Double-Blind Phase receiving either their optimal dose of SPD489 or placebo once-daily for 4 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Overall Constitutes all subjects contained in the Safety Analysis Set defined as all subjects who took at least 1 dose of open-label investigational product and for whom at least 1 follow-up safety assessment was made. | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Phase | Adverse Event | 1 | 1 |
| Double-blind Phase | Lost to Follow-up | 2 | 1 |
| Double-blind Phase | Noncompliance | 1 | 1 |
| Double-blind Phase | Positive urine drug screen | 1 | 1 |
| Double-blind Phase | Withdrawal by Subject | 1 | 1 |
| Double-blind Phase | Withdrawal criteria met | 1 | 1 |
| Open-label Phase | Adverse Event | 5 | 0 |
| Open-label Phase | Failure to meet randomization criteria | 1 | 0 |
| Open-label Phase | Protocol Violation | 1 | 0 |
| Open-label Phase | Withdrawal by Subject | 11 | 0 |
| Open-label Phase | Withdrawal criteria met | 5 | 0 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 9.11 |
| Age, Customized <18 years | 0 Participants |
| Age, Customized >55 years | 0 Participants |
| Age, Customized Between 18 and 55 years | 92 Participants |
| Region of Enrollment United States | 92 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 56 / 92 | 11 / 34 | 7 / 35 |
| serious Total, serious adverse events | 3 / 92 | 1 / 34 | 2 / 35 |
Outcome results
Primary
Change From Double-blind Randomization Baseline in SANS-18 Total Score at Week 4 Double-blind Phase, Termination Observation Carried Forward (TOCF)
The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.
Time frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase
Population: Randomized Evaluable Set (RES) defined as all randomized subjects who were responders (Response is defined as reduction in total SANS score of greater than or equal to 20%) at the Double-blind Randomization and had SANS-18 total scores at week 4 of the Double-blind Phase or the early termination visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in SANS-18 Total Score at Week 4 Double-blind Phase, Termination Observation Carried Forward (TOCF) | 4.5 Units on a scale | Standard Error 2.14 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in SANS-18 Total Score at Week 4 Double-blind Phase, Termination Observation Carried Forward (TOCF) | 2.2 Units on a scale | Standard Error 1.85 |
p-value: 0.418295% CI: [-3.4, 8.1]ANCOVA
Primary
Change From Open-label Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Week 10 Open-label Phase, Last Observation Carried Forward (LOCF)
The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: Open-label Phase Full Analysis Set (FAS) defined as all enrolled subjects who took at least 1 dose of the investigational product and had 1 primary efficacy assessment after baseline in the Open-label Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS-18) Total Score at Week 10 Open-label Phase, Last Observation Carried Forward (LOCF) | -12.9 Units on a scale | Standard Deviation 10.04 |
p-value: <0.0001t-test, 2 sided
Secondary
Change From Double-blind Randomization Baseline in ACSA Total Score at Week 4 Double-blind Phase
ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity.
Time frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase
Population: Randomized SAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in ACSA Total Score at Week 4 Double-blind Phase | 0.4 Units on a scale | Standard Deviation 7.65 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in ACSA Total Score at Week 4 Double-blind Phase | -2.9 Units on a scale | Standard Deviation 8.75 |
Secondary
Change From Double-blind Randomization Baseline in BACS Total Score at Week 4 Double-blind Phase
BACS measures attention and speed of processing, and the test score is the total number correct. The measure of the test is the number of correct numerals where subjects write numerals 1-9 as matches to nonmeaningful symbols on a response sheet for 90 seconds, based upon a key provided to them.
Time frame: Double-blind Randomization Baseline and Week 4
Population: Randomized FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in BACS Total Score at Week 4 Double-blind Phase | 0.1 correct numerals | Standard Error 1.19 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in BACS Total Score at Week 4 Double-blind Phase | -2.7 correct numerals | Standard Error 1.21 |
p-value: 0.107295% CI: [-0.6, 6.2]ANCOVA
Secondary
Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase
BRIEF-A is a validated 75-item questionnaire composed of three indexes (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase
Population: Randomized FAS
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase | Global Executive Composite | -1.7 T-scores | Standard Error 1.19 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase | Behavioral Recognition Index | -0.9 T-scores | Standard Error 1.22 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase | Metacognition Index | -2.0 T-scores | Standard Error 1.26 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase | Global Executive Composite | -1.2 T-scores | Standard Error 1.12 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase | Behavioral Recognition Index | -1.6 T-scores | Standard Error 1.14 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase | Metacognition Index | -0.7 T-scores | Standard Error 1.18 |
Comparison: Global Executive Compositep-value: 0.741895% CI: [-3.8, 2.7]ANCOVA
Comparison: Behavioral Recognition Indexp-value: 0.642995% CI: [-2.6, 4.1]ANCOVA
Comparison: Metacognition Indexp-value: 0.436495% CI: [-4.8, 2.1]ANCOVA
Secondary
Change From Double-blind Randomization Baseline in HVLT-R Total Scores at Week 4 Double-blind Phase
HVLT-R measures verbal learning. Test scores are the total number of words recalled correctly over 3 trials. The test consists of 12 nouns read aloud for 3 consecutive trials and each trial is followed by a recall test.
Time frame: Double-blind Randomization Baseline and week 4 Double-blind Phase
Population: Randomized FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in HVLT-R Total Scores at Week 4 Double-blind Phase | -1.5 words recalled | Standard Error 1.01 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in HVLT-R Total Scores at Week 4 Double-blind Phase | 1.0 words recalled | Standard Error 1.01 |
p-value: 0.087495% CI: [-5.4, 0.4]ANCOVA
Secondary
Change From Double-blind Randomization Baseline in LNS Total Score at Week 4 Double-blind Phase
LNS is a test of verbal working memory. Subjects are presented with a sequence of numbers and letters aurally and then asked to tell the rater the numbers first from lowest to highest followed by the letters in alphabetical sequence. The measure is the number of correct sequences.
Time frame: Double-blind Randomization Baseline and Week 4
Population: Randomized FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in LNS Total Score at Week 4 Double-blind Phase | -0.1 correct sequences | Standard Error 1.26 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in LNS Total Score at Week 4 Double-blind Phase | 1.3 correct sequences | Standard Error 1.28 |
p-value: 0.434795% CI: [-5, 2.2]ANCOVA
Secondary
Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF
The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.
Time frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase
Population: Randomized FAS defined as all subjects who received randomized investigational product and had a SANS-18 total scores at week 4 or at the early termination visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF | Positive subscale | 0.5 Units on a scale | Standard Error 0.31 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF | Negative subscale | 0.9 Units on a scale | Standard Error 0.46 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF | General Psychopathology subscale | 0.9 Units on a scale | Standard Error 0.78 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF | Positive subscale | -0.1 Units on a scale | Standard Error 0.31 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF | Negative subscale | -0.1 Units on a scale | Standard Error 0.45 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF | General Psychopathology subscale | -0.9 Units on a scale | Standard Error 0.77 |
Comparison: Positive subscalep-value: 0.197595% CI: [-0.3, 1.5]ANCOVA
Comparison: Negative subscalep-value: 0.122895% CI: [-0.3, 2.3]ANCOVA
Comparison: General Psychopathology subscalep-value: 0.111595% CI: [-0.4, 3.9]ANCOVA
Secondary
Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase
The SANS assesses 5 symptom complexes to rate the negative symptoms of subjects. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.
Time frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase
Population: RES
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Alogia | 0.5 Units on a scale | Standard Error 0.21 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Anhedonia-Asociality | 0.3 Units on a scale | Standard Error 0.18 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Avolition-Apathy | 0.2 Units on a scale | Standard Error 0.16 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Attention | 0.4 Units on a scale | Standard Error 0.18 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Affective Flattening | 0.2 Units on a scale | Standard Error 0.17 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Attention | 0.3 Units on a scale | Standard Error 0.17 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Affective Flattening | 0.2 Units on a scale | Standard Error 0.15 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Alogia | 0.0 Units on a scale | Standard Error 0.19 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Avolition-Apathy | 0.1 Units on a scale | Standard Error 0.15 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase | Anhedonia-Asociality | 0.1 Units on a scale | Standard Error 0.16 |
Comparison: Affective Flatteningp-value: 0.877195% CI: [-0.4, 0.5]ANCOVA
Comparison: Alogiap-value: 0.058495% CI: [0, 1.1]ANCOVA
Comparison: Avolition-Apathyp-value: 0.521595% CI: [-0.3, 0.6]ANCOVA
Comparison: Anhedonia-Asocialityp-value: 0.483595% CI: [-0.3, 0.7]ANCOVA
Comparison: Attentionp-value: 0.572395% CI: [-0.4, 0.7]ANCOVA
Secondary
Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase
UPSA-B assesses skills in 5 areas of life functioning. It contains 2 subscales. Percentages correct on these 2 subscales are multiplied by 50. Thus, scores can range from 0 to 50 on each of these 2 subscales, and total scores can range from 0 to 100. Scores of 75 or higher are associated with independent living.
Time frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase
Population: Randomized FAS
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase | Total Skills | -1.5 Scores on a scale | Standard Error 1.35 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase | Communication Skills | -1.5 Scores on a scale | Standard Error 1.14 |
| SPD489 (Open-label Phase) | Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase | Financial Skills | -0.3 Scores on a scale | Standard Error 0.83 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase | Total Skills | 0.0 Scores on a scale | Standard Error 1.37 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase | Communication Skills | -0.6 Scores on a scale | Standard Error 1.16 |
| Placebo (Double-blind Phase) | Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase | Financial Skills | 0.9 Scores on a scale | Standard Error 0.84 |
Comparison: Total Skillsp-value: 0.463795% CI: [-5.3, 2.4]ANCOVA
Comparison: Communication Skillsp-value: 0.613795% CI: [-4.1, 2.4]ANCOVA
Comparison: Financial Skillsp-value: 0.348295% CI: [-3.5, 1.3]ANCOVA
Secondary
Change From Open-label Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at Week 10 Open-label Phase
ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: SAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at Week 10 Open-label Phase | -1.8 Units on a scale | Standard Deviation 9.69 |
Secondary
Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase
BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.
Time frame: Open-label Baseline and week 10 Open-label Phase
Population: SAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase | Objective | 0.0 Units on a scale | Standard Deviation 0.17 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase | Subjective | 0.0 Units on a scale | Standard Deviation 0.56 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase | Global | 0.0 Units on a scale | Standard Deviation 0.36 |
Secondary
Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase
BAS scale has objective, subjective, and global impression components of akathisia (motor restlessness that manifests itself with an inability to sit still or remain motionless). Objective and subjective components are rated on a scale from 0 (normal/absence) to 3 (severe) and are summed yielding a total score of 0 to 9. Global impression is rated on a scale from 0 (absent) to 5 (severe) with a total score ranging from 0 to 5. Lower scores indicate reduced restlessness.
Time frame: Open-label Baseline and Week 4 Double-blind Phase
Population: Randomized SAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase | Objective | 0.0 Units on a scale | Standard Deviation 0.18 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase | Subjective | 0.0 Units on a scale | Standard Deviation 0.31 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase | Global | 0.0 Units on a scale | Standard Deviation 0.18 |
| Placebo (Double-blind Phase) | Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase | Objective | -0.1 Units on a scale | Standard Deviation 0.24 |
| Placebo (Double-blind Phase) | Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase | Subjective | -0.1 Units on a scale | Standard Deviation 0.65 |
| Placebo (Double-blind Phase) | Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase | Global | -0.2 Units on a scale | Standard Deviation 0.44 |
Secondary
Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase
BRIEF-A is a validated 75-item questionnaire composed of three indexes (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase | Global Executive Composite | -3.9 T-scores | Standard Deviation 13.29 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase | Behavioral Recognition Index | -3.1 T-scores | Standard Deviation 12.89 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase | Metacognition Index | -3.9 T-scores | Standard Deviation 13.12 |
Comparison: Global Executive Compositep-value: 0.0174t-test, 2 sided
Comparison: Behavioral Recognition Indexp-value: 0.0461t-test, 2 sided
Comparison: Metacognition Indexp-value: 0.0146t-test, 2 sided
Secondary
Change From Open-label Baseline in Calgary Depression Scale for Schizophrenia (CDSS) at Week 10 Open-label Phase
CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: Safety Analysis Set (SAS) defined as all subjects who took at least 1 dose of open-label investigational product and for whom at least 1 follow-up safety assessment was made.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Calgary Depression Scale for Schizophrenia (CDSS) at Week 10 Open-label Phase | -0.7 Units on a scale | Standard Deviation 2.11 |
Secondary
Change From Open-label Baseline in CDSS at Week 4 of Double-blind Phase
CDSS is a 9-item scale to evaluate depression in subjects who have schizophrenia rated from 0 (absence of symptoms) to 3 (severe symptoms) with a total score range of 0 to 27. Lower scores indicate less depression.
Time frame: Open-label Baseline and Week 4 of Double-blind Phase
Population: Randomized SAS defined as all subjects who took at least 1 dose of randomized investigational product and for whom at least 1 follow-up safety assessment was made.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in CDSS at Week 4 of Double-blind Phase | -0.1 Units on a scale | Standard Deviation 2.34 |
| Placebo (Double-blind Phase) | Change From Open-label Baseline in CDSS at Week 4 of Double-blind Phase | -0.7 Units on a scale | Standard Deviation 2.3 |
Secondary
Change From Open-label Baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) Total Score at Week 10 Open-label Phase
HVLT-R measures verbal learning. Test scores are the total number of words recalled correctly over 3 trials. The test consists of 12 nouns read aloud for 3 consecutive trials and each trial is followed by a recall test.
Time frame: Open-label Baseline and Week 10
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) Total Score at Week 10 Open-label Phase | 0.7 words recalled | Standard Deviation 7.54 |
p-value: 0.4312t-test, 2 sided
Secondary
Change From Open-label Baseline in Letter-Number Span Test (LNS) Total Score at Week 10 Open-label Phase
LNS is a test of verbal working memory. Subjects are presented with a sequence of numbers and letters aurally and then asked to tell the rater the numbers first from lowest to highest followed by the letters in alphabetical sequence. The measure is the number of correct sequences.
Time frame: Open-label Baseline and week 10 Open-label Phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Letter-Number Span Test (LNS) Total Score at Week 10 Open-label Phase | 0.8 correct sequences | Standard Deviation 7.72 |
p-value: 0.366t-test, 2 sided
Secondary
Change From Open-label Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Global Score at Week 10 Open-label Phase
PSQI evaluates 7 areas of quality and pattern of sleep. Each area is rated on a scale from 0 (better) to 3 (worse) with a total score ranging from 0 to 21. Reduction in total scores are associated with better sleep quality.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: SAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Global Score at Week 10 Open-label Phase | -0.7 Units on a scale | Standard Deviation 3.15 |
Secondary
Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF
The PANSS is a validated measure that evaluates the presence, absence, and severity of 30 symptoms of schizophrenia including both positive and negative symptoms and general psychopathology. Each of the 30-items are rated on a scale of 1 (absent) to 7 (extreme) with a total scoring range of 30 to 210. Higher scores indicate more impairment.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF | Positive subscale | -1.0 Units on a scale | Standard Deviation 2.23 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF | Negative subscale | -4.8 Units on a scale | Standard Deviation 4.01 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF | General Psychopathology subscale | -4.0 Units on a scale | Standard Deviation 5.11 |
Comparison: Positive subscalep-value: <0.0001t-test, 2 sided
Comparison: Negative subscalep-value: <0.0001t-test, 2 sided
Comparison: General Psychopathology subscalep-value: <0.0001t-test, 2 sided
Secondary
Change From Open-label Baseline in PSQI Total Global Score at Week 4 of Double-blind Phase
PSQI evaluates 7 areas of quality and pattern of sleep. Each area is rated on a scale from 0 (better) to 3 (worse) with a total score ranging from 0 to 21. Reduction in total scores are associated with better sleep quality.
Time frame: Open-label Baseline and Week 4 Double-blind Phase
Population: Randomized SAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in PSQI Total Global Score at Week 4 of Double-blind Phase | 0.3 Units on a scale | Standard Deviation 3.01 |
| Placebo (Double-blind Phase) | Change From Open-label Baseline in PSQI Total Global Score at Week 4 of Double-blind Phase | -1.7 Units on a scale | Standard Deviation 3 |
Secondary
Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase
The SANS assesses 5 symptom complexes to rate the negative symptoms of subjects. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase | Affective Flattening | -0.9 Units on a scale | Standard Deviation 0.8 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase | Alogia | -0.9 Units on a scale | Standard Deviation 0.65 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase | Avolition-Apathy | -0.5 Units on a scale | Standard Deviation 0.81 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase | Anhedonia-Asociality | -0.7 Units on a scale | Standard Deviation 0.77 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase | Attention | -0.7 Units on a scale | Standard Deviation 0.8 |
Comparison: Affective Flatteningp-value: <0.0001t-test, 2 sided
Comparison: Alogiap-value: <0.0001t-test, 2 sided
Comparison: Avolition-Apathyp-value: <0.0001t-test, 2 sided
Comparison: Anhedonia-Asocialityp-value: <0.0001t-test, 2 sided
Comparison: Attentionp-value: <0.0001t-test, 2 sided
Secondary
Change From Open-label Baseline in SAS Total Score at Week 4 of Double-blind Phase
SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.
Time frame: Open-label Baseline and Week 4 Double-blind Phase
Population: Randomized SAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in SAS Total Score at Week 4 of Double-blind Phase | 0.00 Units on a scale | Standard Deviation 0.093 |
| Placebo (Double-blind Phase) | Change From Open-label Baseline in SAS Total Score at Week 4 of Double-blind Phase | 0.00 Units on a scale | Standard Deviation 0.043 |
Secondary
Change From Open-label Baseline in Simpson Angus Scale (SAS) Total Score at Week 10 Open-label Phase
SAS is a 10-item scale used to evaluate the presence and severity of extrapyramidal symptoms. The items are scored on a scale from 0 to 4 with item-specific definitions given for each point. Total scores range from 0 to 40. Lower scores indicate less impairment.
Time frame: Open-label Baseline and Week 10 Open-label Phase
Population: SAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in Simpson Angus Scale (SAS) Total Score at Week 10 Open-label Phase | -0.01 Units on a scale | Standard Deviation 0.063 |
Secondary
Change From Open-label Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Total Score at Week 10 Open-label Phase
BACS measures attention and speed of processing, and the test score is the total number correct. The measure of the test is the number of correct numerals where subjects write numerals 1-9 as matches to nonmeaningful symbols on a response sheet for 90 seconds, based upon a key provided to them.
Time frame: Open-label Baseline and week 10 Open-label Phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Total Score at Week 10 Open-label Phase | 2.3 correct numerals | Standard Deviation 8.92 |
p-value: 0.0307t-test, 2 sided
Secondary
Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF
UPSA-B assesses skills in 5 areas of life functioning. It contains 2 subscales. Percentages correct on these 2 subscales are multiplied by 50. Thus, scores can range from 0 to 50 on each of these 2 subscales, and total scores can range from 0 to 100. Scores of 75 or higher are associated with independent living.
Time frame: Open-label Baseline and week 10 Open-label Phase
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD489 (Open-label Phase) | Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF | Total Skills | 6.2 Scores on a scale | Standard Deviation 12.2 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF | Communication Skills | 3.7 Scores on a scale | Standard Deviation 8.56 |
| SPD489 (Open-label Phase) | Change From Open-label Baseline in University of California Performance-Based Skills Assessment, Brief Version (UPSA-B) Scores at Week 10 Open-label Phase, LOCF | Financial Skills | 2.5 Scores on a scale | Standard Deviation 7.45 |
Comparison: Total Skillsp-value: <0.0001t-test, 2 sided
Comparison: Communication Skillsp-value: 0.0002t-test, 2 sided
Comparison: Financial Skillsp-value: 0.0028t-test, 2 sided
Secondary
Percent of Participants In Double-blind Phase Who Maintained SANS-18 Response at Week 4 Double-blind Phase
Response is defined as reduction in total SANS score of greater than or equal to 20%. The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.
Time frame: Week 4 Double-blind Phase
Population: RES
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants In Double-blind Phase Who Maintained SANS-18 Response at Week 4 Double-blind Phase | 71.4 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants In Double-blind Phase Who Maintained SANS-18 Response at Week 4 Double-blind Phase | 82.4 Percent of participants |
p-value: 0.6705Fisher Exact
Secondary
Percent of Participants In Open-label Phase Who Were SANS-18 Responders at Week 10 Open-label Phase
Response is defined as reduction in total SANS score of greater than or equal to 20%. The SANS was modified by eliminating the global and attention items; the score of the remaining non-global items is referred to as the SANS-18 total score. Each of the 18-items is scored on a scale from 0 (not at all) to 5 (severe) with a total scoring range of 0 to 90. Higher scores indicate more impairment.
Time frame: Week 10 Open-label Phase
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants In Open-label Phase Who Were SANS-18 Responders at Week 10 Open-label Phase | 52.9 Percent of participants |
Secondary
Percent of Participants With CGI-S at Double-blind Randomization Baseline
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Double-blind Randomization Baseline
Population: Randomized FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Mildly ill | 50.0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Markedly ill | 8.8 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Borderline mentally ill | 2.9 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Severely ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Moderately ill | 38.2 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Among the most extremely ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Normal, not at all ill | 0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Among the most extremely ill | 0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Normal, not at all ill | 0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Borderline mentally ill | 2.9 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Mildly ill | 60.0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Moderately ill | 37.1 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Markedly ill | 0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Double-blind Randomization Baseline | Severely ill | 0 Percent of participants |
Secondary
Percent of Participants With CGI-S at Week 10 Open-label Phase
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Week 10 Open-label Phase
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 10 Open-label Phase | Normal, not at all ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 10 Open-label Phase | Borderline mentally ill | 2.9 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 10 Open-label Phase | Mildly ill | 54.3 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 10 Open-label Phase | Moderately ill | 38.6 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 10 Open-label Phase | Markedly ill | 4.3 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 10 Open-label Phase | Severely ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 10 Open-label Phase | Among the most extremely ill | 0 Percent of participants |
Secondary
Percent of Participants With CGI-S at Week 4 Double-blind Phase
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Week 4 Double-blind Phase
Population: Randomized FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Mildly ill | 34.5 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Markedly ill | 13.8 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Borderline mentally ill | 3.4 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Severely ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Moderately ill | 48.3 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Among the most extremely ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Normal, not at all ill | 0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Among the most extremely ill | 0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Normal, not at all ill | 0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Borderline mentally ill | 13.8 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Mildly ill | 69.0 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Moderately ill | 13.8 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Markedly ill | 3.4 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With CGI-S at Week 4 Double-blind Phase | Severely ill | 0 Percent of participants |
Secondary
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Open-label Baseline
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Normal, not at all ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Borderline mentally ill | 0 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Mildly ill | 29.3 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Moderately ill | 55.4 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Markedly ill | 14.1 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Severely ill | 1.1 Percent of participants |
| SPD489 (Open-label Phase) | Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline | Among the most extremely ill | 0 Percent of participants |
Secondary
Percent of Participants With Improvement on CGI-C at Week 4 Double-blind Phase
CGI-C permits a global evaluation of the change of the subject's overall schizophrenia condition over time. It consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time frame: Double-blind Phase Week 4
Population: Randomized FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants With Improvement on CGI-C at Week 4 Double-blind Phase | 17.2 Percent of participants |
| Placebo (Double-blind Phase) | Percent of Participants With Improvement on CGI-C at Week 4 Double-blind Phase | 27.6 Percent of participants |
Secondary
Percent of Participants With Improvement on Clinical Global Impression - Change (CGI-C) at Week 10 Open-label Phase
CGI-C permits a global evaluation of the change of the subject's overall schizophrenia condition over time. It consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time frame: Open-label Phase Week 10
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SPD489 (Open-label Phase) | Percent of Participants With Improvement on Clinical Global Impression - Change (CGI-C) at Week 10 Open-label Phase | 30.0 Percent of participants |