Efficacy, Safety, and Tolerability of SPD489 in Adults With Schizophrenia and Predominant Negative Symptoms

Study Overview
=================
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).

Official Title
-----------------
A Phase 2, Multicenter Study With Open-label & Randomized Double-blind Placebo-controlled Withdrawal Phases to Evaluate the Efficacy, Safety, & Tolerability of SPD489 in Adults With Schizophrenia & Predominant Negative Symptoms Who Are Clinically Stable & Taking Stable Doses of Atypical Antipsychotic Medication

Conditions
-----------------
Schizophrenia and Predominant Negative Symptoms

Intervention / Treatment
-----------------
* Drug: SPD489 (lisdexamfetamine dimesylate)
* Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD489 (Lisdexamfetamine dimesylate)<br> | Drug: SPD489 (lisdexamfetamine dimesylate)<br>* oral, 20, 30, 40, 50, 60, or 70 mg once daily<br>* Other names: Vyvanse;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)<br>* oral, once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Open-label Baseline and Week 10 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) | 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. | Double-blind Randomization Baseline and Week 4 Double-blind Phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 10 Open-label Phase | 
| 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. | Week 4 Double-blind Phase | 
| 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. | Open-label Baseline and Week 10 Open-label Phase | 
| 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. | Double-blind Randomization Baseline and Week 4 Double-blind Phase | 
| 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. | Open-label Baseline and Week 10 Open-label Phase | 
| 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. | Double-blind Randomization Baseline and Week 4 Double-blind Phase | 
| 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) | Open-label Baseline | 
| 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) | Week 10 Open-label Phase | 
| 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) | Double-blind Randomization Baseline | 
| 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) | Week 4 Double-blind Phase | 
| 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. | Open-label Phase Week 10 | 
| 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. | Double-blind Phase Week 4 | 
| 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. | Open-label Baseline and week 10 Open-label Phase | 
| 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. | Double-blind Randomization Baseline and Week 4 | 
| 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. | Open-label Baseline and week 10 Open-label Phase | 
| 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. | Double-blind Randomization Baseline and Week 4 | 
| 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. | Open-label Baseline and Week 10 | 
| 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. | Double-blind Randomization Baseline and week 4 Double-blind 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 | 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. | Open-label Baseline and week 10 Open-label Phase | 
| 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. | Double-blind Randomization Baseline and Week 4 Double-blind 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 | 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. | Open-label Baseline and Week 10 Open-label Phase | 
| 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. | Double-blind Randomization Baseline and Week 4 Double-blind Phase | 
| 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. | Open-label Baseline and Week 10 Open-label Phase | 
| 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. | Open-label Baseline and Week 4 Double-blind Phase | 
| 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. | Open-label Baseline and week 10 Open-label Phase | 
| 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. | Open-label Baseline and Week 4 Double-blind Phase | 
| 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. | Open-label Baseline and Week 10 Open-label Phase | 
| 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. | Double-blind Randomization Baseline and Week 4 Double-blind Phase | 
| 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. | Open-label Baseline and Week 10 Open-label Phase | 
| 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. | Open-label Baseline and Week 4 Double-blind Phase | 
| 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. | Open-label Baseline and Week 10 Open-label Phase | 
| 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. | Open-label Baseline and Week 4 of Double-blind Phase | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia