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

Phase 2

Completed

Conditions: Schizophrenia and Predominant Negative Symptoms

Interventions: Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)
Drug: SPD489 (lisdexamfetamine dimesylate)

Registration Number: NCT00922272

Lead Sponsor: Shire

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 92

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo matching SPD489 (lisdexamfetamine dimesylate)	Placebo
SPD489 (Lisdexamfetamine dimesylate)	SPD489 (lisdexamfetamine dimesylate)	-

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.
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 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)
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 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 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 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 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 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.
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 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.
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 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 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.
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.
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)
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 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 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 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 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 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.
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.
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 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 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 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 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 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 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.
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.

Trial Locations

Locations (27): K&S Professional Research Services
🇺🇸
Little Rock, Arkansas, United States
CRI Worldwide, LLC.
🇺🇸
Willingboro, New Jersey, United States
Clinical Innovations
🇺🇸
Costa Mesa, California, United States
Neuropsychiatric Research Center of Orange County
🇺🇸
Santa Ana, California, United States
University Hills Clinical Research
🇺🇸
Irving, Texas, United States
CNRI San Diego & Los Angeles
🇺🇸
San Diego, California, United States
South Coast Clinical Trials
🇺🇸
Anaheim, California, United States
Collaborative Neuroscience Network, Inc.
🇺🇸
Garden Grove, California, United States
Excell Research, Inc.
🇺🇸
Oceanside, California, United States
Artemis Institute for Clinical Research
🇺🇸
San Diego, California, United States
Community Clinical Research, Inc.
🇺🇸
Austin, Texas, United States
Southcoast Clinical Trials
🇺🇸
San Bernardino, California, United States
Advanced Bio-Behavioral Sciences
🇺🇸
Elmsford, New York, United States
Comprehensive Neuroscience, Inc.
🇺🇸
Hollis, New York, United States
Omega Clinical Trials
🇺🇸
Anaheim, California, United States
Accurate Clinical Trials
🇺🇸
Kissimmee, Florida, United States
CRI Worldwide
🇺🇸
Philadelphia, Pennsylvania, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Behavioral Clinical Research, INC
🇺🇸
Lauderhill, Florida, United States
Stedman Clinical Trials
🇺🇸
Tampa, Florida, United States
Comprehensive NeuroScience
🇺🇸
Atlanta, Georgia, United States
J. Gary Booker, MD, APMC
🇺🇸
Shreveport, Louisiana, United States
Apostle Clinical Trials, Inc.
🇺🇸
Long Beach, California, United States
Affiliated Research Institute
🇺🇸
San Diego, California, United States
Uptown Research Institute
🇺🇸
Chicago, Illinois, United States
Segal Institute for Clinical Research (Miami)
🇺🇸
North Miami, Florida, United States
Medical Research Group of Central Florida
🇺🇸
Orange City, Florida, United States