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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00922272
First received: June 15, 2009
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

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).


Condition Intervention Phase
Schizophrenia and Predominant Negative Symptoms
Drug: SPD489 (lisdexamfetamine dimesylate)
Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • 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) [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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) [ Time Frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: No ]
    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:
  • Percent of Participants In Open-label Phase Who Were SANS-18 Responders at Week 10 Open-label Phase [ Time Frame: Week 10 Open-label Phase ] [ Designated as safety issue: No ]

    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 In Double-blind Phase Who Maintained SANS-18 Response at Week 4 Double-blind Phase [ Time Frame: Week 4 Double-blind Phase ] [ Designated as safety issue: No ]

    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 [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Randomization Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4 Double-blind Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Phase Week 10 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Phase Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Baseline and week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Randomization Baseline and Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Baseline and week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Randomization Baseline and Week 4 ] [ Designated as safety issue: No ]
    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 Hopkins Verbal Learning Test - Revised (HVLT-R) Total Score at Week 10 Open-label Phase [ Time Frame: Open-label Baseline and Week 10 ] [ Designated as safety issue: No ]
    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 HVLT-R Total Scores at Week 4 Double-blind Phase [ Time Frame: Double-blind Randomization Baseline and week 4 Double-blind Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Baseline and week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: No ]
    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 [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and week 10 Open-label Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: Yes ]
    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 Double-blind Randomization Baseline in ACSA Total Score at Week 4 Double-blind Phase [ Time Frame: Double-blind Randomization Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and Week 4 Double-blind Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Open-label Baseline and Week 4 of Double-blind Phase ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 92
Study Start Date: September 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SPD489 (Lisdexamfetamine dimesylate) Drug: SPD489 (lisdexamfetamine dimesylate)
oral, 20, 30, 40, 50, 60, or 70 mg once daily
Other Name: Vyvanse
Placebo Comparator: Placebo
Placebo
Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)
oral, once daily

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00922272

Locations
United States, Arkansas
K&S Professional Research Services
Little Rock, Arkansas, United States, 72201
United States, California
South Coast Clinical Trials
Anaheim, California, United States, 92804
Omega Clinical Trials
Anaheim, California, United States, 92805
Clinical Innovations
Costa Mesa, California, United States, 92626
Collaborative Neuroscience Network, Inc.
Garden Grove, California, United States, 92845
Apostle Clinical Trials, Inc.
Long Beach, California, United States, 90813
Excell Research, Inc.
Oceanside, California, United States, 92056
Southcoast Clinical Trials
San Bernardino, California, United States, 92405
Affiliated Research Institute
San Diego, California, United States, 92108
Artemis Institute for Clinical Research
San Diego, California, United States, 92123
CNRI San Diego & Los Angeles
San Diego, California, United States, 92102
Neuropsychiatric Research Center of Orange County
Santa Ana, California, United States, 92701
United States, Florida
Accurate Clinical Trials
Kissimmee, Florida, United States, 34741
Behavioral Clinical Research, INC
Lauderhill, Florida, United States, 33319
Segal Institute for Clinical Research (Miami)
North Miami, Florida, United States, 33161
Medical Research Group of Central Florida
Orange City, Florida, United States, 32763
Stedman Clinical Trials
Tampa, Florida, United States, 33613
United States, Georgia
Comprehensive NeuroScience
Atlanta, Georgia, United States, 30328
United States, Illinois
Uptown Research Institute
Chicago, Illinois, United States, 60640
United States, Louisiana
J. Gary Booker, MD, APMC
Shreveport, Louisiana, United States, 71104
United States, New Jersey
CRI Worldwide, LLC.
Willingboro, New Jersey, United States, 08046
United States, New York
Advanced Bio-Behavioral Sciences
Elmsford, New York, United States, 10523
Comprehensive Neuroscience, Inc.
Holliswood, New York, United States, 11423
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
CRI Worldwide
Philadelphia, Pennsylvania, United States, 19139
United States, Texas
Community Clinical Research, Inc.
Austin, Texas, United States, 78756
University Hills Clinical Research
Irving, Texas, United States, 75062
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Jean Pierre Lindenmayer, MD NY University School of Medicine Manhattan Psych Center
  More Information

Additional Information:
No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00922272     History of Changes
Other Study ID Numbers: SPD489-204
Study First Received: June 15, 2009
Results First Received: December 6, 2011
Last Updated: June 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Dextroamphetamine
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014