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

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

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).

Study Overview

• Status: Completed
• Conditions: Schizophrenia and Predominant Negative Symptoms
• Intervention / Treatment: Drug: SPD489 (lisdexamfetamine dimesylate); Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Lasser RA, Dirks B, Nasrallah H, Kirsch C, Gao J, Pucci ML, Knesevich MA, Lindenmayer JP. Adjunctive lisdexamfetamine dimesylate therapy in adult outpatients with predominant negative symptoms of schizophrenia: open-label and randomized-withdrawal phases. Neuropsychopharmacology. 2013 Oct;38(11):2140-9. doi: 10.1038/npp.2013.111. Epub 2013 May 8.

Helpful Links

• FDA Recall Information
• FDA-approved Label

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2009
• Primary Completion (Actual): January 20, 2011
• Study Completion (Actual): January 20, 2011

Study Registration Dates

• First Submitted: June 15, 2009
• First Submitted That Met QC Criteria: June 16, 2009
• First Posted (Estimate): June 17, 2009

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: SPD489-204