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
Results First Received: December 6, 2011  
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
Condition: Schizophrenia and Predominant Negative Symptoms
Interventions: Drug: SPD489 (lisdexamfetamine dimesylate)
Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
SPD489 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, 30, 40, 50, 60 or 70 mg of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily to a stable dose of atypical antipsychotic medication. They were then randomized into the Double-Blind Phase receiving either their optimal dose of adjunctive SPD489 or placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Placebo Subjects received placebo once-daily for 4 weeks during the Double-blind Phase to a stable dose of atypical antipsychotic medication.

Participant Flow for 2 periods

Period 1:   Open-label Phase
    SPD489     Placebo  
STARTED     92     0  
COMPLETED     69     0  
NOT COMPLETED     23     0  
Adverse Event                 5                 0  
Protocol Violation                 1                 0  
Withdrawal by Subject                 11                 0  
Failure to meet randomization criteria                 1                 0  
Withdrawal criteria met                 5                 0  

Period 2:   Double-blind Phase
    SPD489     Placebo  
STARTED     34     35  
COMPLETED     27     29  
NOT COMPLETED     7     6  
Adverse Event                 1                 1  
Withdrawal by Subject                 1                 1  
Lost to Follow-up                 2                 1  
Withdrawal criteria met                 1                 1  
Noncompliance                 1                 1  
Positive urine drug screen                 1                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.

Baseline Measures
    Overall  
Number of Participants  
[units: participants]
  92  
Age  
[units: years]
Mean ± Standard Deviation
  42.3  ± 9.11  
Age, Customized  
[units: participants]
 
<18 years     0  
Between 18 and 55 years     92  
>55 years     0  
Gender  
[units: participants]
 
Female     30  
Male     62  
Region of Enrollment  
[units: participants]
 
United States     92  



  Outcome Measures
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1.  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)   [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ]

2.  Primary:   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 ]

3.  Secondary:   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 ]

4.  Secondary:   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 ]

5.  Secondary:   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 ]

6.  Secondary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   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 ]

9.  Secondary:   Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline   [ Time Frame: Open-label Baseline ]

10.  Secondary:   Percent of Participants With CGI-S at Week 10 Open-label Phase   [ Time Frame: Week 10 Open-label Phase ]

11.  Secondary:   Percent of Participants With CGI-S at Double-blind Randomization Baseline   [ Time Frame: Double-blind Randomization Baseline ]

12.  Secondary:   Percent of Participants With CGI-S at Week 4 Double-blind Phase   [ Time Frame: Week 4 Double-blind Phase ]

13.  Secondary:   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 ]

14.  Secondary:   Percent of Participants With Improvement on CGI-C at Week 4 Double-blind Phase   [ Time Frame: Double-blind Phase Week 4 ]

15.  Secondary:   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 ]

16.  Secondary:   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 ]

17.  Secondary:   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 ]

18.  Secondary:   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 ]

19.  Secondary:   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 ]

20.  Secondary:   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 ]

21.  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   [ Time Frame: Open-label Baseline and week 10 Open-label Phase ]

22.  Secondary:   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 ]

23.  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   [ Time Frame: Open-label Baseline and Week 10 Open-label Phase ]

24.  Secondary:   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 ]

25.  Secondary:   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 ]

26.  Secondary:   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 ]

27.  Secondary:   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 ]

28.  Secondary:   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 ]

29.  Secondary:   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 ]

30.  Secondary:   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 ]

31.  Secondary:   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 ]

32.  Secondary:   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 ]

33.  Secondary:   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 ]

34.  Secondary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Physician
Organization: Shire Pharmaceutical
phone: 1-866-842-5335


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