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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00922272
Recruitment Status : Completed
First Posted : June 17, 2009
Results First Posted : February 20, 2012
Last Update Posted : March 23, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia and Predominant Negative Symptoms
Interventions Drug: SPD489 (lisdexamfetamine dimesylate)
Drug: Placebo matching SPD489 (lisdexamfetamine dimesylate)
Enrollment 92
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title SPD489 Placebo
Hide Arm/Group Description 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. Subjects received placebo once-daily for 4 weeks during the Double-blind Phase to a stable dose of atypical antipsychotic medication.
Period Title: Open-label Phase
Started 92 0
Completed 69 0
Not Completed 23 0
Reason Not Completed
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 Title: Double-blind Phase
Started 34 35
Completed 27 29
Not Completed 7 6
Reason Not Completed
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
Arm/Group Title Overall
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 92
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants
42.3  (9.11)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 92 participants
<18 years 0
Between 18 and 55 years 92
>55 years 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants
Female
30
  32.6%
Male
62
  67.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 92 participants
92
1.Primary Outcome
Title 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)
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Open-label Phase Full Analysis Set (FAS) defined as all enrolled subjects who took at least 1 dose of the investigational product and had 1 primary efficacy assessment after baseline in the Open-label Phase.
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 92
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-12.9  (10.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Change From Double-blind Randomization Baseline in SANS-18 Total Score at Week 4 Double-blind Phase, Termination Observation Carried Forward (TOCF)
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Evaluable Set (RES) defined as all randomized subjects who were responders (Response is defined as reduction in total SANS score of greater than or equal to 20%) at the Double-blind Randomization and had SANS-18 total scores at week 4 of the Double-blind Phase or the early termination visit.
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 15 20
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
4.5  (2.14) 2.2  (1.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4182
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-3.4 to 8.1
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent of Participants In Open-label Phase Who Were SANS-18 Responders at Week 10 Open-label Phase
Hide Description

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.

Time Frame Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: Percent of participants
52.9
4.Secondary Outcome
Title Percent of Participants In Double-blind Phase Who Maintained SANS-18 Response at Week 4 Double-blind Phase
Hide Description

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.

Time Frame Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
RES
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 14 17
Measure Type: Number
Unit of Measure: Percent of participants
71.4 82.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6705
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Change From Open-label Baseline in SANS Global Scores at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Affective Flattening -0.9  (0.80)
Alogia -0.9  (0.65)
Avolition-Apathy -0.5  (0.81)
Anhedonia-Asociality -0.7  (0.77)
Attention -0.7  (0.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Affective Flattening
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Alogia
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Avolition-Apathy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Anhedonia-Asociality
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Attention
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Change From Double-blind Randomization Baseline in SANS Global Scores at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
RES
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 14 17
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Affective Flattening 0.2  (0.17) 0.2  (0.15)
Alogia 0.5  (0.21) 0.0  (0.19)
Avolition-Apathy 0.2  (0.16) 0.1  (0.15)
Anhedonia-Asociality 0.3  (0.18) 0.1  (0.16)
Attention 0.4  (0.18) 0.3  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Affective Flattening
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8771
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.4 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Alogia
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0584
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
0.0 to 1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Avolition-Apathy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5215
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Anhedonia-Asociality
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4835
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.3 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Attention
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5723
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.7
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Open-label Baseline in Positive and Negative Syndrome Scale (PANSS) Scores at Week 10 Open-label Phase, LOCF
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 92
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Positive subscale -1.0  (2.23)
Negative subscale -4.8  (4.01)
General Psychopathology subscale -4.0  (5.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Positive subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Negative subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments General Psychopathology subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Change From Double-blind Randomization Baseline in PANSS Scores at Week 4 Double-blind Phase, TOCF
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS defined as all subjects who received randomized investigational product and had a SANS-18 total scores at week 4 or at the early termination visit.
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 34 35
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Positive subscale 0.5  (0.31) -0.1  (0.31)
Negative subscale 0.9  (0.46) -0.1  (0.45)
General Psychopathology subscale 0.9  (0.78) -0.9  (0.77)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Positive subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1975
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.3 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Negative subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1228
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-0.3 to 2.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments General Psychopathology subscale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1115
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-0.4 to 3.9
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline
Hide Description 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)
Time Frame Open-label Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 92
Measure Type: Number
Unit of Measure: Percent of participants
Normal, not at all ill 0
Borderline mentally ill 0
Mildly ill 29.3
Moderately ill 55.4
Markedly ill 14.1
Severely ill 1.1
Among the most extremely ill 0
10.Secondary Outcome
Title Percent of Participants With CGI-S at Week 10 Open-label Phase
Hide Description 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)
Time Frame Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: Percent of participants
Normal, not at all ill 0
Borderline mentally ill 2.9
Mildly ill 54.3
Moderately ill 38.6
Markedly ill 4.3
Severely ill 0
Among the most extremely ill 0
11.Secondary Outcome
Title Percent of Participants With CGI-S at Double-blind Randomization Baseline
Hide Description 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)
Time Frame Double-blind Randomization Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 34 35
Measure Type: Number
Unit of Measure: Percent of participants
Normal, not at all ill 0 0
Borderline mentally ill 2.9 2.9
Mildly ill 50.0 60.0
Moderately ill 38.2 37.1
Markedly ill 8.8 0
Severely ill 0 0
Among the most extremely ill 0 0
12.Secondary Outcome
Title Percent of Participants With CGI-S at Week 4 Double-blind Phase
Hide Description 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)
Time Frame Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 29 29
Measure Type: Number
Unit of Measure: Percent of participants
Normal, not at all ill 0 0
Borderline mentally ill 3.4 13.8
Mildly ill 34.5 69.0
Moderately ill 48.3 13.8
Markedly ill 13.8 3.4
Severely ill 0 0
Among the most extremely ill 0 0
13.Secondary Outcome
Title Percent of Participants With Improvement on Clinical Global Impression - Change (CGI-C) at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Phase Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: Percent of participants
30.0
14.Secondary Outcome
Title Percent of Participants With Improvement on CGI-C at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Phase Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 29 29
Measure Type: Number
Unit of Measure: Percent of participants
17.2 27.6
15.Secondary Outcome
Title Change From Open-label Baseline in the Brief Assessment of Cognition in Schizophrenia (BACS) Total Score at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 73
Mean (Standard Deviation)
Unit of Measure: correct numerals
2.3  (8.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0307
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
16.Secondary Outcome
Title Change From Double-blind Randomization Baseline in BACS Total Score at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 32 31
Least Squares Mean (Standard Error)
Unit of Measure: correct numerals
0.1  (1.19) -2.7  (1.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1072
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-0.6 to 6.2
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change From Open-label Baseline in Letter-Number Span Test (LNS) Total Score at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 73
Mean (Standard Deviation)
Unit of Measure: correct sequences
0.8  (7.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3660
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
18.Secondary Outcome
Title Change From Double-blind Randomization Baseline in LNS Total Score at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 32 31
Least Squares Mean (Standard Error)
Unit of Measure: correct sequences
-0.1  (1.26) 1.3  (1.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4347
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-5.0 to 2.2
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Open-label Baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) Total Score at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 73
Mean (Standard Deviation)
Unit of Measure: words recalled
0.7  (7.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4312
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
20.Secondary Outcome
Title Change From Double-blind Randomization Baseline in HVLT-R Total Scores at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Randomization Baseline and week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 31 31
Least Squares Mean (Standard Error)
Unit of Measure: words recalled
-1.5  (1.01) 1.0  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0874
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-5.4 to 0.4
Estimation Comments [Not Specified]
21.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Open-label Baseline and week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 83
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Total Skills 6.2  (12.20)
Communication Skills 3.7  (8.56)
Financial Skills 2.5  (7.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Total Skills
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Communication Skills
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Financial Skills
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
22.Secondary Outcome
Title Change From Double-blind Randomization Baseline in UPSA-B Scores at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 32 31
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Total Skills -1.5  (1.35) 0.0  (1.37)
Communication Skills -1.5  (1.14) -0.6  (1.16)
Financial Skills -0.3  (0.83) 0.9  (0.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Total Skills
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4637
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-5.3 to 2.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Communication Skills
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6137
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-4.1 to 2.4
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase), Placebo (Double-blind Phase)
Comments Financial Skills
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3482
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-3.5 to 1.3
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Open-label Baseline in Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) T-scores at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Mean (Standard Deviation)
Unit of Measure: T-scores
Global Executive Composite -3.9  (13.29)
Behavioral Recognition Index -3.1  (12.89)
Metacognition Index -3.9  (13.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Global Executive Composite
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0174
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Behavioral Recognition Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0461
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Open-label Phase)
Comments Metacognition Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0146
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
24.Secondary Outcome
Title Change From Double-blind Randomization Baseline in BRIEF-A T-Scores at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized FAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 29 33
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
Global Executive Composite -1.7  (1.19) -1.2  (1.12)
Behavioral Recognition Index -0.9  (1.22) -1.6  (1.14)
Metacognition Index -2.0  (1.26) -0.7  (1.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase)
Comments Global Executive Composite
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7418
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-3.8 to 2.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase)
Comments Behavioral Recognition Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6429
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-2.6 to 4.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection SPD489 (Double-blind Phase)
Comments Metacognition Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4364
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-4.8 to 2.1
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Change From Open-label Baseline in Simpson Angus Scale (SAS) Total Score at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
SAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.01  (0.063)
26.Secondary Outcome
Title Change From Open-label Baseline in SAS Total Score at Week 4 of Double-blind Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized SAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 32 33
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.00  (0.093) 0.00  (0.043)
27.Secondary Outcome
Title Change From Open-label Baseline in Barnes Akathisia Scale (BAS) Scores at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
SAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Objective 0.0  (0.17)
Subjective 0.0  (0.56)
Global 0.0  (0.36)
28.Secondary Outcome
Title Change From Open-label Baseline in BAS Scores at Week 4 of Double-blind Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized SAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 32 33
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Objective 0.0  (0.18) -0.1  (0.24)
Subjective 0.0  (0.31) -0.1  (0.65)
Global 0.0  (0.18) -0.2  (0.44)
29.Secondary Outcome
Title Change From Open-label Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
SAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 85
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-1.8  (9.69)
30.Secondary Outcome
Title Change From Double-blind Randomization Baseline in ACSA Total Score at Week 4 Double-blind Phase
Hide Description 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.
Time Frame Double-blind Randomization Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized SAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 29 29
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.4  (7.65) -2.9  (8.75)
31.Secondary Outcome
Title Change From Open-label Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Global Score at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
SAS
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 69
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.7  (3.15)
32.Secondary Outcome
Title Change From Open-label Baseline in PSQI Total Global Score at Week 4 of Double-blind Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 4 Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized SAS
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 32 32
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.3  (3.01) -1.7  (3.00)
33.Secondary Outcome
Title Change From Open-label Baseline in Calgary Depression Scale for Schizophrenia (CDSS) at Week 10 Open-label Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 10 Open-label Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAS) 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.
Arm/Group Title SPD489 (Open-label Phase)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 70
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.7  (2.11)
34.Secondary Outcome
Title Change From Open-label Baseline in CDSS at Week 4 of Double-blind Phase
Hide Description 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.
Time Frame Open-label Baseline and Week 4 of Double-blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized SAS defined as all subjects who took at least 1 dose of randomized investigational product and for whom at least 1 follow-up safety assessment was made.
Arm/Group Title SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description:
Subjects receive optimal dose (20, 30, 40, 50, 60 or 70 mg) of adjunctive SPD489 (Lisdexamfetamine dimesylate) once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Subjects receive placebo once-daily for 4 weeks to a stable dose of atypical antipsychotic medication.
Overall Number of Participants Analyzed 32 33
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.1  (2.34) -0.7  (2.30)
Time Frame [Not Specified]
Adverse Event Reporting Description Safety Analysis Set for both the Open-label and Double-blind Randomization Phases.
 
Arm/Group Title SPD489 (Open-label Phase) SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Hide Arm/Group Description Subjects receive either 20, 30, 40, 50, 60 or 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily Subjects receive either 20, 30, 40, 50, 60 or 70 mg of SPD489 (Lisdexamfetamine dimesylate) once-daily Subjects receive placebo once-daily
All-Cause Mortality
SPD489 (Open-label Phase) SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
SPD489 (Open-label Phase) SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/92 (3.26%)   1/34 (2.94%)   2/35 (5.71%) 
Gastrointestinal disorders       
Dyspepsia  0/92 (0.00%)  0/34 (0.00%)  1/35 (2.86%) 
General disorders       
Chest pain  1/92 (1.09%)  0/34 (0.00%)  0/35 (0.00%) 
Psychiatric disorders       
Schizophrenia  1/92 (1.09%)  1/34 (2.94%)  1/35 (2.86%) 
Hallucination  1/92 (1.09%)  0/34 (0.00%)  0/35 (0.00%) 
Major depression  1/92 (1.09%)  0/34 (0.00%)  0/35 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
SPD489 (Open-label Phase) SPD489 (Double-blind Phase) Placebo (Double-blind Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   56/92 (60.87%)   11/34 (32.35%)   7/35 (20.00%) 
Gastrointestinal disorders       
Diarrhea  5/92 (5.43%)  0/34 (0.00%)  0/35 (0.00%) 
Dry Mouth  6/92 (6.52%)  1/34 (2.94%)  0/35 (0.00%) 
Nausea  2/92 (2.17%)  2/34 (5.88%)  1/35 (2.86%) 
Abdominal distention  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Abdominal pain upper  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Dyspepsia  3/92 (3.26%)  0/34 (0.00%)  1/35 (2.86%) 
Vomiting  4/92 (4.35%)  0/34 (0.00%)  0/35 (0.00%) 
Stomach discomfort  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
General disorders       
Fatigue  4/92 (4.35%)  2/34 (5.88%)  1/35 (2.86%) 
Nasopharyngitis  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Hernia  0/92 (0.00%)  0/34 (0.00%)  1/35 (2.86%) 
Irritability  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Infections and infestations       
Influenza  0/92 (0.00%)  0/34 (0.00%)  1/35 (2.86%) 
Injury, poisoning and procedural complications       
Skin laceration  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Animal bite  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Investigations       
Weight decreased  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Weight increased  3/92 (3.26%)  0/34 (0.00%)  0/35 (0.00%) 
Blood pressure diastolic increased  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Blood prolactin increased  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Electrocardiogram T wave abnormal  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Metabolism and nutrition disorders       
Decreased Appetite  10/92 (10.87%)  0/34 (0.00%)  0/35 (0.00%) 
Anorexia  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Increased appetite  3/92 (3.26%)  0/34 (0.00%)  0/35 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Pain in extremity  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Nervous system disorders       
Dizziness  8/92 (8.70%)  0/34 (0.00%)  0/35 (0.00%) 
Headache  13/92 (14.13%)  2/34 (5.88%)  2/35 (5.71%) 
Sedation  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
Somnolence  3/92 (3.26%)  0/34 (0.00%)  1/35 (2.86%) 
Aphasia  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Migraine  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Psychiatric disorders       
Insomnia  10/92 (10.87%)  0/34 (0.00%)  0/35 (0.00%) 
Agitation  3/92 (3.26%)  1/34 (2.94%)  0/35 (0.00%) 
Anxiety  4/92 (4.35%)  1/34 (2.94%)  0/35 (0.00%) 
Depressed mood  4/92 (4.35%)  0/34 (0.00%)  0/35 (0.00%) 
Restlessness  0/92 (0.00%)  1/34 (2.94%)  0/35 (0.00%) 
Schizophrenia  0/92 (0.00%)  1/34 (2.94%)  1/35 (2.86%) 
Reproductive system and breast disorders       
Menstruation irregular  0/92 (0.00%)  0/34 (0.00%)  1/35 (2.86%) 
Respiratory, thoracic and mediastinal disorders       
Cough  4/92 (4.35%)  0/34 (0.00%)  0/35 (0.00%) 
Rhinorrhea  4/92 (4.35%)  0/34 (0.00%)  0/35 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash erythematous  2/92 (2.17%)  0/34 (0.00%)  0/35 (0.00%) 
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.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Physician
Organization: Shire Pharmaceutical
Phone: 1-866-842-5335
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00922272     History of Changes
Other Study ID Numbers: SPD489-204
First Submitted: June 15, 2009
First Posted: June 17, 2009
Results First Submitted: December 6, 2011
Results First Posted: February 20, 2012
Last Update Posted: March 23, 2015