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Study to Evaluate the Efficacy and Safety of GSK239512 in Schizophrenia

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: NCT01009060
Recruitment Status : Completed
First Posted : November 6, 2009
Results First Posted : September 27, 2017
Last Update Posted : November 8, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: GSK239512
Drug: Placebo
Enrollment 50
Recruitment Details The study was conducted at 14 centers in the United States from 1 December 2009 to 10 August 2011. Study included d-amphetamine therapeutic challenge (dropped in amendment 2), treatment period of 7 weeks (4 weeks titration and 3 weeks of maintenance) and follow up visit approximately 7-10 days following their last dose of study medication.
Pre-assignment Details A total of 118 participants (par.) were screened. Out of these 50 participants were randomized. Out of these, safety population consisted of 50 participants and intent-to-treat (ITT) population consisted of 46 participants.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks. Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Period Title: Overall Study
Started 25 25
Completed 21 20
Not Completed 4 5
Reason Not Completed
Adverse Event             1             2
Protocol Violation             0             1
Lost to Follow-up             1             0
Physician Decision             1             1
Withdrawal by Subject             1             1
Arm/Group Title Placebo GSK239512 Total
Hide Arm/Group Description Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks. Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen. Total of all reporting groups
Overall Number of Baseline Participants 24 22 46
Hide Baseline Analysis Population Description
Baseline characteristic data is presented for ITT population which consisted of all participants randomized to treatment, who had taken at least one dose of investigational product and who had at least one post-Baseline CogState Schizophrenia Battery (CSSB) assessment during the on-treatment phase.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 22 participants 46 participants
40.1  (9.54) 38.2  (13.10) 39.2  (11.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Female
5
  20.8%
5
  22.7%
10
  21.7%
Male
19
  79.2%
17
  77.3%
36
  78.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Number
Number Analyzed 24 participants 22 participants 46 participants
African American/African Heritage 11 11 22
Native Hawaiian or other Pacific Islander 0 1 1
White - White/Caucasian/European Heritage 13 8 21
Mixed Race 0 2 2
1.Primary Outcome
Title Change From Baseline in Composite Score of CSSB Following Dosing With GSK239512
Hide Description The CSSB is a computerized battery with following domains (score range): Verbal memory (0-75), working memory (0-28), motor speed (0-100), verbal fluency, attention and speed of information processing (0-110) and executive functions with higher score representing better performance. Two Baseline CSSB testing were conducted; the first on the day prior to commencing dosing (Day -1) and the other test pre-dose on Day 1: the average of the two tests was used as Baseline. Change from Baseline was calculated as score at a given time minus score at Baseline. For each individual task from the CSSB, the Baseline was calculated as the mean of the second screening assessment and the Day 1 pre-dose assessment. A composite score was calculated by averaging all the measures, and then calculating a z-score of the composite. Higher the composite score, better is the performance. Z-score is the measure of standard deviation away from the mean score.
Time Frame Baseline and up to Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed. Par. recruited under protocol amendment 2 were not assessed at Weeks 1, 3, 5 or 6 and hence the number of par. at these visits are lower.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 24 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1 Number Analyzed 12 participants 10 participants
0.065  (0.0606) 0.016  (0.1342)
Week 2 Number Analyzed 23 participants 21 participants
0.086  (0.0814) 0.104  (0.0682)
Week 3 Number Analyzed 12 participants 9 participants
0.076  (0.0816) -0.012  (0.1139)
Week 4 Number Analyzed 22 participants 20 participants
0.157  (0.0859) 0.068  (0.0901)
Week 5 Number Analyzed 12 participants 9 participants
0.099  (0.0675) 0.184  (0.1057)
Week 6 Number Analyzed 12 participants 9 participants
-0.001  (0.1234) 0.194  (0.1539)
Week 7 Number Analyzed 22 participants 19 participants
0.004  (0.1106) 0.107  (0.1105)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments Week 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7239
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.049
Confidence Interval (2-Sided) 90%
-0.288 to 0.190
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments Week 2
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8351
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.018
Confidence Interval (2-Sided) 90%
-0.127 to 0.163
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments Week 3
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4541
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.088
Confidence Interval (2-Sided) 90%
-0.287 to 0.110
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4148
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.089
Confidence Interval (2-Sided) 90%
-0.272 to 0.093
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments Week 5
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3887
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.086
Confidence Interval (2-Sided) 90%
-0.082 to 0.254
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2594
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.195
Confidence Interval (2-Sided) 90%
-0.093 to 0.484
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments Week 7
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4778
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.103
Confidence Interval (2-Sided) 90%
-0.139 to 0.344
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Composite Score of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) at Week 7
Hide Description MCCB measures functioning across various cognitive domains and is comprised of ten tests that assess seven cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). Its measurements are based on timed paper-and-pencil, computerized, and orally-administered tests, as well as spatial tests using geometric cubes. MCCB composite T scores are between 40 and 60 (normal range) and < 40 (below normal range). Higher scores indicate better performance. The Baseline was calculated as the mean of the second screening assessment and the Day 1 pre-dose assessment. If either measurement meant to be used in the mean was missing, then the Baseline value was the non-missing assessment. If both were missing, then Baseline was considered missing and the task was excluded from the analysis. Change from Baseline was calculated as score at a given time post Baseline minus score at Baseline.
Time Frame Baseline and Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the indicated time point were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 22 19
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
1.108  (1.8759) 0.371  (1.7801)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6947
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.737
Confidence Interval (2-Sided) 90%
-3.884 to 2.409
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Individual Cognitive Domain Scores in CSSB at Week 7
Hide Description The CSSB is a computerized battery with following domains (score range): Verbal memory (0-75), working memory (0-28), motor speed (0-100), verbal fluency, attention and speed of information processing (0-110) and executive functions with higher score representing better performance. Two Baseline CSSB testing were conducted; the first on the day prior to commencing dosing (Day -1) and the other test pre-dose on Day 1: the average of the two tests was used as Baseline. Change from Baseline was calculated as score at a given time minus score at Baseline. For each individual task from the CSSB, the Baseline was calculated as the mean of the second screening assessment and the Day 1 pre-dose assessment. A composite score was calculated by averaging all the measures, and then calculating a z-score of the composite. Higher the composite score, better is the performance. Z-score is the measure of standard deviation away from the mean score.
Time Frame Baseline and Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed. Par. recruited under protocol amendment 2 were not assessed at Weeks 1, 3, 5 or 6 and hence the number of par. at these visits are lower.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 24 22
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Speed of Processing/Simple Reaction Time Number Analyzed 22 participants 18 participants
0.541  (0.1628) 0.289  (0.1391)
Attention/Vigilance Number Analyzed 22 participants 18 participants
0.067  (0.1756) 0.246  (0.1932)
Working Memory Number Analyzed 22 participants 17 participants
0.021  (0.2030) 0.412  (0.2164)
Visual Learning Number Analyzed 22 participants 19 participants
-0.198  (0.2414) 0.081  (0.1699)
Verbal Learning Number Analyzed 22 participants 19 participants
-0.558  (0.2853) -0.160  (0.2339)
Reasoning/Problem Solving Number Analyzed 22 participants 19 participants
0.016  (0.1168) 0.192  (0.1085)
Social Cognition Number Analyzed 20 participants 19 participants
-0.431  (0.1544) -0.401  (0.1339)
Working Memory (Two-Back Memory) Number Analyzed 22 participants 17 participants
0.247  (0.1862) 0.316  (0.2374)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1399
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.252
Confidence Interval (2-Sided) 90%
-0.535 to 0.030
Estimation Comments For Speed of Processing/Simple Reaction Time
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3992
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.179
Confidence Interval (2-Sided) 90%
-0.176 to 0.534
Estimation Comments For Attention/Vigilance
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1547
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.391
Confidence Interval (2-Sided) 90%
-0.063 to 0.845
Estimation Comments For Working Memory
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2531
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.279
Confidence Interval (2-Sided) 90%
-0.127 to 0.685
Estimation Comments For Visual Learning
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2417
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.398
Confidence Interval (2-Sided) 90%
-0.167 to 0.963
Estimation Comments For Verbal Learning
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2069
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.177
Confidence Interval (2-Sided) 90%
-0.055 to 0.409
Estimation Comments For Reasoning/Problem Solving
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8645
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.030
Confidence Interval (2-Sided) 90%
-0.262 to 0.322
Estimation Comments For Social Cognition
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7873
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.069
Confidence Interval (2-Sided) 90%
-0.364 to 0.503
Estimation Comments For Working Memory (Two-Back Memory)
4.Secondary Outcome
Title Change From Baseline in Individual Cognitive Domain Scores in MCCB at Week 7
Hide Description MCCB measures functioning across various cognitive domains and is comprised of ten tests that assess seven cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) Its measurements are based on timed paper-and-pencil, computerized, and orally-administered tests, as well as spatial tests using geometric cubes. MCCB composite T scores are between 40 and 60 (normal range) and < 40 (below normal range). Higher scores indicate better performance. The Baseline was calculated as the mean of the second screening assessment and the Day 1 pre-dose assessment. If either measurement meant to be used in the mean was missing, then the Baseline value was the non-missing assessment. If both were missing, then Baseline was considered missing and the task was excluded from the analysis. Change from Baseline was calculated as score at a given time post Baseline minus score at Baseline.
Time Frame Baseline and Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants at indicated time point were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 22 19
Least Squares Mean (Standard Error)
Unit of Measure: T-scores
Speed of Processing 2.045  (1.7359) -1.979  (1.6030)
Attention/Vigilance -0.111  (2.3028) -2.351  (2.1303)
Working Memory 3.368  (2.0677) 1.330  (1.9086)
Visual Learning -0.718  (2.3868) -1.464  (2.2060)
Verbal Learning -1.174  (2.1772) 1.938  (2.1123)
Reasoning and Problem Solving 0.488  (2.0863) 1.460  (1.9621)
Social Cognition -0.411  (3.0119) -0.750  (2.7790)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0225
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.024
Confidence Interval (2-Sided) 90%
-6.872 to -1.175
Estimation Comments For Speed of Processing
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3317
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.240
Confidence Interval (2-Sided) 95%
-6.085 to 1.605
Estimation Comments For Attention/Vigilance
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3243
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.038
Confidence Interval (2-Sided) 90%
-5.482 to 1.406
Estimation Comments For Working Memory
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7497
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.746
Confidence Interval (2-Sided) 90%
-4.667 to 3.175
Estimation Comments For Visual Learning
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1585
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.112
Confidence Interval (2-Sided) 90%
-0.537 to 6.761
Estimation Comments For Verbal Learning
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6582
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.972
Confidence Interval (2-Sided) 90%
-2.709 to 4.654
Estimation Comments For Reasoning and Problem Solving
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9092
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.338
Confidence Interval (2-Sided) 90%
-5.316 to 4.639
Estimation Comments For Social Cognition
5.Secondary Outcome
Title Change From Baseline in Brief Psychiatric Rating Scale (BPRS) at Week 7
Hide Description BPRS is the clinician rating of psychiatric symptoms; higher score indicates higher severity; 18-items scored 1-7; lower score is 18 and highest score is 126. The Baseline was calculated as the mean of the second screening assessment and the Day 1 pre-dose assessment. If either measurement meant to be used in the mean was missing, then the Baseline value was the non-missing assessment. If both were missing, then Baseline was considered missing and the task was excluded from the analysis. Change from Baseline was calculated as score at a given time post Baseline minus score at Baseline.
Time Frame Baseline and Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the indicated time point were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 22 20
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-2.795  (1.2410) -3.819  (1.1512)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4406
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.024
Confidence Interval (2-Sided) 90%
-3.237 to 1.190
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Schedule for Assessment of Negative Symptoms (SANS) at Week 7
Hide Description The SANS was a tool used to assess five symptom complexes to obtain clinical ratings of negative symptoms in par. with schizophrenia. Complexes include: affective blunting; alogia (impoverished thinking); avolition/apathy; anhedonia/asociality; and disturbance of attention. Assessment was conducted on six-point scale (0=not at all to 5=severe) for a total scoring range of 0-120. Lower scores represent better performance. The Baseline was calculated as the mean of the second screening assessment and the Day 1 pre-dose assessment. If either measurement meant to be used in the mean was missing, then the Baseline value was the non-missing assessment. If both were missing, then Baseline was considered missing and the task was excluded from the analysis. Change from Baseline was calculated as score at a given time post Baseline minus score at Baseline.
Time Frame Baseline and Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the indicated time point were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 22 20
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-3.206  (2.4684) -5.082  (2.4087)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5197
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.876
Confidence Interval (2-Sided) 90%
-6.743 to 2.990
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in University of California and San Diego (UCSD) Performance Based Skills Assessment (UPSA) at Week 7
Hide Description The UPSA is a measure of Functional Capacity and assesses skills involved in community tasks. It is composed of five subdomains- comprehension and planning, finance, communication, mobility and house management. When combined, measures functional capacity. The comprehension and planning ranges from 0 to 14, the finance ranges from 0 to 11, the communication ranges from 0 to 12, the mobility ranges from 0 to 9, and the house management ranges from 0 to 4. Then a medication management score of 0 to 37 is added. In total, the Assessment is thus scored on a 0 to 87 scale, with higher scores indicating better performance. The Baseline was calculated as the mean of the second screening assessment and the Day 1 pre-dose assessment. If either was missing, then the Baseline value was the non-missing assessment. If both were missing, then Baseline was considered missing and the task was excluded from the analysis. Change from Baseline was score at a given time post Baseline minus Baseline score
Time Frame Baseline and Week 7
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Hide Analysis Population Description
ITT Population. Only those participants available at the indicated time point were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 22 20
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
2.926  (2.6007) 4.750  (2.3332)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK239512
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4637
Comments [Not Specified]
Method Mixed Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.824
Confidence Interval (2-Sided) 90%
-2.334 to 5.982
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Time Frame Up to Day 59
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Hide Analysis Population Description
Safety Population consisted of all randomized par. who took at least one dose of investigational product.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 25 25
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
16
  64.0%
17
  68.0%
Any SAE
1
   4.0%
0
   0.0%
9.Secondary Outcome
Title Number of Par. With Most Severe On-treatment Abnormal Electrocardiogram (ECG) Findings
Hide Description Triplicate 12-lead ECGs were obtained at Baseline (screening visit). Single 12-lead ECGs were obtained at each subsequent time point during the study. Abnormal ECG findings were presented for the most severe on-treatment result.
Time Frame Up to Day 59
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Hide Analysis Population Description
Safety Population. Only those participants who showed most severe on-treatment abnormal ECG findings are presented.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 25 22
Measure Type: Count of Participants
Unit of Measure: Participants
8
  32.0%
10
  45.5%
10.Secondary Outcome
Title Number of Par. With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Readings Outside Clinical Concern Range
Hide Description Blood pressure readings both systolic and diastolic were collected at pre-dose and then hourly post-dose until 6 hours post-dose or until the par. got discharged. Blood pressure was measured in both standing (Std) and supine (Sup) position. Data with only abnormal values were presented. For SBP the data of concern was <90 or >140 and increase from Baseline (IFB) >=40; <90 or >140 and decrease from Baseline (DFB) >=30. For DBP the data of concern was <50 or >90 and IFB >=30; <50 or >90 and DFB >=20.
Time Frame Up to Day 59
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 25 25
Measure Type: Count of Participants
Unit of Measure: Participants
SBP, Std, Week 3, <90 or >140 and DFB>=30 Number Analyzed 23 participants 20 participants
1
   4.3%
0
   0.0%
SBP, Std, Week 4, <90 or >140 and DFB>=30 Number Analyzed 21 participants 20 participants
1
   4.8%
0
   0.0%
SBP, Std, Week 5, <90 or >140 and IFB>=40 Number Analyzed 22 participants 20 participants
1
   4.5%
0
   0.0%
SBP, Std, Week 5, <90 or >140 and DFB>=30 Number Analyzed 22 participants 20 participants
1
   4.5%
0
   0.0%
SBP, Std, Week 6, <90 or >140 and DFB>=30 Number Analyzed 22 participants 20 participants
1
   4.5%
0
   0.0%
SBP, Std, follow-up, <90 or >140 and DFB>=30 Number Analyzed 23 participants 24 participants
1
   4.3%
0
   0.0%
SBP, Sup, Week 5, <90 or >140 and IFB>=40 Number Analyzed 22 participants 20 participants
1
   4.5%
0
   0.0%
DBP, Std, Week 6, <50 or >90 and IBP >=30 Number Analyzed 22 participants 20 participants
1
   4.5%
0
   0.0%
DBP, Sup, Week 6, <50 or >90 and IBP >=30 Number Analyzed 22 participants 20 participants
1
   4.5%
0
   0.0%
11.Secondary Outcome
Title Number of Par. With Heart Rate Measured Value Outside Clinical Concern Range
Hide Description Heart rate readings were collected at pre-dose and then hourly post-dose until 6 hours post-dose or until the participant got discharged. It was measured in both supine and standing position. For both Std and Sup positions, heart rate data of concern was <50 or >100 and IFB >=30; <50 or >100 and DFB >=30. Data with only abnormal values were presented.
Time Frame Up to Day 59
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 25 25
Measure Type: Count of Participants
Unit of Measure: Participants
Std, Week 5, <50 or >100 and IFB >=30 Number Analyzed 22 participants 20 participants
1
   4.5%
0
   0.0%
Std, follow-up, <50 or >100 and IFB >=30 Number Analyzed 23 participants 24 participants
1
   4.3%
0
   0.0%
12.Secondary Outcome
Title Number of Par. With Abnormal Hematology Parameters Values at Any Time on Treatment
Hide Description Hematology parameters: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, Mean Corpuscle Hemoglobin (MCH), Mean Corpuscle Hemoglobin concentration (MCHC), Mean Corpuscle Volume (MCV), Monocytes, Platelet count, Red blood cell count (RBC), Reticulocytes, Neutrophils count and White blood cell (WBC) count were presented as values of potential clinical concern at any time on treatment. Only those parameters with any abnormal value are presented.
Time Frame Up to Day 59
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the indicated time point were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 25 22
Measure Type: Count of Participants
Unit of Measure: Participants
Eosinophils, Low
8
  32.0%
4
  18.2%
Eosinophils, High
1
   4.0%
0
   0.0%
Hemoglobin, Low
1
   4.0%
0
   0.0%
Monocytes, Low
3
  12.0%
1
   4.5%
RBC count, Low
1
   4.0%
0
   0.0%
Reticulocytes, Low
1
   4.0%
1
   4.5%
Neutrophils count, Low
1
   4.0%
0
   0.0%
13.Secondary Outcome
Title Number of Par. With Abnormal Clinical Chemistry Parameters Values at Any Time On-treatment
Hide Description Clinical chemistry parameters: Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Amino Transferase (AST), Calcium, Creatinine, Direct Bilirubin, Gamma Glutamyl Transferase (GGT), Glucose, Potassium, Sodium, Total Bilirubin, Total protein, Urea/ Blood urea nitrogen (BUN) were presented as values of potential clinical concern at any time on treatment. Only those parameters with any abnormal value are presented.
Time Frame Up to Day 59
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the indicated time point were analyzed.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 25 22
Measure Type: Count of Participants
Unit of Measure: Participants
ALT, High
1
   4.0%
3
  13.6%
AST, High
1
   4.0%
1
   4.5%
GGT, High
0
   0.0%
3
  13.6%
Glucose, Low
2
   8.0%
3
  13.6%
Glucose, High
5
  20.0%
4
  18.2%
14.Secondary Outcome
Title Number of Par. With Abnormal Urinalysis Parameters Values of Potential Clinical Concern
Hide Description Samples for urinalysis were collected on Days 1, 7, 14, 21, 28, 35, 42, 49 and up to Day 59 (follow-up) to assess specific gravity, pH, glucose, protein, blood and ketone by dipstick and microscopic examination (if blood or protein is abnormal).
Time Frame Up to Day 59
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population.
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description:
Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks.
Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 micrograms (μg) GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
Overall Number of Participants Analyzed 25 25
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Plasma Concentrations of GSK239512 (Cmax) at Steady State After Repeat Dosing on Dose Review Visit at Any Time On-treatment
Hide Description One Pharmacokinetic (PK) sample was collected within 15 minutes prior to the start of the CSSB and one PK sample was collected within 15 minutes after completion of the CSSB. ‘n’ was the number of samples available for analysis.
Time Frame 15 minutes prior to start and 15 minutes after completion of CSSB at Week 1,2,3,4,5,6 and 7
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Hide Analysis Population Description
PK-concentration population included all par. for whom a PK sample was obtained and analyzed. Number of units analyzed are number of samples available for analysis.
Arm/Group Title GSK239512 10 mcg GSK239512 20 mcg GSK239512 40 mcg GSK239512 80 mcg
Hide Arm/Group Description:
Par. received GSK239512 10 mcg daily as dose level 1 in the first week of study.
Par. received GSK239512 20 mcg daily as dose level 2 in the second week of study.
Par. received GSK239512 40 mcg daily as dose level 3 in the third week of study.
Par. received GSK239512 80 mcg daily as dose level 4 in the fourth week of study and continued to receive from fifth to seventh week as maintenance phase.
Overall Number of Participants Analyzed 21 21 21 21
Overall Number of Units Analyzed
Type of Units Analyzed: Plasma sample
13 30 11 41
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
0.0250
(37.44%)
0.0496
(29.84%)
0.0790
(51.85%)
0.1775
(42.91%)
Time Frame All SAEs and non-SAEs were reported up to Day 59.
Adverse Event Reporting Description Safety Population were used to report the AEs and serious AEs.
 
Arm/Group Title Placebo GSK239512
Hide Arm/Group Description Par. received oral placebo tablet matching with GSK239512 once daily for a period of 7 weeks. Par. received oral GSK239512 once daily for a period of 7 weeks (4 weeks titration and 3 weeks at maintenance). Par. started at a daily dose of 10 μg GSK239512 and titrated up weekly through successive dose levels of 20 μg, 40 μg up to a maximum dose of 80 μg according to the titration regimen.
All-Cause Mortality
Placebo GSK239512
Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/25 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo GSK239512
Affected / at Risk (%) Affected / at Risk (%)
Total   1/25 (4.00%)   0/25 (0.00%) 
Psychiatric disorders     
Stress  1  1/25 (4.00%)  0/25 (0.00%) 
1
Term from vocabulary, MedDRA 14.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo GSK239512
Affected / at Risk (%) Affected / at Risk (%)
Total   11/25 (44.00%)   15/25 (60.00%) 
Gastrointestinal disorders     
Diarrhoea  1  1/25 (4.00%)  2/25 (8.00%) 
Nausea  1  3/25 (12.00%)  0/25 (0.00%) 
General disorders     
Fatigue  1  3/25 (12.00%)  1/25 (4.00%) 
Nervous system disorders     
Headache  1  4/25 (16.00%)  6/25 (24.00%) 
Somnolence  1  1/25 (4.00%)  3/25 (12.00%) 
Dizziness  1  0/25 (0.00%)  2/25 (8.00%) 
Psychiatric disorders     
Middle insomnia  1  2/25 (8.00%)  3/25 (12.00%) 
Abnormal dreams  1  2/25 (8.00%)  2/25 (8.00%) 
Insomnia  1  1/25 (4.00%)  2/25 (8.00%) 
Nightmare  1  1/25 (4.00%)  2/25 (8.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  2/25 (8.00%)  0/25 (0.00%) 
1
Term from vocabulary, MedDRA 14.0
Indicates events were collected by systematic assessment
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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01009060     History of Changes
Other Study ID Numbers: 113147
First Submitted: November 5, 2009
First Posted: November 6, 2009
Results First Submitted: July 5, 2017
Results First Posted: September 27, 2017
Last Update Posted: November 8, 2017