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Study to Evaluate the Efficacy and Safety of GSK239512 in Schizophrenia

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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

Brief Summary:
This study aims to evaluate the cognitive enhancing effects and tolerability of GSK239512 compared to placebo in patients with schizophrenia

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: GSK239512 Drug: Placebo Phase 2

Detailed Description:
This is a 7-week, Phase II, multi-centre, randomised, double-blind, placebo-controlled, parallel group design study in male and female subjects with schizophrenia who are stabilised on antipsychotic medication. Subjects will be randomised to receive either GSK239512 or placebo for 7 weeks. They will undergo weekly review of safety, tolerability and cognitive performance measures.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised Double-blind, Placebo Controlled, Parallel Group Study to Evaluate the Cognitive Enhancing Effect of GSK239512 in Stable Patients With Schizophrenia
Actual Study Start Date : December 1, 2009
Actual Primary Completion Date : August 10, 2011
Actual Study Completion Date : August 10, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: GSK239512
Repeat dose.
Drug: GSK239512
Histamine H3 Antagonist

Placebo Comparator: Placebo
Repeat dose. Placebo to match GSK239512
Drug: Placebo
Placebo to match GSK239512




Primary Outcome Measures :
  1. Change From Baseline in Composite Score of CSSB Following Dosing With GSK239512 [ Time Frame: Baseline and up to Week 7 ]
    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.


Secondary Outcome Measures :
  1. Change From Baseline in Composite Score of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) at Week 7 [ Time Frame: Baseline and Week 7 ]
    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.

  2. Change From Baseline in Individual Cognitive Domain Scores in CSSB at Week 7 [ Time Frame: Baseline and Week 7 ]
    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.

  3. Change From Baseline in Individual Cognitive Domain Scores in MCCB at Week 7 [ Time Frame: Baseline and Week 7 ]
    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.

  4. Change From Baseline in Brief Psychiatric Rating Scale (BPRS) at Week 7 [ Time Frame: Baseline and Week 7 ]
    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.

  5. Change From Baseline in Schedule for Assessment of Negative Symptoms (SANS) at Week 7 [ Time Frame: Baseline and Week 7 ]
    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.

  6. Change From Baseline in University of California and San Diego (UCSD) Performance Based Skills Assessment (UPSA) at Week 7 [ Time Frame: Baseline and Week 7 ]
    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

  7. Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 59 ]
    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.

  8. Number of Par. With Most Severe On-treatment Abnormal Electrocardiogram (ECG) Findings [ Time Frame: Up to Day 59 ]
    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.

  9. Number of Par. With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Readings Outside Clinical Concern Range [ Time Frame: Up to Day 59 ]
    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.

  10. Number of Par. With Heart Rate Measured Value Outside Clinical Concern Range [ Time Frame: Up to Day 59 ]
    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.

  11. Number of Par. With Abnormal Hematology Parameters Values at Any Time on Treatment [ Time Frame: Up to Day 59 ]
    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.

  12. Number of Par. With Abnormal Clinical Chemistry Parameters Values at Any Time On-treatment [ Time Frame: Up to Day 59 ]
    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.

  13. Number of Par. With Abnormal Urinalysis Parameters Values of Potential Clinical Concern [ Time Frame: Up to Day 59 ]
    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).

  14. Plasma Concentrations of GSK239512 (Cmax) at Steady State After Repeat Dosing on Dose Review Visit at Any Time On-treatment [ Time Frame: 15 minutes prior to start and 15 minutes after completion of CSSB at Week 1,2,3,4,5,6 and 7 ]
    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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Clinical diagnosis of Schizophrenia
  2. No acute exacerbation of symptoms requiring hospital admission or step up care in the previous six months.
  3. Not on any symptomatic treatment for cognition

Exclusion Criteria:

  1. Poses a significant homicidal or suicidal risk or evidence of previous homicidal or suicidal risk.
  2. Co-morbid psychiatric or significant physical illness
  3. Alcohol or drug abuse or dependence.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01009060


Locations
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United States, California
GSK Investigational Site
Garden Grove, California, United States, 92845
GSK Investigational Site
Los Angeles, California, United States, 90073
GSK Investigational Site
National City, California, United States, 91950
GSK Investigational Site
Sacramento, California, United States, 95817
GSK Investigational Site
San Diego, California, United States, 92102
GSK Investigational Site
Torrance, California, United States, 90502
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60611
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46222
United States, Maryland
GSK Investigational Site
Catonsville, Maryland, United States, 21228
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02114
GSK Investigational Site
Jamaica Plain, Massachusetts, United States, 02130
United States, New Jersey
GSK Investigational Site
Mount Laurel, New Jersey, United States, 08054
United States, New York
GSK Investigational Site
New York, New York, United States, 10016
GSK Investigational Site
New York, New York, United States, 10032
United States, North Carolina
GSK Investigational Site
Butner, North Carolina, United States, 27509
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 113147
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 113147
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 113147
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 113147
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 113147
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 113147
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 113147
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01009060     History of Changes
Other Study ID Numbers: 113147
First Posted: November 6, 2009    Key Record Dates
Results First Posted: September 27, 2017
Last Update Posted: November 8, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Keywords provided by GlaxoSmithKline:
H3 Antagonist
Schizophrenia
double blind
Histamine
randomised
placebo controlled
Cognition
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Histamine
Histamine Agonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs