Study to Evaluate the Efficacy and Safety of GSK239512 in Schizophrenia

A Randomised Double-blind, Placebo Controlled, Parallel Group Study to Evaluate the Cognitive Enhancing Effect of GSK239512 in Stable Patients With Schizophrenia

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: GSK239512; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • 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
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46222
      • GSK Investigational Site
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • GSK Investigational Site
    • Jamaica Plain, Massachusetts, United States, 02130
      • GSK Investigational Site
  • New Jersey
    • Mount Laurel, New Jersey, United States, 08054
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10032
      • GSK Investigational Site
    • New York, New York, United States, 10016
      • GSK Investigational Site
  • North Carolina
    • Butner, North Carolina, United States, 27509
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Composite Score of CSSB Following Dosing With GSK239512	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.	Baseline and up to Week 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Composite Score of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) at 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.	Baseline and Week 7
Change From Baseline in Individual Cognitive Domain Scores in CSSB at 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.	Baseline and Week 7
Change From Baseline in Individual Cognitive Domain Scores in MCCB at 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.	Baseline and Week 7
Change From Baseline in Brief Psychiatric Rating Scale (BPRS) at 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.	Baseline and Week 7
Change From Baseline in Schedule for Assessment of Negative Symptoms (SANS) at 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.	Baseline and Week 7
Change From Baseline in University of California and San Diego (UCSD) Performance Based Skills Assessment (UPSA) at 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	Baseline and Week 7
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Up to Day 59
Number of Par. With Most Severe On-treatment Abnormal Electrocardiogram (ECG) Findings	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.	Up to Day 59
Number of Par. With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Readings Outside Clinical Concern Range	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.	Up to Day 59
Number of Par. With Heart Rate Measured Value Outside Clinical Concern Range	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.	Up to Day 59
Number of Par. With Abnormal Hematology Parameters Values at Any Time on Treatment	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.	Up to Day 59
Number of Par. With Abnormal Clinical Chemistry Parameters Values at Any Time On-treatment	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.	Up to Day 59
Number of Par. With Abnormal Urinalysis Parameters Values of Potential Clinical Concern	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).	Up to Day 59
Plasma Concentrations of GSK239512 (Cmax) at Steady State After Repeat Dosing on Dose Review Visit at Any Time On-treatment	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.	15 minutes prior to start and 15 minutes after completion of CSSB at Week 1,2,3,4,5,6 and 7

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Jarskog LF, Lowy MT, Grove RA, Keefe RS, Horrigan JP, Ball MP, Breier A, Buchanan RW, Carter CS, Csernansky JG, Goff DC, Green MF, Kantrowitz JT, Keshavan MS, Laurelle M, Lieberman JA, Marder SR, Maruff P, McMahon RP, Seidman LJ, Peykamian MA. A Phase II study of a histamine H(3) receptor antagonist GSK239512 for cognitive impairment in stable schizophrenia subjects on antipsychotic therapy. Schizophr Res. 2015 May;164(1-3):136-42. doi: 10.1016/j.schres.2015.01.041. Epub 2015 Feb 24.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2009
• Primary Completion (Actual): August 10, 2011
• Study Completion (Actual): August 10, 2011

Study Registration Dates

• First Submitted: November 5, 2009
• First Submitted That Met QC Criteria: November 5, 2009
• First Posted (Estimate): November 6, 2009

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Schizophrenia; Cognition; placebo controlled; double blind; Histamine; randomised; H3 Antagonist
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 113147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 113147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 113147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 113147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 113147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 113147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 113147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 113147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register