NCT01009060

Study to Evaluate the Efficacy and Safety of GSK239512 in Schizophrenia

Completed Phase 2 Results posted Last updated 8 November 2017

What this trial tests

Phase 2 trial testing GSK239512 in Schizophrenia in 50 participants. Completed in 10 August 2011.

Timeline

1 December 2009

Primary endpoint
10 August 2011

10 August 2011

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	50
Start date	1 December 2009
Primary completion	10 August 2011
Estimated completion	10 August 2011
Sites	15 locations across United States

Drugs / interventions tested

• GSK239512 — full drug profile →
• Placebo

Conditions studied

• Schizophrenia — all drugs for Schizophrenia →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 55, any sex, with Schizophrenia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Composite Score of CSSB Following Dosing With GSK239512 Primary · 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, th

Week 1

Group	Value	95% CI
Placebo	0.065	± 0.0606
GSK239512	0.016	± 0.1342

Week 2

Group	Value	95% CI
Placebo	0.086	± 0.0814
GSK239512	0.104	± 0.0682

Week 3

Group	Value	95% CI
Placebo	0.076	± 0.0816
GSK239512	-0.012	± 0.1139

Week 4

Group	Value	95% CI
Placebo	0.157	± 0.0859
GSK239512	0.068	± 0.0901

Week 5

Group	Value	95% CI
Placebo	0.099	± 0.0675
GSK239512	0.184	± 0.1057

Week 6

Group	Value	95% CI
Placebo	-0.001	± 0.1234
GSK239512	0.194	± 0.1539

Week 7

Group	Value	95% CI
Placebo	0.004	± 0.1106
GSK239512	0.107	± 0.1105

Change From Baseline in Composite Score of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) at Week 7 Secondary · 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 th

Group	Value	95% CI
Placebo	1.108	± 1.8759
GSK239512	0.371	± 1.7801

Change From Baseline in Individual Cognitive Domain Scores in CSSB at Week 7 Secondary · 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, th

Speed of Processing/Simple Reaction Time

Group	Value	95% CI
Placebo	0.541	± 0.1628
GSK239512	0.289	± 0.1391

Attention/Vigilance

Group	Value	95% CI
Placebo	0.067	± 0.1756
GSK239512	0.246	± 0.1932

Working Memory

Group	Value	95% CI
Placebo	0.021	± 0.2030
GSK239512	0.412	± 0.2164

Visual Learning

Group	Value	95% CI
Placebo	-0.198	± 0.2414
GSK239512	0.081	± 0.1699

Verbal Learning

Group	Value	95% CI
Placebo	-0.558	± 0.2853
GSK239512	-0.160	± 0.2339

Reasoning/Problem Solving

Group	Value	95% CI
Placebo	0.016	± 0.1168
GSK239512	0.192	± 0.1085

Social Cognition

Group	Value	95% CI
Placebo	-0.431	± 0.1544
GSK239512	-0.401	± 0.1339

Working Memory (Two-Back Memory)

Group	Value	95% CI
Placebo	0.247	± 0.1862
GSK239512	0.316	± 0.2374

Change From Baseline in Individual Cognitive Domain Scores in MCCB at Week 7 Secondary · 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

Speed of Processing

Group	Value	95% CI
Placebo	2.045	± 1.7359
GSK239512	-1.979	± 1.6030

Attention/Vigilance

Group	Value	95% CI
Placebo	-0.111	± 2.3028
GSK239512	-2.351	± 2.1303

Working Memory

Group	Value	95% CI
Placebo	3.368	± 2.0677
GSK239512	1.330	± 1.9086

Visual Learning

Group	Value	95% CI
Placebo	-0.718	± 2.3868
GSK239512	-1.464	± 2.2060

Verbal Learning

Group	Value	95% CI
Placebo	-1.174	± 2.1772
GSK239512	1.938	± 2.1123

Reasoning and Problem Solving

Group	Value	95% CI
Placebo	0.488	± 2.0863
GSK239512	1.460	± 1.9621

Social Cognition

Group	Value	95% CI
Placebo	-0.411	± 3.0119
GSK239512	-0.750	± 2.7790

Change From Baseline in Brief Psychiatric Rating Scale (BPRS) at Week 7 Secondary · 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.

Group	Value	95% CI
Placebo	-2.795	± 1.2410
GSK239512	-3.819	± 1.1512

Change From Baseline in Schedule for Assessment of Negative Symptoms (SANS) at Week 7 Secondary · 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, t

Group	Value	95% CI
Placebo	-3.206	± 2.4684
GSK239512	-5.082	± 2.4087

Change From Baseline in University of California and San Diego (UCSD) Performance Based Skills Assessment (UPSA) at Week 7 Secondary · 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 indica

Group	Value	95% CI
Placebo	2.926	± 2.6007
GSK239512	4.750	± 2.3332

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · 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.

Any AE

Group	Value	95% CI
Placebo	16
GSK239512	17

Any SAE

Group	Value	95% CI
Placebo	1
GSK239512	0

Number of Par. With Most Severe On-treatment Abnormal Electrocardiogram (ECG) Findings Secondary · 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.

Group	Value	95% CI
Placebo	8
GSK239512	10

Number of Par. With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Readings Outside Clinical Concern Range Secondary · 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.

SBP, Std, Week 3, <90 or >140 and DFB>=30

Group	Value	95% CI
Placebo	1
GSK239512	0

SBP, Std, Week 4, <90 or >140 and DFB>=30

Group	Value	95% CI
Placebo	1
GSK239512	0

SBP, Std, Week 5, <90 or >140 and IFB>=40

Group	Value	95% CI
Placebo	1
GSK239512	0

SBP, Std, Week 5, <90 or >140 and DFB>=30

Group	Value	95% CI
Placebo	1
GSK239512	0

SBP, Std, Week 6, <90 or >140 and DFB>=30

Group	Value	95% CI
Placebo	1
GSK239512	0

SBP, Std, follow-up, <90 or >140 and DFB>=30

Group	Value	95% CI
Placebo	1
GSK239512	0

SBP, Sup, Week 5, <90 or >140 and IFB>=40

Group	Value	95% CI
Placebo	1
GSK239512	0

DBP, Std, Week 6, <50 or >90 and IBP >=30

Group	Value	95% CI
Placebo	1
GSK239512	0

Number of Par. With Heart Rate Measured Value Outside Clinical Concern Range Secondary · 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.

Std, Week 5, <50 or >100 and IFB >=30

Group	Value	95% CI
Placebo	1
GSK239512	0

Std, follow-up, <50 or >100 and IFB >=30

Group	Value	95% CI
Placebo	1
GSK239512	0

Number of Par. With Abnormal Hematology Parameters Values at Any Time on Treatment Secondary · 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.

Eosinophils, Low

Group	Value	95% CI
Placebo	8
GSK239512	4

Eosinophils, High

Group	Value	95% CI
Placebo	1
GSK239512	0

Hemoglobin, Low

Group	Value	95% CI
Placebo	1
GSK239512	0

Monocytes, Low

Group	Value	95% CI
Placebo	3
GSK239512	1

RBC count, Low

Group	Value	95% CI
Placebo	1
GSK239512	0

Reticulocytes, Low

Group	Value	95% CI
Placebo	1
GSK239512	1

Neutrophils count, Low

Group	Value	95% CI
Placebo	1
GSK239512	0

Adverse events — posted to ClinicalTrials.gov

Time frame: All SAEs and non-SAEs were reported up to Day 59.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/25 (4%)

Deaths: 0/25

GSK239512

Serious: 0/25 (0%)

Deaths: 0/25

Serious adverse events (1 terms)

Reaction	System	Placebo	GSK239512
Stress	Psychiatric disorders	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	Placebo	GSK239512
Headache	Nervous system disorders	—	—
Somnolence	Nervous system disorders	—	—
Middle insomnia	Psychiatric disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Dizziness	Nervous system disorders	—	—
Abnormal dreams	Psychiatric disorders	—	—
Insomnia	Psychiatric disorders	—	—
Nightmare	Psychiatric disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Stress.

Data from ClinicalTrials.gov NCT01009060 adverse events section.

Sponsor's own description

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

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Histamine pharmacology and new CNS drug targets.
   Tiligada E, Kyriakidis K, Chazot PL, Passani MB. · · 2011 · cited 73× · PMID 22070192 · DOI 10.1111/j.1755-5949.2010.00212.x
2. Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: relevance to Alzheimer's disease, ADHD, schizophrenia, and drug abuse.
   Vohora D, Bhowmik M. · · 2012 · cited 48× · PMID 23109919 · DOI 10.3389/fnsys.2012.00072
3. The Histaminergic System in Neuropsychiatric Disorders.
   Cheng L, Liu J, Chen Z. · · 2021 · cited 30× · PMID 34572558 · DOI 10.3390/biom11091345
4. Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer's Disease, Parkinson's Disease, and Autism Spectrum Disorder.
   Thomas SD, Abdalla S, Eissa N, Akour A, et al · · 2024 · cited 18× · PMID 39065682 · DOI 10.3390/ph17070831
5. In Silico Approaches to Developing Novel Glycogen Synthase Kinase 3β (GSK-3β).
   Goyal S, Singh M, Thirumal D, Sharma P, et al · · 2023 · cited 5× · PMID 37893156 · DOI 10.3390/biomedicines11102784