A Randomized, Placebo-controlled, Double-dummy, Four-way Crossover Design Study to Investigate the Changes of fMRI BOLD Activation Induced by Emotional Activation Paradigms Following Single Doses of GW876008 and Lorazepam (Comparator) in Healthy Subjects.

GlaxoSmithKline1 site in 1 country26 target enrollmentMarch 2007

ConditionsHealthy Subjects

Drugsplacebo lorazepam GW876008

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Healthy Subjects
Sponsor: GlaxoSmithKline
Enrollment: 26
Locations: 1
Primary Endpoint: Differences in brain activation elicited by Matching Emotional Face Expression paradigm following single oral doses of GW876008 and lorazepam on day 1, sessions 1-4
Status: Completed
Last Updated: 15 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Data suggests that imaging activity of the brain can measure the effects of anti-anxiety drugs. This study will investigate the effect of GW876008 on areas of the brain involved with thinking and emotion

Registry

clinicaltrials.gov

Start Date

March 2007

End Date

December 2007

Last Updated

15 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Eligibility Criteria

Inclusion Criteria

•Healthy males or females aged 18-50 years, inclusive.
•STAI-trait score = or \>
•STAI-state score \<50th percentile of the normal population distribution.
•Female subjects of non-childbearing.
•Female subjects of childbearing potential must agree to use appropriate contraception.
•Healthy subjects, as determined by a responsible physician
•Body weight ≥ 50 kg (110 lbs), and BMI within the range 19-29.9 kg/m2 inclusive.
•Demonstrates no significant evidence of active disease, physical or mental impairment when assessed by qualified personnel
•Non-smoker (abstinence from smoking for at least 6 months before the start of the study).
•Normal electrocardiogram.

Exclusion Criteria

•As a result of any of the medical interview, physical examination, evaluation of mental state and psychiatric history or screening investigations the physician responsible considers the subject unfit for the study.
•Any history of suicidal attempts or behaviour.
•Any history or current diagnosis of a psychiatric illness.
•Any history of an endocrine disorder including, but not limited to, diabetes or disorders of the hypothalamus, pituitary, adrenal, or thyroid glands, or gonadal disorder or dysfunction of the reproductive organs.
•Abnormal pepsinogen I level at screening.
•Liver Function Tests (LFTs) elevated above the reference range at pre-study screening that remain elevated with a repeat LFT
•Any other clinically significant laboratory abnormality.
•Positive faecal occult blood test.
•Positive pre-study urine drug/alcohol breath screen.
•Positive pre-study HIV 1/2, Hepatitis B surface antigen and positive Hepatitis C antibody result within 3 months of the start of the study.

Outcomes

Primary Outcomes

Differences in brain activation elicited by Matching Emotional Face Expression paradigm following single oral doses of GW876008 and lorazepam on day 1, sessions 1-4

Secondary Outcomes

Safety: 12-lead ECG, vital signs, adverse events, clinical labs
GW876008 blood levels(pre-dose & post-dose, sessions 1-4)
clinical rating scales change after dosing: questionnaires collected(pre-dose & up to 6-8 hours post-dose.)
fMRI BOLD neuroanatomical structure of the emotional brain neurocircuitry and connectivity
fMRI BOLD Signal characteristics and connectivity
fMRI BOLD Response in the emotional brain neurocircuitry and occipital cortex.
ETCo2 in mm Hg, to be recorded for the duration of the scan session and be synchronized with the single fMRI procedure timing
Visual Analog Scale (VAS) measurements of sleepiness, alertness, calm, tension, and anxiety performed before dosing (baseline), pre-fMRI session, post-fMRI session and just before leaving the facility.
Association between the anxiety trait (STAI-trait, test battery for neuroticism or liability for Anxiety Disorders) collected at screening and the various pharmacodynamic parameters measured in the various testing conditions.
GW876008 concentration to determine pharmacokinetic parameters to be collected twice per session,
Pharmacogenetic (PGx) assessments
Safety and tolerability of GW876008 to include Vital signs semi-supine; respiratory rate, pulse oximetry and ECG.
Clinical laboratory tests
fMRI BOLD ALS signal.
Heart rate (HR; beats per minute), to be recorded for the whole duration of the scan session and to be synchronized with the single fMRI procedure timing.
Respiratory rate (RR: inspiration per minute), to be recorded for the duration of scan session and be synchronized with the single fMRI procedure timing. .