To compare by neuroimaging techniques and public speaking, the way social anxiety patients
respond after the administration of GW876008, GSK561679, alprazolam and placebo
Inclusion criteria:
- Outpatient with a primary diagnosis of Social Anxiety
- LSAS score of 50 or more.
- Men or women who are between 18 and 64 years of age. Women will be included in this
study only if the reproductive toxicology data available at the time of study start
will allow their inclusion, in accordance with regulatory requirements.
- Body weight > 50 kg and BMI within the range 18. 5 - 31. 0 kg/m2.
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
- The subject must be able to read, comprehend and record information.
- A signed and dated written informed consent is obtained from the subject.
- Subjects willing to restrict alcohol intake to 4 unit of alcohol or less per day. A
unit is equivalent to 300 ml of beer or one measure of spirits or one glass of wine.
- Women must be of non child bearing potential or commit to consistent and correct use
of an acceptable method of birth control that must be recorded on the source
documentation at screening and verified for continued compliance at each visit; GSK
acceptable contraceptive methods, when used consistently and in accordance with both
the product label and the instructions of a physician, are as follows:
- Subjects with a history of peptic ulcer disease (PUD) with a known aetiology must
provide documentation by a gastroenterologist of the aetiology of the PUD and that
effective treatment was provided with full eradication of ulcers and symptoms.
Exclusion criteria:
- Any concomitant drug dosing 24 h before each dosing.
- Any history of a clinically significant abnormality of the neurological system
(including dementia and other cognitive disorders or significant head injury) or any
history of seizure (excluding febrile seizure).
- Subjects with an unstable medical disorder or a disorder that would likely interfere
with the action, absorption, distribution, metabolism or excretion of GW876008,
GSK561679 or alprazolam, may pose a safety concern, or interfere with accurate
assessment of safety.
- The subject has a current or recent (within six months) documented gastrointestinal
disease
- Subject has symptoms of the presenting illness which are better accounted for by
another diagnosis or subjects who meet DSM-IV criteria for any other Axis I disorder
as a primary diagnosis currently or within 6 months prior to the screening visit or A
current DSM-IV-TR diagnosis of Antisocial or Borderline Personality Disorder,
Dementia, or another current DSM-IV-TR Axis II diagnosis that would suggest
nonresponsiveness to pharmacotherapy or non-compliance with the protocol; or A current
(or within six months prior to the Screening visit) diagnosis of anorexia nervosa or
bulimia; or Subjects with a history of Schizophrenia, Schizoaffective Disorder, or a
Bipolar Disorder.
- HAMD-17 score greater than 15.
- Subjects who are currently receiving regularly scheduled psychotherapy (individual or
group, including cognitive behavioural therapy), plan to initiate psychotherapy during
the trial or have received regularly scheduled psychotherapy during the 12 week period
prior to the Screening Visit.
- Subjects have any laboratory abnormality that in the investigator's judgment is
considered to be clinically significant and not resolved by the Randomization Visit.
- The subject has a semi-supine systolic blood pressure less than 90mmHg (85mmHg for
females) or greater than 140mmHg or a semi-supine diastolic blood pressure of less
than 45mmHg or greater than 90mmHg; or a pulse rate less than 40bpm or more than
90bpm.
- Women who have a positive serum Human Chorionic Gonadotropin (HCG) pregnancy test at
screen visit, a positive urine dipstick test at Randomization, or who are lactating or
planning to become pregnant within the next 2weeks after the Follow Up Visit.
- The subject has participated in a clinical trial and has received a drug or a new
chemical entity within 60 days or 5 half-lives, or twice the duration of the
biological effect of any drug(whichever is longer) prior to the first dose of current
study medication.
- Exposure to more than four new chemical within 12 months prior to the first dosing
day.
- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the physician responsible,
contraindicates their participation.
- As a result of any of the medical interview, physical examination or screening
investigations the physician responsible considers the subject unfit for the study.
- History of long QT syndrome (personal or family) or other cardiac conduction disorder,
or other clinically significant cardiac disease.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John'sWort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and sponsor the
medication will not interfere with the study procedures or compromise subject safety
- Subjects who, in the opinion of the investigator, would be noncompliant with the visit
schedule or study procedures (e. g., illiteracy, planned vacations, or planned
hospitalizations during the study).
- Subjects who are not euthyroid as evidenced by normal TSH. Subjects maintained with
thyroid medication must be euthyroid for a period of at least six months prior to the
screen visit.
- Subject's level of FSH falling outside normal range
- Subjects with diabetes or high risk of diabetes based on a documented history of
impaired glucose tolerance.
- Subjects have any electrocardiographic (ECG) parameter outside of the
Sponsor-specified ranges at either screen or randomization visit.
- Subjects who have had electroconvulsive therapy (ECT) or transcranial magnetic
stimulation within the 6 months prior to the Screening Visit.
- Subjects, who are left-handed.
- The subject has a positive pre-study urine drug/ breath alcohol screen. A minimum list
of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine,
Opiates, Cannabinoids and Benzodiazepines.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.
- Documented history of hepato-biliary disease or abnormality in hepatic enzymesat
screening
