A Study To Compare The Putative Anxiolytic Effect Of 2 New Drugs In Subjects With Social Anxiety Disorder

NCT00555139 | Completed Phase 1

• 1 other identifier: CRH108571
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 8

Brief Summary

To compare by neuroimaging techniques and public speaking, the way social anxiety patients respond after the administration of GW876008, GSK561679, alprazolam and placebo

Conditions

Social Phobia

Keywords

anxiety,; depression,; fMRI; CRF-1 antagonists,

Outcome Measures

Primary Outcomes (1)

• Changes of fMRI activation in amygdala of subjects with SAD during an emotional task after having received different compounds. Change in the VAS score in response to Public Speaking stress after having received different compounds.

  over 6 weeks

Secondary Outcomes (10)

• Changes of fMRI activation patterns in all brain areas in subjects with SAD during an emotional task or resting state. Changes of cortisol levels and other stress indicators in response to Public Speaking stress.

  over 6 weeks

• Pk samples:

  2 hours,4-5, 8hours post-dose (over 3 weeks, week 1,2&3)

• Cortisol, ACTH:

  5hours 20min,5hours 35 min, 6hours & 7hours post dose (over 6 weeks, week 1,2,3 &6)

• Indicators of physiological state during the fMRI session:

  pre-dose, 5hours 20mins, 5hours 43mins, 6 hours, 6hours 20mins (over 6 weeks, week 1,2,3 &6)

• Heart rate (HR), Respiratory rate (RR), ventilation (pneumatic pletismography), and carbon dioxide percutaneous measurements monitored during the whole procedure (control and exploratory profile tests).

  pre-dose, 5hours 20mins, 5hours 43mins, 6 hours, 6hours 20mins (over 6 weeks, week 1,2,3 &6)

Study Arms (2)

GW876008

EXPERIMENTAL

The subjects will be randomized to one of the six sequences A/B/D A/D/B B/A/D B/D/A D/A/B D/B/A across three treatment periods where A represents placebo, B represents GW876008 and D represents alprazolam.

Drug: GW876008 tablet; Drug: alprazolam; Drug: Placebo

GSK561679

EXPERIMENTAL

The subjects will be randomized to one of the six sequences A/C/D A/D/C C/A/D C/D/A D/A/C D/C/A across three treatment periods where A represents placebo, C represents GSK561679 and D represents alprazolam.

Drug: GSK561679 tablet; Drug: alprazolam; Drug: Placebo

Interventions

GSK561679 tablet DRUG

GSK561679 tablets are white film-coated tablets, containing 200 (milligrams) mg of the free base, GSK561679A.

GSK561679

GW876008 tablet DRUG

GW876008 tablets are white to off-white round film-coated tablets, containing 100 mg of GW876008X (free base).

GW876008

alprazolam DRUG

Alprazolam capsules 0.25 mg are hard gelatine capsules containing 1 tablet of commercial alprazolam (Xanax 0.25).

Also known as: GSK561679, GW876008

GSK561679; GW876008

Placebo DRUG

GW876008 placebo tablets will visually match the active GW876008 tablets. GSK561679 placebo tablets will visually match the active GSK561679 tablets. Placebo to match Alprazolam is a hard gelatine capsule that will visually match the active but containing only a filler.

GSK561679; GW876008

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Outpatient with a primary diagnosis of Social Anxiety
• LSAS score of 50 or more.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Barcelona, 08025, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, E-08003, Spain

Location

GSK Investigational Site

Barcelona, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

Location

GSK Investigational Site

Mataro (Barcelona), Spain

Location

GSK Investigational Site

Sabadell (Barcelona), 08208, Spain

Location

GSK Investigational Site

Terrassa - Barcelona, 08227, Spain

Location

Related Links

• Results for study CRH108571 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Phobia, Social; Anxiety Disorders; Depression

Interventions

NBI 77860; GW 876008; Alprazolam

Condition Hierarchy (Ancestors)

Phobic Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2007
• First Posted: November 7, 2007
• Study Start: March 27, 2007
• Primary Completion: January 10, 2008
• Study Completion: January 10, 2008
• Last Updated: August 4, 2017

Record last verified: 2017-08

Locations

ES (8)