To Investigate Effects GSK561679 on Part of the Body's System That Controls the Balance of Many of the Hormones.

Study Overview
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Brief Summary
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A study to investigate the effects GSK561679 on part of the body's system that controls the balance of many of the hormones (including cortisol).

Official Title
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Placebo-Controlled, Randomized, Blinded, Double-Dummy, Crossover Study to Investigate the Attenuation of ACTH Activation Induced by Metyrapone With a Single Dose of GSK561679 or Alprazolam in Healthy Volunteers

Conditions
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Depressive Disorder and Anxiety Disorders

Intervention / Treatment
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* Drug: metyrapone
* Drug: alprazolam
* Drug: placebo
* Drug: GSK561679


Participation Criteria
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Eligibility Criteria
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Inclusion: Healthy male subjects non-smoker normal ECG Exclusion: shift workers vegetarians persons who travel distances persons participating in a psychology or psychiatry course

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Session 1<br>Subjects will be randomized to receive Dose 1 of Metyrapone 0.04 gram per kilogram (g/kg) and Dose 2 of AEBCD sequence. In AEBCD sequence A is placebo, E Alprazolam, B GSK6561679 10 milligram (mg), C GSK6561679 50 mg and D GSK6561679 400 mg. Wash-out period will be of 7 days. | Drug: metyrapone<br>* Metyrapone will be available as 250 mg dose capsule.<br>Drug: alprazolam<br>* Alprazolam capsules will be available with dose strength of 0.25mg<br>Drug: placebo<br>* GSK561679 placebo tablets visually match the active GSK561679 tablets. Placebo to match Alprazolam is a hard gelatine capsule that visually matches active Alprazolam capsules.<br>Drug: GSK561679<br>* GSK561679 tablets will be available with dose strength of 50, 10 and 200 mg.<br>* Other names: Single dose of alprazolam;|
| Experimental: Session 2<br>Subjects will be randomized to receive Dose 1 of Metyrapone 0.04 g/kg and Dose 2 of BACED sequence. In BACED sequence B is GSK6561679 10 mg, A placebo, C GSK6561679 50 mg, E Alprazolam, and D GSK6561679 400 mg. Wash-out period will be of 7 days. | Drug: metyrapone<br>* Metyrapone will be available as 250 mg dose capsule.<br>Drug: alprazolam<br>* Alprazolam capsules will be available with dose strength of 0.25mg<br>Drug: placebo<br>* GSK561679 placebo tablets visually match the active GSK561679 tablets. Placebo to match Alprazolam is a hard gelatine capsule that visually matches active Alprazolam capsules.<br>Drug: GSK561679<br>* GSK561679 tablets will be available with dose strength of 50, 10 and 200 mg.<br>* Other names: Single dose of alprazolam;|
| Experimental: Session 3<br>Subjects will be randomized to receive Dose 1 of Metyrapone 0.04 g/kg and Dose 2 of CBEAD sequence. In CBEAD sequence C is GSK6561679 50 mg, B GSK6561679 10 mg, E Alprazolam, A placebo, and D GSK6561679 400 mg. Wash-out period will be of 7 days. | Drug: metyrapone<br>* Metyrapone will be available as 250 mg dose capsule.<br>Drug: alprazolam<br>* Alprazolam capsules will be available with dose strength of 0.25mg<br>Drug: placebo<br>* GSK561679 placebo tablets visually match the active GSK561679 tablets. Placebo to match Alprazolam is a hard gelatine capsule that visually matches active Alprazolam capsules.<br>Drug: GSK561679<br>* GSK561679 tablets will be available with dose strength of 50, 10 and 200 mg.<br>* Other names: Single dose of alprazolam;|
| Experimental: Session 4<br>Subjects will be randomized to receive Dose 1 of Metyrapone 0.04 g/kg and Dose 2 of ECABD sequence. In ECABD sequence E is Alprazolam, C is GSK6561679 50 mg, A placebo, B GSK6561679 10 mg and D GSK6561679 400 mg. Wash-out period will be of 7 days. | Drug: metyrapone<br>* Metyrapone will be available as 250 mg dose capsule.<br>Drug: alprazolam<br>* Alprazolam capsules will be available with dose strength of 0.25mg<br>Drug: placebo<br>* GSK561679 placebo tablets visually match the active GSK561679 tablets. Placebo to match Alprazolam is a hard gelatine capsule that visually matches active Alprazolam capsules.<br>Drug: GSK561679<br>* GSK561679 tablets will be available with dose strength of 50, 10 and 200 mg.<br>* Other names: Single dose of alprazolam;|
| Experimental: Session 5<br>Subjects will be randomized to receive Dose 1 of Metyrapone 0.04 g/kg and Dose 2 of GSK561679 400 mg and alprazopam placebo. Wash-out period will be of 7 days. | Drug: metyrapone<br>* Metyrapone will be available as 250 mg dose capsule.<br>Drug: alprazolam<br>* Alprazolam capsules will be available with dose strength of 0.25mg<br>Drug: placebo<br>* GSK561679 placebo tablets visually match the active GSK561679 tablets. Placebo to match Alprazolam is a hard gelatine capsule that visually matches active Alprazolam capsules.<br>Drug: GSK561679<br>* GSK561679 tablets will be available with dose strength of 50, 10 and 200 mg.<br>* Other names: Single dose of alprazolam;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood levels of ACTH: over 24 hours |  | Over 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood levels of GSK561679, metyrapone, alprazolam, cortisol: over 24 hours Questionnaires: each visit Safety (ECG/vital signs/Adverse Events/ laboratory): over 24 hours |  | Over 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPA axis,, Healthy volunteers, hormones,, GSK561679,, cortisol,