Evaluation Of PF-00572778 And Alprazolam On Naloxone Challenge In Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
PF-00572778, a CRH antagonist, is expected to attenuate adrenocorticotropin (ACTH) and cortisol responses to naloxone by blocking the effect of the CRH increases induced by naloxone at the postsynaptic receptors. Demonstration of a statistically significant attenuation of naloxone induced increases in cortisol and/or ACTH concentrations by PF-00572778 compared to placebo would thus constitute proof of mechanism for the compound. Therefore, this study is to evaluate pharmacodynamic effects of PF-00572778 following naloxone challenge in healthy subjects.

Official Title
-----------------
A Phase I, Randomized, Placebo Controlled, Parallel Group, Single Dose Study To Evaluate The Effects Of PF-00572778 And Alprazolam On A Naloxone Challenge In Healthy Adult Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: alprazolam
* Other: Placebo
* Drug: PF-00572778


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 45 years; Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight >50 kg (110 lbs). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease; Family (1st degree relatives) and personal history of meeting Diagnostic and Statistical Manual -IV (DSM-IV) criteria for alcohol abuse or dependence.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: alprazolam<br>* tablet, 0.5 mg, single dose, only on Day 7 of the study<br>|
| Placebo Comparator: 2<br> | Other: Placebo<br>* solution, matching placebo to 500 mg PF-00572778, single dose, Days 1 and 7 of the study<br>|
| Experimental: 3<br> | Drug: PF-00572778<br>* solution, 500 mg, single dose, only on Day 7 of the study<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the cortisol concentration time curve from 0 to 3 hours ( AUC(0-3) ) following naloxone challenge |  | 1st day on treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) |  | 1st day on treatment | 
| Time to reach the maximum observed serum concentration (Tmax) |  | 1st day on treatment | 
| Safety laboratory tests, vital signs, ECGs, adverse events monitoring, and physical<br>examinations |  | 34 days (weekly) | 
| Peak concentrations for plasma cortisol and ACTH |  | 1st day on treatment | 
| Area under the concentration-time curve from time = 0 to time of the last quantifiable serum PF-00572778 concentration (AUClast) |  | 2nd day on treatment (Days 6-7) | 
| Area under the ACTH concentration curve from 0 to 3 hours ( AUC(0-3) ) following naloxone challenge |  | 1st day on treatment |