A Study In Healthy Volunteers To Assess The Safety, Tolerability, And Relative Oral Bioavailability Of Three Formulations Of PH-797804

Study Overview
=================
Brief Summary
-----------------
There is no difference in the rate and extent of absorption of the material sparing tablet (MST), the Phase2b/3 formulation (P2b/3) with sodium lauryl sulphate (SLS) and the p2b/3 formulation without SLS.

Official Title
-----------------
A Phase 1, Randomized, Open Label, Single Dose, 3 Treatment, Two Period, Balanced Incomplete Block Study In Healthy Fasted Volunteers To Assess The Safety, Tolerability, And Relative Oral Bioavailability Of A 6 Mg Dose Of The PH-797804 Material Sparing Tablet (MST) And Two Modified Versions Of The MST Formulation With And Without The Solubilizing Agent Sodium Lauryl Sulphate (SLS)

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

Intervention / Treatment
-----------------
* Drug: PH-797804 material sparing tablet
* Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate
* Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate
* Drug: PH-797804 material sparing tablet
* Drug: PH-797804 material sparing tablet
* Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate
* Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate
* Drug: PH-797804 material sparing tablet
* Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate
* Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate
* Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate
* Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and female subjects of non-childbearing potential between the ages of 21 and 55. No evidence of active or latent TB. An informed consent document signed and dated by the subject. Exclusion Criteria: Evidence, including abnormal clinical laboratory parameters, eg, liver enzyme elevations, or a history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy) or any active GI disease (including any relevant surgery). Any current and clinically significant skin lesions as described in Common Terminology Criteria for Adverse Events for Dermatology (CTCAE) Version 3. A clinically significant skin lesion is defined as Grade 1 (mild) for rash and pruritus, and Grade 2 (moderate) or above for all other lesions (see Short Name description in CTCAE for specific description of lesion). Use of prescription or nonprescription drugs, vitamins and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

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

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

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br> | Drug: PH-797804 material sparing tablet<br>* oral, 6mg, single dose<br>Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate<br>* oral, 6mg, single dose<br>|
| Experimental: Sequence 2<br> | Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate<br>* oral, 6mg, single dose<br>Drug: PH-797804 material sparing tablet<br>* oral, 6mg, single dose<br>|
| Experimental: Sequence 3<br> | Drug: PH-797804 material sparing tablet<br>* oral, 6mg, single dose<br>Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate<br>* oral, 6mg, single dose<br>|
| Experimental: Sequence 4<br> | Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate<br>* oral, 6mg, single dose<br>Drug: PH-797804 material sparing tablet<br>* oral, 6mg, single dose<br>|
| Experimental: Sequence 5<br>oral, 6mg, single dose | Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate<br>* oral, 6mg, single dose<br>Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate<br>* oral, 6mg, single dose<br>|
| Experimental: Sequence 6<br>oral, 6mg, single dose | Drug: PH-797804 Phase2b/3 with sodium lauryl sulphate<br>* oral, 6mg, single dose<br>Drug: PH-797804 Phase2b/3 without sodium lauryl sulphate<br>* oral, 6mg, single dose<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf) |  | predose to day 7 of treatment period | 
| Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) |  | predose to day 7 of treatment period | 
| Maximum observed concentration within the dosing interval (Cmax) |  | predose to day 7 of treatment period | 
| Time for Cmax (Tmax) |  | predose to day 7 of treatment period | 
| Terminal half-life (t1/2) |  | predose to day 7 of treatment period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pharmacokinetic, single dose bioequivalence study, balanced incomplete block design, PH-797804, P38 kinase inhibitor