PK And Safety Study Of PF-04171327 In Healthy Japanese And Western Subjects In Fasting And Fed Conditions

Study Overview
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Brief Summary
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This Phase 1 study is the first clinical trial in Japanese subjects. This study is designed to evaluate the single- and multiple-dose pharmacokinetics, safety and tolerability of PF-04171327 oral tablet in healthy adult Japanese and Western subjects in fasting and fed conditions.

Official Title
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A Phase 1, Randomized, Subject- And Investigator Blind, Sponsor Open, Placebo Controlled, Single- And Multiple-Dose Escalation Study Of PF-04171327 In Healthy Adult Japanese And Western Subjects In Fasting And Fed Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-04171327
* Drug: PF-04171327
* Drug: PF-04171327
* Drug: Placebo
* Drug: PF-04171327
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects of non childbearing potential between the ages of 18 and 55 years. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >45 kg (99 lbs). Japanese subjects who have four Japanese grandparents born in Japan. Exclusion Criteria: Confirmed fasting glucose more than 100 mg/dL at Screening and Day 0 in both Cohort A and B. Corticosteroid use of more than 5 mg prednisone equivalent per day for more than 6 weeks. Evidence or history of clinically significant hematological (including anemia), renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose<br> | Drug: PF-04171327<br>* Oral single 5 mg dose as one 5 mg tablet<br>Drug: PF-04171327<br>* Oral single 10 mg dose as one 10 mg tablet<br>Drug: PF-04171327<br>* Oral single 30 mg dose as three 10 mg tablets<br>Drug: Placebo<br>* Oral single dose as matching placebo<br>|
| Experimental: Multiple dose<br> | Drug: PF-04171327<br>* Oral multiple 20 mg doses as two 10 mg tablets for 12 days<br>Drug: Placebo<br>* Oral multiple doses as matching placebo for 12 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic parameters for PF-00251802 : Cmax |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for PF-00251802 : Tmax |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for PF00251802 : AUC(0-last) |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for PF-00251802 : As data permit AUC(0-inf) |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for PF-00251802 : As data permit t1/2 |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): Cmax |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): Tmax |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): AUC(0-last) |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): As data permit AUC(0-inf) |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): As data permit t1/2 |  | Day 1 to Day 4 in each period of Cohort A | 
| Plasma pharmacokinetic parameters for PF-00251802: Cmax for Day 1 and Day 12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for PF-00251802: Tmax for Day 1 and Day 12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for PF-00251802: AUCtau for Day 1 and Day 12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for PF-00251802: As data permit t1/2 for Day12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for PF-00251802: As data permit Rac (accumulation ratio = Day 12 AUCtau/Day 1 AUCtau) for Day12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for PF-00251802: Ctrough |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): Cmax for Day 1 and Day 12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): Tmax for Day 1 and Day 12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): AUCtau for Day 1 and Day 12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): As data permit t1/2 for Day12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): As data permit Rac (accumulation ratio = Day 12 AUCtau/Day 1 AUCtau) for Day12 |  | Day 1 to Day 15 in Cohort B | 
| Plasma pharmacokinetic parameters for N-oxide metabolite (PF-04015475): Ctrough |  | Day 1 to Day 15 in Cohort B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers for bone effects: Serum procollagen type 1 N-terminal propeptide (P1NP), serum C terminal telopeptide of type I collagen (CTX), serum osteocalcin and urine N terminal telopeptide of type I collagen (uNTX). |  | Day 0 to Day 15 in Cohort B | 
| Biomarkers for carbohydrate and metabolic: Plasma cortisol, serum glucose, plasma insulin and serum adiponectin. |  | Day 0 to Day 15 in Cohort B | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Pharmacokinetics, food effect, Healthy Japanese, rheumatoid arthritis