A Single and Multiple Dose Study of PF-05221304 in Healthy Japanese Adults

Study Overview
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Brief Summary
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The current study is designed to evaluate the safety, tolerability and pharmacokinetics of PF-05221304 in healthy Japanese adult subjects following single and multiple dose administration.

Official Title
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A Phase 1, 2-part Study Of Pf-05221304 In Healthy Japanese Adults: Part 1 - Randomized, Double-blind, Crossover, Single Dose Assessment Of Pharmacokinetics And Safety; Part 2- Randomized, Double-blind, Placebo-controlled, Multiple Dose Assessment Of Safety, Tolerability And Pharmacokinetics Of Pf-05221304

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-05221304
* Drug: PF-05221304
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects who, at the time of screening, are between the ages of 20 and 55 years, inclusive. Body mass index (BMI) of 17.5-30.5 kg/m2 inclusive; and a total body weight >50 kg (110 lb). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) or clinical findings at Screening.

Ages Eligible for Study
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Minimum Age: 20 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A_Active<br>3 single doses treatment of PF-05221304 | Drug: PF-05221304<br>* 3, 10, 50 mg<br>|
| Experimental: Cohort B_Active<br>Repeated doses of PF-05221304 | Drug: PF-05221304<br>* 50 mg multiple dose<br>|
| Placebo Comparator: Cohort B_Placebo<br>Repeated doses of placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (AUClast) |  | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort A: Maximum observed plasma concentration (Cmax) |  | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort A: Time to reach Cmax (Tmax) |  | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort A: Area under the plasma concentration time profile from time zero extrapolated to infinite time (as data permit) (AUCinf) |  | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort A: Terminal half life (as data permit) (t1/2) |  | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort A: Apparent clearance (as data permit) (CL/F) |  | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort A: Apparent volume of distribution (as data permit) (Vz/F) |  | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Number of Subjects experiencing an Adverse Event | Assessment of adverse events (AEs), clinical laboratory tests, vital signs (including blood pressure and pulse rate) and 12 lead ECG. | Screening up to 28 days after last dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Number of Subjects experiencing an Adverse Event | Assessment of adverse events (AEs), clinical laboratory tests, vital signs (including blood pressure and pulse rate) and 12 lead ECG. | Screening up to 28 days after last dose of study medication | 
| Cohort B: Area under the plasma concentration time profile from time zero to time τ (tau), the dosing interval (ACUtau)(Day 1) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours post dose | 
| Cohort B: Area under the plasma concentration time profile from time zero to time τ (tau), the dosing interval (ACUtau)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Maximum plasma concentration during the dosing interval (Cmax)(Day 1) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours post dose | 
| Cohort B: Maximum plasma concentration during the dosing interval (Cmax)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Time to reach Cmax (Tmax)(Day 1) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours post dose | 
| Cohort B: Time to reach Cmax (Tmax)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Minimum plasma concentration during the dosing interval (Cmin)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Peak trough ratio (PTR)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Observed accumulation ratio (Rac)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Observed accumulation ratio for Cmax (Rac,Cmax)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Terminal half life (t1/2)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Apparent volume of distribution (Vz/F)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 
| Cohort B: Apparent clearance (CL/F)(Day 14) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-05221304, PK, Japanese, NASH, ACC inhibitor