Study to Assess Pharmacokinetics, Safety and Tolerability of PF-04965842 in Chinese Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics, safety and tolerability of PF-04965842 after single dose and once-daily multiple-doses in Chinese healthy participants.

Detailed Description
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This is a Phase 1, open-label, single-arm, single- and multiple-dose study to assess the pharmacokinetics, safety and tolerability of PF-04965842 in Chinese healthy participants.

Official Title
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A PHASE 1, OPEN-LABEL, SINGLE-ARM, SINGLE DOSE AND MULTIPLE DOSES STUDY TO ASSESS PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN CHINESE HEALTHY PARTICIPANTS

Conditions
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HEALTHY

Intervention / Treatment
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* Drug: PF-04965842


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) of 19 to 26 kg/m2; and a total body weight >50 kg. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Exclusion Criteria: Evidence or clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic (including alcoholic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and hereditary liver diseases), psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb) and serological reaction of syphilis. As an exception, a positive hepatitis B surface antibody (HBsAb) finding as a result of participant vaccination is permissible. Evidence or history of clinically significant dermatological condition (eg, contact dermatitis or psoriasis) or visible rash present during physical examination. History of tuberculosis (TB) or active or latent or inadequately treated infection, positive QuantiFERON- TB Gold test or positive chest radiographs for active tuberculosis infection. Any history of chronic infections, any history of recurrent infections, any history of latent infections, or any acute infection within 2 weeks of baseline. History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster. Have any malignancies or have a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ. A positive urine drug test. Screening sitting blood pressure (BP) >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >=1.5 × upper limit of normal (ULN); Total bilirubin level >1 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is <=1 × ULN.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Intervention Model: Single Group Assignment
Interventional Model Description: open-label, single-arm, single- and multiple-dose study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04965842<br>Following an overnight fast for at least 10 hours, participants will receive PF-04965842 oral single dose of 200 mg (2 × 100 mg tablets) on Day 1, at approximately 08:00 am plus or minus 2 hours in the morning. On Days 3 to 8, participants will receive PF-04965842 oral dose of 200 mg (2 × 100 mg tablets) QD in the morning at approximately similar clock hour as on Day 1. On Day 3 and Day 6-8, the dosing of PF-04965842 will be after collection of pre-dose blood samples (under fasted condition for at least 10 hours). On Day 8, the dosing will be under fasted condition at approximately 8:00 am plus or minus 2 hours in the morning. | Drug: PF-04965842<br>* For this study, the investigational product is PF-04965842 (provided as 100 mg tablet). PF-04965842 100 mg tablets will be provided by Pfizer. Investigational product will be presented to the participants in individual dosing containers<br>* Other names: condition at approximately 8:00 am plus or minus 2 hours in the morning.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | PK parameters derived from plasma PF-04965842 concentration | The pharmacokinetic samples will be collected at 0 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours after dosing on Day 1 | 
| Maximum Observed Plasma Concentration (Cmax) | PK parameters derived from plasma PF-04965842 concentration | The pharmacokinetic samples will be collected at 0 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours after dosing on Day 1 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | PK parameters derived from plasma PF-04965842 concentration | The pharmacokinetic samples will be collected at 0 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours after dosing on Day 1 | 
| Area under the plasma concentration time profile from time zero to time tau | PK parameters derived from plasma PF-04965842 concentration | The pharmacokinetic samples will be collected at 0 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours after dosing on Day 1 and Day8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Screening up to follow up (71 days) | 
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Tests | Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. | Screening up to follow up (71 days) | 
| Number of Pariticipants With Clinically Significant Change From Baseline in Vital Signs | Sitting BP will be measured with the participant's arm supported at the level of the heart, with feet flat on the floor and back supported, and recorded to the nearest mm Hg after approximately 5 minutes of rest. | Screening up to follow up (71 days) | 
| Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings | All scheduled ECGs should be performed after the participant has rested quietly for at least 10 minutes in a supine position. | Screening up to follow up (71 days) |