Single Dose Study to Assess the Safety, Tolerability and Pharmacokinetics(PK) of PF-06865571

Study Overview
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Brief Summary
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The current study is the first clinical trial proposed with PF-06865571. It is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) following administration of single doses of PF-06865571 to healthy adult subjects.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Single Escalating Oral Doses Of Pf-06865571 In Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06865571
* Drug: PF-06865571
* Drug: PF-06865571
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and female of non-childbearing potential; Age of 18-55, inclusive; Body Mass Index 22.5 to 35.4 kg/m2, inclusive; Body weight >50 kg; Not on any prescription or non-prescription drugs within 7 days or 5 half-lives prior to first dose. Exclusion Criteria: Evidence of history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergises, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) Any condition possibly affecting drug absorption (eg, gastrectomy). A positive urine drug test. History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening. Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer). Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. History of sensitivity to heparin or heparin induced thrombocytopenia. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb). Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product. Subjects 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: (1)Aspartate aminotransferase (AST), alanine aminotransferase (ALT) level, or total bilirubin > upper limit of normal (ULN); (2) For optional Cohort 3 only, AST or ALT greater or equal to 1.5 × ULN, provided that data from Cohorts 1 and 2 support this limit; (3) • Subjects 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 less than or equal to ULN plus ALT and AST are less than or equal to ULN plus alkaline phosphatase, hemoglobin, and reticulocyte count are all less than or equal to ULN. Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of this protocol. Subjects who are investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior 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
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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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1_Active and Matching Placebo<br> | Drug: PF-06865571<br>* Single ascending dose of PF-06865571 as extemporaneously prepared solution/suspension, once every 2 week in a cross over study: 5 mg, 50 mg, 500 mg, TBD (to be determined)/2000 mg.<br>Drug: Placebo<br>* Matching Placebo for PF-06865571 for each cohort.<br>|
| Experimental: Cohort 2_Active and Matching Placebo<br> | Drug: PF-06865571<br>* Single ascending dose of PF-06865571 as extemporaneously prepared solution/suspension, once every 2 week in a cross over study: 15 mg, 150 mg, 1000 mg, TBD/2000 mg.<br>Drug: Placebo<br>* Matching Placebo for PF-06865571 for each cohort.<br>|
| Experimental: Cohort 3_Active and Matching Placebo<br> | Drug: PF-06865571<br>* Single repeated (TBD mg) dose as extemporaneously prepared solution/suspension of PF-06865571.<br>Drug: Placebo<br>* Matching Placebo for PF-06865571 for each cohort.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events (AEs) | Number of participants with reported adverse events | Screening up to 35 days after last dose of study medication | 
| Number of subjects with laboratory tests findings of potential clinical importance | Number of participants with potentially clinically important laboratory test findings | Baseline (Day 0) up to 14 days after last dose of study medication | 
| Number of subjects with vital signs findings of potential clinical importance | Number of participants with potentially clinically important vital sign measurements | Baseline (Day 0) up to 14 days after last dose of study medication | 
| Number of subjects with electrocardiogram (ECG) findings of potential clinical importance | Number of participants with potentially clinically important ECG findings | Baseline (Day 0) up to 14 days after last dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06865571 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time for PF-06865571 | AUC (0-infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (t-infinity). | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Dose normalized AUClast for PF-06865571 | dose normalized AUC will be analysed using a mixed model appropriate to the study design | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Dose normalized AUCinf for PF-06865571 | Following log-transformation, dose normalized AUCinf will be analysed using a mixed model appropriate to the study design. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Maximum Observed Plasma Concentration (Cmax) for PF-06865571 | Maximum Observed Plasma Concentration (Cmax) | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Dose normalized Cmax for PF-06865571 | Following log-transformation, dose normalized Cmax will be analysed using a mixed model appropriate to the study design. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Time to Reach Maximum Observed Concentration for PF-06865571 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Plasma Decay Half-Life (t1/2) for PF-06865571 | Plasma Decay Half-Life (t1/2) | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Apparent Oral Clearance (CL/F) for PF-06865571 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period | 
| Apparent Volume of Distribution (Vz/F) for PF-06865571 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post dose in each period |