A Study In Healthy People To Evaluate Safety, Toleration, Pharmacokinetics And Pharmacodynamics Of Multiple Oral Doses Of PF-06743649

Study Overview
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Brief Summary
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The purpose of this study in healthy people is to evaluate safety, toleration and time course of plasma concentration of multiple oral doses of PF-06743649. The pharmacodynamic activity of PF-06743649 will also be assessed. The effect of food on PK of PF-06743649 will also be investigated.

Official Title
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A Phase 1 Double Blind (3rd Party Open) Randomized, Placebo Controlled, Dose Escalation Study To Investigate The Safety,Tolerability, Pharmacokinetics And Pharmacodynamics Of Repeat Doses Of Pf-06743649 With Or Without Food In Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06743649
* Drug: Placebo
* Drug: PF-06743649
* Drug: Placebo
* Drug: PF-06743649
* Drug: Placebo
* Drug: PF-06743649
* Drug: Placebo
* Drug: PF-06743649
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests). Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. Exclusion Criteria: Evidence or 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). Evidence of gout/hyperuricemia, measured sUA >8 mg/dL at screening. Experienced an episode of nephrolithiasis or ureterolithiasis.

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1-PF-06743649 or placebo<br>Subjects will be randomized to receive PF-06743649 or placebo as 2 single doses in periods 1 and 2 either in the fed or fasted state followed by once daily dosing for 14 days in period 3 | Drug: PF-06743649<br>* 40 mg tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days<br>Drug: Placebo<br>* Placebo tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days<br>|
| Experimental: Cohort 2-PF-06743649 or placebo<br> | Drug: PF-06743649<br>* To be decided dose, tablet once daily dosing for 14 days<br>Drug: Placebo<br>* Placebo tablet once daily dosing for 14 days<br>|
| Experimental: Cohort 3-PF-06743649 or placebo<br> | Drug: PF-06743649<br>* To be decided dose, tablet, one time once with a meal and once without a meal, followed by once daily dosing for 14 days<br>Drug: Placebo<br>* Placebo tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days<br>|
| Experimental: Cohort 4-PF-06743649 or placebo<br> | Drug: PF-06743649<br>* To be decided dose, tablet, one time without a meal, followed by once daily dosing for 14 days<br>Drug: Placebo<br>* Placebo tablet one time once without a meal, followed by once daily dosing for 14 days<br>|
| Experimental: Cohort 5-PF-06743649 or placebo<br> | Drug: PF-06743649<br>* Tablet, to be decided dose, once daily, 14 days<br>Drug: Placebo<br>* Tablet, once daily, 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | up to 14 days | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) |  | up to 14 days | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | up to 14 days | 
| Plasma Decay Half-Life (t1/2) |  | up to 14 days | 
| Amount of drug recovered unchanged in urine during the dosing interval (Aetau) |  | up to 14 days | 
| Percent of dose recovered unchanged in urine during the dosing interval(Aetau%) |  | up to 14 days | 
| Renal clearance (CLr) |  | up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in serum uric acid level |  | up to 14 days | 
| Change from baseline in serum levels of xanthine and hypoxanthine |  | up to 14 days | 
| Urinary uric acid levels |  | up to 14 days | 
| Urinary xanthine levels |  | up to 14 days | 
| Urinary hypoxanthine levels |  | up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple dose, safety, tolerability, PK