Study to Evaluate Safety and Tolerability of Single Ascending Doses of Multiple Formulations of PF-06650833 in Healthy Subjects Under Fasted and Fed Conditions

Study Overview
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Brief Summary
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This single ascending dose study is the first evaluation of PF-06650833 in humans. The goals are to assess the safety, tolerability and blood levels of ascending doses of multiple formulations of PF-06650833 and to perform a preliminary assessment of the effect of food on exposure, in healthy subjects.

Official Title
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A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Substitution, Crossover, Single Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Pf 06650833 Delivered In Multiple Formulations In Healthy Subjects Under Fasted And Fed Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06650833
* Drug: Placebo
* Drug: PF-06650833
* 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, inclusive. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Exclusion Criteria: Screening supine blood pressure 100 mm Hg (systolic) or 50 mm Hg (diastolic); or 140 mm Hg (systolic) or 90 mm Hg (diastolic) following at least 5 minutes of supine rest. If blood pressure (BP) is 140 mm Hg (systolic) or 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility. Pulse or heart rate (HR) >100 bpm after at least 5 minutes of rest. If the pulse/HR is >100 bpm, the pulse/HR should be repeated two more times (separated by at least 2 minutes) and the average of the three pulse/HR values should be used to determine the subject's eligibility.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (1-1000mg) Immediate Release formulation<br> | Drug: PF-06650833<br>* Subjects will receive sequential single escalating doses of 1-1000 mg of Immediate Release of PF-06650833 (as solution/suspension) under fed and / or fasted conditions.<br>|
| Placebo Comparator: Immediate Release Placebo arm<br> | Drug: Placebo<br>* Subjects will receive sequential single escalating doses of PF-06650833 matching placebo (as solution/suspension) under fed and/ or fasted conditions.<br>|
| Experimental: (10-500) mg Modified Release formulation<br> | Drug: PF-06650833<br>* Subjects will receive sequential single escalating doses of 10-500 mg of Modified Release of PF-06650833 (as capsule) under fed and / or fasted conditions.<br>|
| Placebo Comparator: Modified Release Placebo arm<br> | Drug: Placebo<br>* Subjects will receive sequential single escalating doses of PF-06650833 matching placebo (as capsule) under fed and/ or fasted conditions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events |  | Baseline-5 days | 
| Changes from baseline in vital signs ( blood pressure, pulse rate, respiratory rate and orthostatic blood pressure) |  | Baseline-5 days | 
| Changes from baseline in ECG parameters (standard 12 lead ECG and telemetry) | Quantitative changes in ECG intervals | Baseline-5 days | 
| Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology, chemistry (including, cardiac enzymes CK, CK MB and cardiac Troponin I), serum myoglobin, urinalysis |  | Baseline-5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax, Tmax, AUClast, AUCinf, CL/F, Vz/F, Cmax(dn), AUCinf(dn), AUClast(dn), t½, mean residence time (MRT) for IR and MR formulations under fasted condition |  | Baseline-5 days | 
| Cmax, Tmax, AUClast, AUCinf, CL/F, Vz/F, Cmax(dn), AUCinf(dn), AUClast(dn), t½, mean residence time (MRT) for IR and MR formulations under fed condition |  | Baseline-5 days |