Study of Commercial and Phase 3 of PF-04965842 Formulations, Estimation of Effect of Food on Commercial Formulation

Study Overview
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Brief Summary
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Part A To measure and compare the amount of study drug in the blood after a single 200 mg dose of study drug given as the commercial tablet formulation and the Phase 3 tablet formulation under fasting conditions To measure and compare the amount of study drug in the blood after a single 200 mg dose given as the variant Phase 3 tablet formulation and the Phase 3 tablet formulation under fasting conditions To estimate the effect of food on the amount of study drug in the blood after a single 200 mg dose of the commercial formulation Part B • To measure and compare the amount of study drug in the blood after a single 200 mg dose given as the commercial tablet formulation and the Phase 3 tablet formulation under fasting conditions Parts A & B To collect samples for genotyping (CYP2C19 and CYP2C9 - enzymes that metabolize [break down] certain medications) o Genotyping is the collection of a small sample of blood that contains your genes To evaluate the safety and tolerability of the study drug after single 200 mg doses of the three different formulations given to healthy participants To measure the amount of study drug in the blood after single doses of the different formulations To collect exploratory samples for biobanking o Biobanking is the collection and storage of blood samples for possible future testing

Detailed Description
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The purpose of this study in healthy participants is to estimate the bioavailability (BA) of the commercial formulation of PF-04965842 and a variant formulation with slower dissolution relative to the Phase 3 formulation, to demonstrate the bioequivalence (BE) of the commercial formulation relative to the Phase 3 formulation, and to estimate the effect of food on the BA of the commercial formulation. This study consists of 2 parts: Part A is to estimate the relative BA (rBA) of single 200 mg doses of the commercial tablet formulation of PF-04965842 and a variant formulation of slower dissolution rate compared to the Phase 3 tablet formulation. The effect of food on the BA of the commercial tablet formulation will also be evaluated. Part B is to establish BE between the Phase 3 and commercial formulations. The study will follow a staged approach as the sample size for BE cannot be determined with currently available information. Therefore, it is proposed to assess the maximum observed concentration (Cmax) and area under the curve (AUC) ratios between the Phase 3 and commercial formulations as well as the within-participant variability of Cmax and AUC values determined in Part A. Based on the results from Part A, the sample size of Part B will be determined and the decision to proceed to Part B will be made.

Official Title
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A PHASE 1, OPEN LABEL, SINGLE-DOSE, CROSSOVER STUDY TO EVALUATE THE BIOEQUIVALENCE OF A COMMERCIAL TABLET FORMULATION OF PF-04965842 RELATIVE TO THE PHASE III TABLET FORMULATION UNDER FASTING CONDITIONS AND THE EFFECT OF FOOD ON THE RELATIVE BIOAVAILABILITY OF THE COMMERCIAL TABLET FORMULATION IN HEALTHY PARTICIPANTS

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: P3-Fast
* Drug: Comm-Fast
* Drug: Vari-Fast
* Drug: Comm-Fed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb) Exclusion Criteria: Any condition possibly affecting drug absorption (eg, gastrectomy). History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis Evidence or history of clinically significant dermatological condition (eg, atopic dermatitis or psoriasis) .History of tuberculosis (TB) (active or latent) or inadequately treated TB infection. History of chronic infections, history of recurrent infections, history of latent infections, .History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent localized dermatomal herpes zoster. 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

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a Phase 1 randomized, open label, single-dose, crossover study in healthy participants to estimate the rBA of the commercial formulation of PF-04965842 (Test formulation 1) and the variant formulation with slower dissolution (Test formulation 2) compared to the Phase 3 formulation (Reference formulation), to demonstrate the BE of the commercial formulation relative to the Phase 3 formulation, and to estimate the effect of food on the rBA of the commercial formulation after a single 200 mg oral dose.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A sequence 1<br> | Drug: P3-Fast<br>* 200 mg (2 × 100 mg) PF-04965842 Phase 3 tablet formulation under fasted conditions<br>Drug: Comm-Fast<br>* 200 mg PF-04965842 commercial tablet formulation under fasted conditions<br>Drug: Vari-Fast<br>* 200 mg PF-04965842 variant tablet formulation with slower dissolution under fasted conditions<br>Drug: Comm-Fed<br>* 200 mg PF-04965842 commercial tablet formulation under fed conditions<br>|
| Experimental: Part A sequence 2<br> | Drug: P3-Fast<br>* 200 mg (2 × 100 mg) PF-04965842 Phase 3 tablet formulation under fasted conditions<br>Drug: Comm-Fast<br>* 200 mg PF-04965842 commercial tablet formulation under fasted conditions<br>Drug: Vari-Fast<br>* 200 mg PF-04965842 variant tablet formulation with slower dissolution under fasted conditions<br>Drug: Comm-Fed<br>* 200 mg PF-04965842 commercial tablet formulation under fed conditions<br>|
| Experimental: Part B sequence 1<br> | Drug: P3-Fast<br>* 200 mg (2 × 100 mg) PF-04965842 Phase 3 tablet formulation under fasted conditions<br>Drug: Comm-Fast<br>* 200 mg PF-04965842 commercial tablet formulation under fasted conditions<br>|
| Experimental: Part B sequence 2<br> | Drug: P3-Fast<br>* 200 mg (2 × 100 mg) PF-04965842 Phase 3 tablet formulation under fasted conditions<br>Drug: Comm-Fast<br>* 200 mg PF-04965842 commercial tablet formulation under fasted conditions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma PF-04965842 PK parameters | AUCinf | hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 
| Plasma PF-04965842 PK parameters | Cmax | hour 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of subjects with treatment-emergent adverse event |  | baseline until Period 4 study day 35 | 
| number of subjects with significant change from baseline in Supine Blood pressure, pulse rate and oral temperature | The actual and the change from baseline values will be summarized by treatment. These data will be listed and out of range values will be summarized | baseline until Period 4 study day 3 | 
| number of subjects with significant Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR | Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR interval, and QRS complex will be summarized by treatment and time. The number (%) of participants with maximum postdose QTc values and maximum increases from baseline in the following categories will be tabulated by treatment | baseline until Period 4 study day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1 Bioequivalence Study, Healthy Participants, Estimation of the Effect of Food, Relative Bioavailability