Drug Drug Interaction Study Evaluating the Effect of Fluvoxamine or Fluconazole on PK and Safety of PF-04965842.

Study Overview
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Brief Summary
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A Phase 1, Open Label, Parallel-Cohort, Randomized, Fixed Sequence Study To Evaluate The Pharmacokinetic Drug Drug Interaction Between PF-04965842 and Fkuvoxamine (cohort 1) or Fluconazole (Cohort 2) in healthy subjects.

Detailed Description
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A phase 1 study to evaluate the effect of fluvoxamine (a strong CYP2C19 and moderate CYP3A inhibitor) or fluconazole (a strong CYP2C19, moderate CYP2C9 and CYP3A inhibitor) on the pharmacokinetics, safety and tolerability of PF-04965842 in healthy subjects. This study will be a Phase 1, open label, randomized, fixed-sequence, parallel-cohort study drug-drug interaction study. The study includes 2 periods: In Period 1: all subjects will receive one single oral dose of 100 mg PF 04965842 tablet. (Treatment A). PK will be evaluated in the first 72 hours post adminstration of PF 04965842. In Period 2: Cohort 1: subjects will receive fluvoxamine (immediate release tablet 50 mg) once daily for 9 consecutive days; on Day 8, subjects will receive a single oral dose of 100 mg PF 04965842 approximately 3 hours after fluvoxamine administration. (Treatment B). PK will be evaluated in the first 72 hours post administration of PF 04965842. Cohort 2: subjects will receive fluconazole capsule(s) once daily for 7 consecutive days (400 mg on Day 1 and 200 mg on Day 2-7 in Period 2); on Day 5, subjects will receive a single oral dose of 100 mg PF 04965842 approximately 1 hour after fluconazole administration. (Treatment C). PK will be evaluated in the first 72 hours post administration of PF 04965842.

Official Title
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A PHASE 1, OPEN-LABEL, RANDOMIZED, FIXED-SEQUENCE, PARALLEL-COHORT STUDY TO ESTIMATE THE EFFECT OF FLUVOXAMINE OR FLUCONAZOLE, ON THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF A SINGLE DOSE OF PF-04965842 IN HEALTHY SUBJECTS

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: Period 1 - Day 1: PF-04965842 administered
* Drug: Period 2: Cohort 1: Fluvoxamine & PF-04965842
* Drug: Period 2: Cohort 2: Fluconazole & PF-04965842


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects. Body mass index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight >50 kg (110 lb). Exclusion Criteria: Evidence or history of hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease. Evidence or history of clinically significant dermatological condition (eg, contact dermatitis or psoriasis) or visible rash present during physical examination. History of hypersensitivity to or intolerance of fluvoxamine and/or fluconazole. Any condition possibly affecting drug absorption. A positive urine drug test. Screening supine systolic BP <90 mm Hg or 140 mm Hg following at least 5 minutes of supine rest OR Screening supine diastolic BP <50 mm Hg or 90 mm Hg following at least 5 minutes of supine rest. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception.

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04965842<br>investigational drug | Drug: Period 1 - Day 1: PF-04965842 administered<br>* Period 1: Single administration of 100 mg PF 04965842.<br>* Other names: Single administration of PF-04965842 in Period 1.;Drug: Period 2: Cohort 1: Fluvoxamine & PF-04965842<br>* Cohort 1: Period 2: Administration of fluvoxamine from Day 1 to Day 9 and PF-04965842 on Day 8.<br>* Other names: 9-day administration of Fluvoxamine and single administration of PF-04965842 on day 8.;Drug: Period 2: Cohort 2: Fluconazole & PF-04965842<br>* Cohort 2: Period 2: Administration of fluconazole from Day 1 to Day 7 and PF-04965842 on Day 5.<br>* Other names: 7-day administration of fluconazole and single administration of PF-04965842 on day 5.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Cmax for PF 04965842 | Maximum Observed Plasma Concentration (Cmax) for PF 04965842 | First 72 hours post PF-04965842 administration in Period 1 and Period 2 | 
| AUCinf for PF-04965842 | Area Under the Curve From Time Zero to Extrapolated Infinite Time for PF 04965842 (AUCinf) | First 72 hours post PF-04965842 administration in Period 1 and Period 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Adverse events (AEs) | Number of subjects with Adverse events (AEs) | Screening up to 28 Days after the Last Dose of PF 04965842 | 
| Number of subjects with laboratory tests findings of potential clinical importance | Number of subjects with laboratory tests findings of potential clinical importance | Screening up to 7-14 Days after the Last Dose of PF 04965842 in Period 2 | 
| Number of Subjects with clinically significant abnormal Vital Signs | Number of Subjects with clinically significant abnormal Vital Signs | Screening up to 7-14 Days after the Last Dose of PF 04965842 in Period 2 | 
| Number of Subjects with Electrocardiograms (ECGs) findings of potential clinical importance | Number of Subjects with Electrocardiograms (ECGs) findings of potential clinical importance | Screening up to 7-14 Days after the Last Dose of PF 04965842 in Period 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic dermatitis