A Study To Estimate The Effects Of Itraconazole On Pharmacokinetics Of Pf-06649751 In Healthy Adult Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the impact of CYP3A4 inhibitor, itraconazole, on plasma concentration of PF-06649751 in healthy subjects

Official Title
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A Phase 1, Open-label, Fixed-sequence Study To Estimate The Effects Of Multiple-dose Administration Of Itraconazole On The Steady-state Pharmacokinetics Of Pf-06649751 In Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF06649751, Itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study: Healthy female subjects of nonchildbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Female subjects of nonchildbearing potential must meet at least 1 of the following criteria: Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 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). Unwilling or unable to comply with the Lifestyle Guidelines described in the protocol. Unwilling or unable to comply with the Lifestyle Requirements described in this protocol Subjects who had a history of allergy or intolerance to azole antifungal drugs

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br> | Drug: PF06649751, Itraconazole<br>* PF-06649751 0.25 mg on Days 1,2,3 PF-06649751 0.5 mg on Days 4,5,6 PF-06649751 1 mg on Days 7 to Day 25 Itracoanzole 200 mg on Days 12 to Day 25<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PF-06649751 and PF-06752844 steady state Cmax | Maximum Observed Plasma Concentration | Day 11 and Day 25 | 
| PF-06649751 and PF-06752844 steady state AUC24 | Area Under the Curve From Time Zero to the end of the dosing period | Days 11 and Day 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS assess whether participant experience the following: completed suicide (1), suicide attempt (2) (response YES on actual attempt), preparatory acts toward imminent suicidal behavior (3) (yes on preparatory acts or behavior), suicidal ideation (4) (yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific pan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (yes on Has subject engaged in non-suicidal self-injurious behavior). | Day 0 | 
| Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS assess whether participant experience the following: completed suicide (1), suicide attempt (2) (response YES on actual attempt), preparatory acts toward imminent suicidal behavior (3) (yes on preparatory acts or behavior), suicidal ideation (4) (yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific pan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (yes on Has subject engaged in non-suicidal self-injurious behavior). | Day 7 | 
| Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS assess whether participant experience the following: completed suicide (1), suicide attempt (2) (response YES on actual attempt), preparatory acts toward imminent suicidal behavior (3) (yes on preparatory acts or behavior), suicidal ideation (4) (yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific pan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (yes on Has subject engaged in non-suicidal self-injurious behavior). | Day 14 | 
| Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS assess whether participant experience the following: completed suicide (1), suicide attempt (2) (response YES on actual attempt), preparatory acts toward imminent suicidal behavior (3) (yes on preparatory acts or behavior), suicidal ideation (4) (yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific pan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (yes on Has subject engaged in non-suicidal self-injurious behavior). | Day 21 | 
| Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS assess whether participant experience the following: completed suicide (1), suicide attempt (2) (response YES on actual attempt), preparatory acts toward imminent suicidal behavior (3) (yes on preparatory acts or behavior), suicidal ideation (4) (yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific pan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (yes on Has subject engaged in non-suicidal self-injurious behavior). | Day 26 | 
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Y days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug X was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. | Day 1 to Day 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug drug interaction, CYP3A4, itraconazole