Effect of Multiple Doses of Itraconazole on the Pharmacokinetics of a Single-Dose of PF-06651600 in Healthy Participants

Study Overview
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Brief Summary
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This study will estimate the impact of a strong CYP3A4 inhibitor (itraconazole) on the pharmacokinetics of an investigational product (PF-06651600) in healthy adult participants. This is an open-label, fixed sequence two period study with healthy participants that will receive a single dose of PF-06651600 alone and co-administered with multiple doses of itraconazole at a single center. Participants will be screened within 28 days of the first dose of the investigational products and if entry criteria are met, the participant will report to the clinic on the day before the Day 1 visit. On Day 1 of Period 1, each participant will receive a 30 mg dose of PF-06651600 and PK samples will be collected for 48 hours. In Period 2, participants will receive itraconazole solution from Day 1-5. On Day 4 of Period 2 the participant will receive 30 mg of PF-06651600 with the itraconazole. PK samples will be collected up to 48 hours after the PF-06651600 dose. Participants will be confined for a total of 9 days in the clinic. The participant will be followed up by phone contact.

Official Title
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A PHASE 1, OPEN-LABEL, FIXED SEQUENCE 2-PERIOD STUDY TO INVESTIGATE THE EFFECT OF MULTIPLE DOSES OF ITRACONAZOLE ON THE PHARMACOKINETICS OF A SINGLE DOSE OF PF-06651600 IN HEALTHY PARTICIPANTS

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: PF-06651600 10 mg tablets
* Drug: Itraconazole Solution 200 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg. Exclusion Criteria: Evidence of congestive heart failure or history of congestive heart failure or any of the following: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident including transient ischemic attack or pulmonary embolus. Known hypersensitivity to itraconazole or it excipients or to other azole antifungals. Infection with Hepatitis B, C or HIV Known present or history of malignancy other than a successfully 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06651600 treatment arm<br>This arm includes two treatment periods. Period 1-Single oral dose of PF-06651600 30 mg as tablets on Day 1 followed by Period 2 in which itraconazole 200 mg (oral solution) is given for 5 days. On Day 4 of Period 2, a single oral dose of PF-06651600 30 mg is given with itraconazole | Drug: PF-06651600 10 mg tablets<br>* On Day 1 in Period 1, a single oral dose of 30 mg (3 x 10 mg tablets) will be administered. On Day 4 of Period 2, a single oral dose of 30 mg (3 x 10 mg tablets) will be administered after itraconazole.<br>Drug: Itraconazole Solution 200 mg<br>* Itraconazole 200 mg will be administered as 20 mL (10 mg/mL) oral solution once daily on Days 1-5 in Period 2. On Day 4 of Period 2, co-administration of itraconazole 200 mg and PF-06651600 30 mg will occur. Itraconazole will be administered first followed by PF-06651600 tablets.<br>* Other names: Sporanox Oral Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single dose Area under the curve from time zero to infinity [AUC (0-inf)] of PF-06651600 | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinity. | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 and 48 hours | 
| Maximum observed plasma concentration of PF-06651600 | Peak concentration of PF-06651600 | 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 and 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (AEs) |  | Baseline up to 35 days | 
| Number of adverse events leading to discontinuation |  | Baseline up to 35 days | 
| Number of participants with clinically significant change in vital signs from Baseline |  | Baseline to Day 9 | 
| Number of participants with clinically significant abnormalities in clinical laboratory values |  | Baseline to Day 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PF-06651600, Itraconazole, CYP3A4, Drug-Drug Interaction