A Study To Evaluate The Effect Of Itraconazole On Pharmacokinetics Of PF-06463922 In Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: PF-06463922; Drug: Itraconazole

• Registration Number: NCT02838264
• Lead Sponsor: Pfizer

Brief Summary

The purpose of this study is to estimate the effect of itraconazole on the single dose pharmacokinetics of PF-06463922 in healthy volunteers in the fasted state.

Detailed Description

This will be a Phase 1, open-label, 2-period, fixed-sequence, crossover study to investigate the effect of the strong CYP3A inhibitor itraconazole on PF-06463922 PK in approximately 16 healthy volunteers. The study will consist of potentially up to 6 treatments: single dose of PF-06463922 50, 75 or 100 mg and PF-06463922 50, 75 or 100 mg in combination with multiple dose itraconazole.

Study Timeline

• Study First Submitted: 2016-07-17
• Study First Submitted QC: 2016-07-17
• Study First Posted: 2016-07-20
• Study Start: 2016-08-16
• Primary Completion: 2017-03-31
• Status Verified: 2017-05
• Study Completion: 2017-05-03
• Last Update Submitted: 2017-05-12
• Last Update Posted: 2017-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Healthy female subjects of non childbearing potential and/or male subjects, who at the time of screening, are 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

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Any condition possibly affecting drug absorption.
• A positive urine drug test.
• History of HIV, Hep B or Hep C.
• History of regular alcohol consumption.
• Screening supine 12 lead ECG demonstrating PR interval >180 msec, QTc >450 msec or a QRS interval >120 msec.
• Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary: Use this criterion to describe any laboratory parameters that are not acceptable for the study. Examples included below:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >1.0 × upper limit of normal (ULN);
• Total bilirubin level >1.0 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is <= ULN.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 2	PF-06463922	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.
Cohort 4	PF-06463922	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive the highest safe dose (mg) of PF-06463922 as a single-dose Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.
Cohort 1	PF-06463922	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.
Cohort 3	PF-06463922	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.
Cohort 1	Itraconazole	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.
Cohort 2	Itraconazole	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.
Cohort 3	Itraconazole	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive PF-06463922 Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.
Cohort 4	Itraconazole	All subjects in this cohort will receive the same dose of PF-06463922 in both periods. Subjects will receive the highest safe dose (mg) of PF-06463922 as a single-dose Alone in Period 1 followed by PF-06463922 with Itraconazole in Period 2.

Primary Outcome Measures

Name	Time	Method
AUCinf for PF-06463922	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Area under the plasma concentration-time profile from time zero extrapolated to infinite time
Cmax for PF-06463922	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Maximum plasma concentration

Secondary Outcome Measures

Name	Time	Method
CL/F for PF-06463922	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Apparent clearance
Vz/F for PF-06463922	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Apparent volume of distribution
t1/2 for PF-06463922	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Terminal plasma elimination half-life
AUCinf for any potential PF-06463922 metabolite if necessary	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Area under the plasma concentration-time profile from time zero extrapolated to infinite time
AUClast for PF-06463922	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)
Cmax for any potential PF-06463922 metabolite if appropriate	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Maximum plasma concentration
Tmax for any potential PF-06463922 metabolite if appropriate	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Time to Cmax
t1/2 for any potential metabolite of PF-06463922 if appropriate	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Terminal plasma elimination half-life
Tmax for PF-06463922	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and upto 168 hours post-dose.	Time to Cmax
MRAUClast for any potential PF-06463922 metabolite if appropriate	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	metabolite to parent ratio for AUClast
MRAUCinf for any potential PF-06463922 metabolite if appropriate	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	metabolite to parent ratio for AUCinf
PR interval after PF-06463922 alone and after increased exposure of PF 06463922 (due to concomitant itraconzole administration).	Within 24 hours after single dose administration of PF-06463922 alone and in combination with itraconazole.	Change in PR interval from baseline after administration of PF-06463922 single dose as assessed by ECG.
AUClast for any potential PF-06463922 metabolite if necessary	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)
MRCmax for any potential PF-06463922 metabolite if appropriate	PF-06463922 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and up to 168 hours post-dose.	metabolite to parent ratio for Cmax

Trial Locations

Locations (1)

Pfizer Clinical Research Unit; 🇧🇪 Brussels, Belgium