Healthy
Conditions
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.
Interventions
DRUGPF-06463922
Single oral dose of PF-06463922 50 mg on Day 1 of Period 1 and Day 5 of Period 2
DRUGItraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Sponsors
Pfizer
Study design
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 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) |
| 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 |
| 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) |
| 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 |
| 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 |
| 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. |
| 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 |
| 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 |
Countries
Belgium
Outcome results
None listed