A Study To Evaluate The Effect Of Itraconazole On Pharmacokinetics Of PF-06463922 In Healthy Volunteers
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 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. |
Drug: PF-06463922
Single oral dose of PF-06463922 50 mg on Day 1 of Period 1 and Day 5 of Period 2
Other Names:
Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Names:
|
| Experimental: Cohort 2 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. |
Drug: PF-06463922
Single oral dose of PF-06463922 75 mg on Day 1 of Period 1 and Day 5 of Period 2
Other Names:
Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Names:
|
| Experimental: Cohort 3 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. |
Drug: PF-06463922
Single oral dose of PF-06463922 100 mg on Day 1 of Period 1 and Day 5 of Period 2
Other Names:
Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Names:
|
| Experimental: Cohort 4 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. |
Drug: PF-06463922
Highest safe single oral dose (mg) of PF-06463922 identified in the previous cohorts will be administered on Day 1 of Period 1 and Day 5 of Period 2
Other Names:
Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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)
- 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
- 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
- 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
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Clinical Research Unit | Brussels | Belgium | B-1070 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- B7461012
- 2016-002386-57
- ITRACONAZOLE DDI STUDY