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

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ClinicalTrials.gov Identifier: NCT02838264
Recruitment Status : Completed
First Posted : July 20, 2016
Last Update Posted : May 15, 2017
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Healthy Drug: PF-06463922 Drug: Itraconazole 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Phase 1, Open-label, Fixed Sequence, 2-period Study To Investigate The Effect Of Multiple Doses Of Itraconazole On The Pharmacokinetics Of Single Dose Pf-06463922 In Healthy Volunteers In The Fasted Condition
Actual Study Start Date : August 16, 2016
Actual Primary Completion Date : March 31, 2017
Actual Study Completion Date : May 3, 2017

Resource links provided by the National Library of Medicine


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 Name: Lorlatinib

Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Name: Sporanox

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 Name: Lorlatinib

Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Name: Sporanox

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 Name: Lorlatinib

Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Name: Sporanox

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 Name: Lorlatinib

Drug: Itraconazole
200 mg oral dose of itraconazole on Days 1 to 11 during Period 2
Other Name: Sporanox




Primary Outcome Measures :
  1. AUCinf for PF-06463922 [ Time Frame: 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

  2. Cmax for PF-06463922 [ Time Frame: 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 :
  1. AUClast for PF-06463922 [ Time Frame: 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)

  2. Tmax for PF-06463922 [ Time Frame: 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

  3. t1/2 for PF-06463922 [ Time Frame: 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

  4. CL/F for PF-06463922 [ Time Frame: 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

  5. Vz/F for PF-06463922 [ Time Frame: 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

  6. AUCinf for any potential PF-06463922 metabolite if necessary [ Time Frame: 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

  7. AUClast for any potential PF-06463922 metabolite if necessary [ Time Frame: 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)

  8. Cmax for any potential PF-06463922 metabolite if appropriate [ Time Frame: 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

  9. Tmax for any potential PF-06463922 metabolite if appropriate [ Time Frame: 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

  10. t1/2 for any potential metabolite of PF-06463922 if appropriate [ Time Frame: 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

  11. MRCmax for any potential PF-06463922 metabolite if appropriate [ Time Frame: 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

  12. MRAUClast for any potential PF-06463922 metabolite if appropriate [ Time Frame: 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

  13. MRAUCinf for any potential PF-06463922 metabolite if appropriate [ Time Frame: 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

  14. PR interval after PF-06463922 alone and after increased exposure of PF 06463922 (due to concomitant itraconzole administration). [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02838264


Locations
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Belgium
Pfizer Clinical Research Unit
Brussels, Belgium, B-1070
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02838264     History of Changes
Other Study ID Numbers: B7461012
2016-002386-57 ( EudraCT Number )
ITRACONAZOLE DDI STUDY ( Other Identifier: Alias Study Number )
First Posted: July 20, 2016    Key Record Dates
Last Update Posted: May 15, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors