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

NCT02838264 | Completed Phase 1

• 3 other identifiers: B74610122016-002386-57ITRACONAZOLE DDI STUDY
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• AUCinf for PF-06463922

  Area under the plasma concentration-time profile from time zero extrapolated to infinite time

  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.

• Cmax for PF-06463922

  Maximum plasma concentration

  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.

Secondary Outcomes (14)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (4)

Cohort 1

EXPERIMENTAL

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; Drug: Itraconazole

Cohort 2

EXPERIMENTAL

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; Drug: Itraconazole

Cohort 3

EXPERIMENTAL

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; Drug: Itraconazole

Cohort 4

EXPERIMENTAL

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; Drug: Itraconazole

Interventions

PF-06463922 DRUG

Single oral dose of PF-06463922 50 mg on Day 1 of Period 1 and Day 5 of Period 2

Also known as: Lorlatinib

Cohort 1

Itraconazole DRUG

200 mg oral dose of itraconazole on Days 1 to 11 during Period 2

Also known as: Sporanox

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Location

Related Publications (1)

• Patel M, Chen J, McGrory S, O'Gorman M, Nepal S, Ginman K, Pithavala YK. The effect of itraconazole on the pharmacokinetics of lorlatinib: results of a phase I, open-label, crossover study in healthy participants. Invest New Drugs. 2020 Feb;38(1):131-139. doi: 10.1007/s10637-019-00872-7. Epub 2019 Nov 14.

  PMID: 31728714 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

lorlatinib; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: BASIC SCIENCE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2016
• First Posted: July 20, 2016
• Study Start: August 16, 2016
• Primary Completion: March 31, 2017
• Study Completion: May 3, 2017
• Last Updated: May 15, 2017

Record last verified: 2017-05

Locations

BE (1)