Clinical trial NCT01549574: Drug Drug Interaction Study Of Crizotinib With Esomeprazole.
Official title: A Phase 1, Open Label, Single Dose, Randomized, Cross-Over Study To Estimate The Effect Of Esomeprazole On The Pharmacokinetics Of Crizotinib In Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: crizotinib
pharmacokinetics
esomeprazole
proton pump inhibitor
drug drug interaction
healthy volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-03-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is an open-label, randomized, cross-over, single dose study in healthy volunteers to evaluate the potential effect of esomeprazole, a proton pump inhibitor, on the pharmacokinetics of crizotinib. Each subject enrolled will receive two single oral doses of crioztinib with or without esomeprazole separated by a washout period of at least 14 days.


Eligibility criteria: Inclusion Criteria:

* Healthy male and/or female of non childbearing potential subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG or clinical laboratory tests).
* Body Mass Index (BMI) of 17.5 to 30.5 kg/m\^2; 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 time of dosing).
* Any condition possibly affecting drug absorption (eg, gastrectomy).
* A positive urine drug screen.
* History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
* Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half lives preceding the first dose of study medication.
* Screening supine blood pressure \>= 140 mm Hg (systolic) or \>=90 mm Hg (diastolic), on a single measurement (confirmed by a single repeat, if necessary) following at least 5 minutes of rest.
* Screening 12 lead ECG demonstrating QTc \>450 or a QRS interval \>120 msec at Screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
* Pregnant or nursing females; females of childbearing potential, including those with tubal ligation.
* Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of =\< 1 g/day. Limited use of non prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
* A positive serology for Hepatitis B or Hepatitis C.

Primary outcomes:
measure: Plasma AUCinf [area under the plasma concentration-time profile from time 0 to infinite time] for crizotinib
timeFrame: 2 months
measure: Plasma Cmax [maximum observed concentration] for crizotinib
timeFrame: 2 months
Secondary outcomes:
measure: Plasma AUClast [area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration] for crizotinib
timeFrame: 2 months
measure: Plasma Tmax [time for maximum observed concentration] for crizotinib
timeFrame: 2 months
measure: Plasma t1/2 [terminal half-life] for crizotinib
timeFrame: 2 months
measure: Plasma CL/F [apparent oral clearance] for crizotinib
timeFrame: 2 months
measure: Plasma Vz/F [apparent volume of distribution] for crizotinib
timeFrame: 2 months
measure: Plasma AUClast for metabolite (PF-06260182) if appropriate
timeFrame: 2 months
measure: crizotinib/metabolite AUClast ratio if appropriate
timeFrame: 2 months
measure: Plasma AUCinf for metabolite (PF-06260182) if appropriate
timeFrame: 2 months
measure: crizotinib/metabolite AUCinf ratio if appropriate
timeFrame: 2 months
measure: Plasma Cmax for metabolite (PF-06260182) if appropriate
timeFrame: 2 months
measure: crizotinib/metabolite Cmax ratio if appropriate
timeFrame: 2 months
measure: Plasma Tmax for metabolite (PF-06260182) if appropriate
timeFrame: 2 months
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Xu H, O'Gorman M, Matschke K, Boutros T, Brega N, Tan W, Bello A. Evaluation of Proton Pump Inhibitor Esomeprazole on Crizotinib Pharmacokinetics in Healthy Participants. Clin Pharmacol Drug Dev. 2022 Jan;11(1):34-42. doi: 10.1002/cpdd.1032. Epub 2021 Nov 26.