Drug Drug Interaction Study Of Crizotinib With Esomeprazole.

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: crizotinib; Drug: esomeprazole

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, B-1070
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: crizotinib/crizotinib+esomeprazole crossover; Each subject in this study will receive two treatments (A and B) separated by at least 14 days of washout period. Treatment A is a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule. Treatment B consists of 40 mg daily esomeprazole dose from Day 1 to Day 5 and a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule on Day 5.

Drug: crizotinib; Each subject in Treatment A will receive a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule on Day 1 and each subject in Treatment B will receive a 250 mg single oral dose of crizotinib administered in a fasted state as 1x 250 mg Formulated Capsule on Day 5; Drug: esomeprazole; Each subject in Treatment B will receive 40 mg daily dose of esomeprazole from Day 1 to Day 5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma AUCinf [area under the plasma concentration-time profile from time 0 to infinite time] for crizotinib	2 months
Plasma Cmax [maximum observed concentration] for crizotinib	2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma AUClast [area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration] for crizotinib	2 months
Plasma Tmax [time for maximum observed concentration] for crizotinib	2 months
Plasma t1/2 [terminal half-life] for crizotinib	2 months
Plasma CL/F [apparent oral clearance] for crizotinib	2 months
Plasma Vz/F [apparent volume of distribution] for crizotinib	2 months
Plasma AUClast for metabolite (PF-06260182) if appropriate	2 months
crizotinib/metabolite AUClast ratio if appropriate	2 months
Plasma AUCinf for metabolite (PF-06260182) if appropriate	2 months
crizotinib/metabolite AUCinf ratio if appropriate	2 months
Plasma Cmax for metabolite (PF-06260182) if appropriate	2 months
crizotinib/metabolite Cmax ratio if appropriate	2 months
Plasma Tmax for metabolite (PF-06260182) if appropriate	2 months

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: February 25, 2012
• First Submitted That Met QC Criteria: March 8, 2012
• First Posted (Estimate): March 9, 2012

Study Record Updates

• Last Update Posted (Estimate): June 5, 2012
• Last Update Submitted That Met QC Criteria: June 1, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy volunteers; proton pump inhibitor; esomeprazole; crizotinib; drug drug interaction
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Protein Kinase Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole; Crizotinib
• Other Study ID Numbers: A8081035