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Drug Drug Interaction Study Of Crizotinib With Esomeprazole.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01549574
First received: February 25, 2012
Last updated: June 1, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: crizotinib
Drug: esomeprazole
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Plasma AUCinf [area under the plasma concentration-time profile from time 0 to infinite time] for crizotinib [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma Cmax [maximum observed concentration] for crizotinib [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma AUClast [area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration] for crizotinib [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma Tmax [time for maximum observed concentration] for crizotinib [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma t1/2 [terminal half-life] for crizotinib [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma CL/F [apparent oral clearance] for crizotinib [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma Vz/F [apparent volume of distribution] for crizotinib [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma AUClast for metabolite (PF-06260182) if appropriate [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • crizotinib/metabolite AUClast ratio if appropriate [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma AUCinf for metabolite (PF-06260182) if appropriate [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • crizotinib/metabolite AUCinf ratio if appropriate [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma Cmax for metabolite (PF-06260182) if appropriate [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • crizotinib/metabolite Cmax ratio if appropriate [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma Tmax for metabolite (PF-06260182) if appropriate [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: May 2012
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01549574

Locations
Belgium
Pfizer Investigational Site
Bruxelles, Belgium, B-1070
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01549574     History of Changes
Other Study ID Numbers: A8081035
Study First Received: February 25, 2012
Last Updated: June 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
crizotinib
pharmacokinetics
esomeprazole
proton pump inhibitor
drug drug interaction
healthy volunteers

Additional relevant MeSH terms:
Crizotinib
Esomeprazole
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014