Estimation Of Effect Of Ketoconazole On Pharmacokinetics Of Crizotinib In Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01149785
First received: June 21, 2010
Last updated: October 20, 2011
Last verified: October 2011

June 21, 2010
October 20, 2011
July 2010
September 2010   (final data collection date for primary outcome measure)
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
Plasma AUCinf and Cmax for crizotinib given alone or with ketoconazole [ Time Frame: 2 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01149785 on ClinicalTrials.gov Archive Site
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Apparent Oral Clearance (CL/F) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
  • Apparent Volume of Distribution (Vz/F) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of crizotinib metabolite (PF-06260182).
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Crizotinib Metabolite (PF-06260182) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞) of crizotinib metabolite (PF-06260182).
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
  • Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Molar ratio of metabolite to parent area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (MRAUClast).
  • Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC(0-∞)] [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Molar ratio of metabolite to parent area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞) [MRAUC(0-∞)].
  • Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax) [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ] [ Designated as safety issue: No ]
    Metabolite to parent molar ratio of maximum observed plasma concentration (Cmax).
  • Plasma AUClast, Tmax, t1/2, CL/F, and Vz/F for crizotinib given alone or with ketoconazole. [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Plasma AUClast, AUCinf, Tmax, and Cmax for crizotinib metabolite(s) and crizotinib/metabolite(s) ratio given alone or with ketoconazole if appropriate. [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Safety laboratory tests, physical examination, ECG, concomitant medication and adverse event monitoring. [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Estimation Of Effect Of Ketoconazole On Pharmacokinetics Of Crizotinib In Healthy Volunteers
A Phase 1, Fixed Sequence, Cross-Over Study To Estimate The Effect Of Multiple Doses Of Ketoconazole On The Single Dose Pharmacokinetics Of Crizotinib (PF-02341066) In Healthy Volunteers

The purpose of this study is to estimate the effect of multiple doses of ketoconazole on the single dose pharmacokinetics of crizotinib in healthy volunteers.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Healthy
  • Drug: crizotinib
    Treatment A: a single 150-mg dose of crizotinib will be administered in the fasted state on Day 1 as 1 × 50-mg and 1 × 100-mg Immediate Release Tablets.
  • Drug: ketoconazole
    Treatment B: 200 mg twice a day (approximately 12 hrs apart) doses of ketoconazole will be administered orally on an empty stomach from Day 1 to Day 16.
  • Drug: crizotinib
    Treatment B: A single 150-mg dose of crizotinib will be administered in the fasted state on Day 4 as 1 × 50-mg and 1 × 100-mg Immediate Release Tablets.
Experimental: 1
There should be at least 14-day washout period between treatment A and B.
Interventions:
  • Drug: crizotinib
  • Drug: ketoconazole
  • Drug: crizotinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
September 2010
September 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy male and/or female of non-child bearing 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 and 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:

  • Subjects with evidence of disease, conditions affecting drug absorption, treatment with other investigational drug within 30 days, history of regular alcohol consumption, and use of prescription , nonprescription drugs and dietary supplement within 7 days, and blood donation of 500 mL within 56 days.
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01149785
A8081015
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP