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

Pfizer15 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

crizotinibDRUG

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.

ketoconazoleDRUG

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.

crizotinibDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Pfizer Investigational Site

South Miami, Florida, United States

Outcomes

Primary Outcomes

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)]

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-∞).

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

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

Secondary Outcomes

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

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)

Plasma Decay Half-Life (t1/2)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Data from ClinicalTrials.gov

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Apparent Oral Clearance (CL/F)

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)

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)

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)

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)

Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)

Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast)

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-∞)]

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)

Metabolite to parent molar ratio of maximum observed plasma concentration (Cmax).