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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: crizotinib; Drug: rifampin

• Registration Number: NCT01147055
• Lead Sponsor: Pfizer

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-06-16
• Study First Submitted QC: 2010-06-16
• Study First Posted: 2010-06-22
• Study Start: 2010-07
• Primary Completion: 2010-10
• Study Completion: 2010-10
• Results First Submitted: 2011-09-12
• Results First Submitted QC: 2011-09-12
• Status Verified: 2011-10
• Results First Posted: 2011-10-19
• Last Update Submitted: 2011-10-20
• Last Update Posted: 2011-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	crizotinib	There should be at least 14-day washout period between treatment A and B.
1	rifampin	There should be at least 14-day washout period between treatment A and B.

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	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)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	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)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Plasma Decay Half-Life (t1/2)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Apparent Oral Clearance (CL/F)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose CL/F is influenced by the fraction of the dose absorbed.
Apparent Volume of Distribution (Vz/F)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	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)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	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)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) of crizotinib metabolite (PF-06260182). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Metabolite to Parent Ratio Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	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 Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC (0 - ∞)]	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	Molar ratio of metabolite to parent area under the curve from time zero to extrapolated infinite time \[MRAUC (0-∞)\].
Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax)	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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2	Metabolite to parent molar ratio of maximum observed plasma concentration (MRCmax).

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇺🇸 South Miami, Florida, United States