A Study to Evaluate the Effects of Food and Esomeprazole on the Pharmacokinetics of Crizotinib in a Coated Microsphere Formulation.

NCT03137134 | Completed Phase 1 FDA Drug

• 2 other identifiers: A8081066PPI/FE
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study will estimate the effect of food and the proton pump inhibitor, esomeprazole on the pharmacokinetics of crizotinib in a coated microsphere formulation.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

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

  Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)

  AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

• Maximum Observed Plasma Concentration (Cmax)

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

Secondary Outcomes (8)

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

• Time of last observed concentration (Tlast)

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

• Plasma Decay Half-Life (t1/2)

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

• Apparent Oral Clearance (CL/F)

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

• Apparent Volume of Distribution (Vz/F)

  Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose

Study Arms (5)

Treatment A

ACTIVE COMPARATOR

(reference) Crizotinib cMS 300 mg in fasted state

Drug: Crizotinib

Treatment B

EXPERIMENTAL

(test) Crizotinib cMS 300 mg in fed state

Drug: Crizotinib

Treatment C

EXPERIMENTAL

(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg in fasted state

Drug: Crizotinib; Drug: Esomeprazole

Treatment D

EXPERIMENTAL

(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg with apple sauce.

Drug: Crizotinib; Drug: Esomeprazole

Treatment E

EXPERIMENTAL

(test) 5 days of esomeprazole 40 mg followed by crizotinib cMS 300 mg with orange juice

Drug: Crizotinib; Drug: Esomeprazole

Interventions

Crizotinib DRUG

Crizotinib in a coated microsphere formulation

Treatment A; Treatment B; Treatment C; Treatment D; Treatment E

Esomeprazole DRUG

Proton pump inhibitor, esomeprazole

Treatment C; Treatment D; Treatment E

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects and female subjects of nonchildbearing potential between 18 and 55 years old.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug test.
• Subjects who currently smoke.
• History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (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 before screening.
• Subjects with history of known sensitivity to esomeprazole or substituted benzimidazoles.
• Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study drug.
• Screening supine BP greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic), following at least 5 minutes of supine rest.
• Screening supine 12-lead triplicate ECG demonstrating a corrected time from the beginning of the Q wave to the end of the T wave corresponding to electrical systole (QTc) interval \>450 msec or a QRS complex \>120 msec.
• Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:
• Aspartate aminotransferase (AST) or ALT level greater than or equal to 1.5 × upper limit of normal (ULN);
• Total bilirubin (TBili) level greater than or equal to 1.5 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is less than or equal to ULN.
• Male subjects who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of investigational product.
• 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 IP.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

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

MeSH Terms

Interventions

Crizotinib; Esomeprazole

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines; Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 2, 2017
• Study Start: June 20, 2017
• Primary Completion: September 19, 2017
• Study Completion: October 17, 2017
• Last Updated: October 31, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)