Bioequivalence Study for Crizotinib Encapsulated Microsphere Formulation (eMS)

NCT04856293 | Completed Phase 1 FDA Drug

• 1 other identifier: A8081074
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Bioequivalence study to evaluate the pharmacokinetics of a new crizotinib encapsulated microsphere (eMS) formulation

Conditions

Healthy Participants

Keywords

Crizotinib; Encapsulated Microsphere Formulation; Healthy adult participants

Outcome Measures

Primary Outcomes (6)

• Plasma AUCinf after administration of the FC formulation

  Area under the plasma concentration-time profile from time zero extrapolated to infinite time Method of Determination: Linear-log trapezoidal method

  Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3)

• Plasma Cmax after administration of the FC formulation

  Maximum plasma concentration Method of Determination: Observed directly from the data

  Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3)

• Plasma AUClast after administration of the FC formulation

  Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (Clast) Method of Determination: AUClast + (Clast/kel) Where Clast is the predicted plasma concentration at the last quantifiable time point and kel is the elimination rate constant estimated from the loglinear regression analysis.

  Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3)

• Plasma AUCinf after administration of the unencapsulated eMS formulation

  Area under the plasma concentration-time profile from time zero extrapolated to infinite time Method of Determination: Linear-log trapezoidal method

  Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3)

• Plasma Cmax after administration of the unencapsulated eMS formulation

  Maximum plasma concentration Method of Determination: Observed directly from the data

  Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3)

• Plasma AUClast after administration of the unencapsulated eMS formulation

  Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration (Clast) Method of Determination: AUClast + (Clast/kel) Where Clast is the predicted plasma concentration at the last quantifiable time point and kel is the elimination rate constant estimated from the loglinear regression analysis.

  Day 1, Pre-dose, hour 1,2,4,6,8,12,24,48,72,96,144 (Periods 1-3)

Study Arms (2)

Three Period Treatment Sequence

EXPERIMENTAL

Participants will receive a single 250 mg crizotinib dose of the formulated capsule(FC) formulation, a single 250 mg crizotinib dose of the encapsulated microsphere (eMS) formulation administered by sprinkling the contents into a dry glass vial, and a single 250 mg crizotinib dose of the encapsulated microsphere (eMS) formulation (administered as intact capsules)

Drug: Crizotinib

Two Period Treatment Sequence

EXPERIMENTAL

Participants will receive a single 250 mg crizotinib dose of the formulated capsule(FC) formulation, a single 250 mg crizotinib dose of the encapsulated microsphere (eMS) formulation administered by sprinkling the contents into a dry glass vial

Drug: Crizotinib

Interventions

Crizotinib DRUG

A single 250 mg crizotinib dose of the FC formulation

Also known as: Treatment A

Three Period Treatment Sequence; Two Period Treatment Sequence

Eligibility Criteria

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

You may qualify if:

• Participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD).
• Male and female of non-childbearing potential participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in theICD and in this protocol.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
• Any condition possibly affecting crizotinib absorption (eg, gastrectomy, cholecystectomy, appendectomy).
• History of HIV infection, chronic hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody (HCVAb).
• Positive COVID-19 test.
• History of sensitivity to heparin or heparin induced thrombocytopenia.
• Known history of hypersensitivity to crizotinib or any components of the formulations.
• Other medical or psychiatric condition: recent or active suicidal ideation/behavior, laboratory abnormality or conditions related to the COVID-19 pandemic that make the participant inappropriate.
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of crizotinib.
• Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of crizotinib (whichever is longer).
• Positive urine drug test or cotinine test.
• Supine BP \>=140 mm Hg (systolic) or \>=90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP \>=140 mm Hg (systolic) or \>=90 mm Hg (diastolic), BP should be repeated 2 more times.
• Any clinically significant abnormality in 12-lead ECG, including QTcF \>450 msec, Computer-interpreted ECGs may be overread by a physician experienced in reading ECGs before excluding participants.
• AST or ALT level \> (ULN); TBili level \>ULN; participants with a history of Gilbert's syndrome may have direct bilirubin \<= ULN; eGFR \<90 ml/min/1.73 m2 per CKD-EPI equation.
• Male participants who are unwilling or unable to comply with the contraception requirement.
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

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

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 23, 2021
• Study Start: April 16, 2021
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: January 20, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)