Bioequivalence Study for Crizotinib Encapsulated Microsphere Formulation (eMS)

A PHASE 1, OPEN-LABEL, CROSSOVER STUDY TO ESTABLISH BIOEQUIVALENCE OF AN ENCAPSULATED MICROSPHERE FORMULATION (eMS) TO THE FORMULATED CAPSULE (FC) OF CRIZOTINIB IN HEALTHY ADULT PARTICIPANTS

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

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Crizotinib; Drug: Crizotinib; Drug: Crizotinib

Detailed Description

In order to overcome the poor taste/palatability associated with the original oral solution formulation of crizotinib for pediatric patients, an encapsulated microsphere (eMS) formulation with improved palatability compared with the oral solution and acceptable PK characteristics was developed.

The primary objective of this study is to establish the bioequivalence of the eMS formulation to the current commercial formulation, ie, formulated capsule (FC), in adult healthy participants to support the commercialization of this new formulation.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD).
2. 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.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
5. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in theICD and in this protocol.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
2. Any condition possibly affecting crizotinib absorption (eg, gastrectomy, cholecystectomy, appendectomy).
3. 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).
4. Positive COVID-19 test.
5. History of sensitivity to heparin or heparin induced thrombocytopenia.
6. Known history of hypersensitivity to crizotinib or any components of the formulations.
7. 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.
8. 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.
9. Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of crizotinib (whichever is longer).
10. Positive urine drug test or cotinine test.
11. 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.
12. 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.
13. 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.
14. Male participants who are unwilling or unable to comply with the contraception requirement.
15. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
16. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
17. Participants who currently smoke.
18. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
19. Investigator site staff members or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Three Period Treatment Sequence; 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; A single 250 mg crizotinib dose of the FC formulation; Other Names: Treatment A; Drug: Crizotinib; A single 250 mg crizotinib dose of the encapsulated microsphere (eMS) formulation administered by sprinkling the contents into a dry glass vial; Other Names: Treatment B; Drug: Crizotinib; A single 250 mg crizotinib dose of the single 250 mg crizotinib dose of the encapsulated microsphere (eMS) formulation (administered as intact capsules) . The intact capsules will be swallowed whole.; Other Names: Treatment C
Experimental: Two Period Treatment Sequence; 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; A single 250 mg crizotinib dose of the FC formulation; Other Names: Treatment A; Drug: Crizotinib; A single 250 mg crizotinib dose of the encapsulated microsphere (eMS) formulation administered by sprinkling the contents into a dry glass vial; Other Names: Treatment B; Drug: Crizotinib; A single 250 mg crizotinib dose of the single 250 mg crizotinib dose of the encapsulated microsphere (eMS) formulation (administered as intact capsules) . The intact capsules will be swallowed whole.; Other Names: Treatment C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Actual): December 15, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): January 20, 2022
• Last Update Submitted That Met QC Criteria: January 18, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Healthy adult participants; Crizotinib; Encapsulated Microsphere Formulation
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: A8081074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No