Bioequivalence Study for Crizotinib Encapsulated Microsphere Formulation (eMS)

• ClinicalTrials.gov Identifier: NCT04856293
• Recruitment Status: Completed
• First Posted: April 23, 2021
• Last Update Posted: January 20, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: Crizotinib	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: April 16, 2021
• Actual Primary Completion Date: December 15, 2021
• Actual Study Completion Date: December 15, 2021

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Treatment B

Outcome Measures

Primary Outcome Measures :

1. Plasma AUCinf after administration of the FC formulation [ Time Frame: Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3) ]

   Area under the plasma concentration-time profile from time zero extrapolated to infinite time

   Method of Determination:

   Linear-log trapezoidal method

2. Plasma Cmax after administration of the FC formulation [ Time Frame: Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3) ]

   Maximum plasma concentration

   Method of Determination:

   Observed directly from the data

3. Plasma AUClast after administration of the FC formulation [ Time Frame: Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3) ]

   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.

4. Plasma AUCinf after administration of the unencapsulated eMS formulation [ Time Frame: Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3) ]

   Area under the plasma concentration-time profile from time zero extrapolated to infinite time

   Method of Determination:

   Linear-log trapezoidal method

5. Plasma Cmax after administration of the unencapsulated eMS formulation [ Time Frame: Day 1, Pre-dose, hour 1, 2,4,6,8,12,24,48,72,96,144 (Periods 1-3) ]

   Maximum plasma concentration

   Method of Determination:

   Observed directly from the data

6. Plasma AUClast after administration of the unencapsulated eMS formulation [ Time Frame: Day 1, Pre-dose, hour 1,2,4,6,8,12,24,48,72,96,144 (Periods 1-3) ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Connecticut

New Haven Clinical Research Unit

New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04856293
• Other Study ID Numbers: A8081074
• First Posted: April 23, 2021
• Last Update Posted: January 20, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

Crizotinib; Encapsulated Microsphere Formulation; Healthy adult participants

Additional relevant MeSH terms:

Crizotinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action