Bioavailability of Bosutinib Administered as Capsule Contents Mixed With Applesauce or Yogurt Relative to Intact Capsules Under Fed Condition

A PHASE 1, OPEN-LABEL, RANDOMIZED, 3-PERIOD, 6-SEQUENCE, CROSSOVER STUDY TO EVALUATE THE BIOAVAILABILITY OF BOSUTINIB ADMINISTERED AS CAPSULE CONTENTS MIXED WITH APPLESAUCE OR YOGURT RELATIVE TO INTACT CAPSULES IN HEALTHY PARTICIPANTS UNDER FED CONDITION

This study is intended to estimate the relative bioavailability of a single 500 mg dose of bosutinib when administered as capsule contents mixed with applesauce or yogurt to intact capsules under fed condition in adult healthy participants. The comparisons will be performed using the pharmacokinetic parameters that define the rate and extent of absorption, those are Cmax and AUC. Statistical analyses will be performed comparing these parameters calculated after administration of a single 500 mg dose with the intact capsule formulation (100 mg x 5) as the Reference treatment and the capsule contents mixed with applesauce or yogurt (100 mg x 5) as the Test treatments.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female participants of non childbearing potential and/or male participants must be 18 to 54 years of age, inclusive, at the time of signing the informed consent document (ICD).
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, dermatological, or allergic disease.
• Any condition possibly affecting drug absorption.

• Participants 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:

  1. estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) < 90 mL/min/1.73 m2;
  2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > upper limit of normal (ULN);
  3. Serum (total and direct) bilirubin level > ULN; participants 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 <= ULN;
  4. Amylase and lipase levels > ULN.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bosutinib capsule contents mixed with applesauce; Bosutinib capsule contents mixed with applesauce to healthy participants	Drug: Bosutinib capsule; 500 mg dose of bosutinib capsule contents mixed with applesauce; Drug: Bosutinib capsule; 500 mg dose of bosutinib capsule contents mixed with yogurt; Drug: Bosutinib capsule; 500 mg dose of intact bosutinib capsules
Experimental: Bosutinib capsule contents mixed with yogurt; Bosutinib capsule contents mixed with yogurt to healthy participants	Drug: Bosutinib capsule; 500 mg dose of bosutinib capsule contents mixed with applesauce; Drug: Bosutinib capsule; 500 mg dose of bosutinib capsule contents mixed with yogurt; Drug: Bosutinib capsule; 500 mg dose of intact bosutinib capsules
Active Comparator: Bosutinib intact capsules; Bosutinib intact capsules to healthy participants	Drug: Bosutinib capsule; 500 mg dose of bosutinib capsule contents mixed with applesauce; Drug: Bosutinib capsule; 500 mg dose of bosutinib capsule contents mixed with yogurt; Drug: Bosutinib capsule; 500 mg dose of intact bosutinib capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) for Bosutinib	Cmax was the maximum observed plasma concentration. The geometric coefficient of variation was reported as percentage.	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib	AUCinf was calculated as [AUClast+(Clast*/kel)], where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the Clast, Clast is the last quantifiable concentration, Clast* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The geometric coefficient of variation was reported as percentage.	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib	AUClast was the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration. Linear/Log trapezoidal method was used to determine AUClast. The geometric coefficient of variation was reported as percentage.	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Bosutinib	Tmax was the time to reach maximum observed plasma concentration and was observed directly from data as time of the first occurrence.	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
Apparent Clearance After Oral Dose (CL/F) for Bosutinib	CL/F was the apparent clearance after oral dose and was determined as dose/AUCinf. The geometric coefficient of variation was reported as percentage.	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
Apparent Volume of Distribution After Oral Dose (Vz/F) for Bosutinib	Vz/F was the apparent volume of distribution after oral dose. It was determined as dose/(AUCinf × kel), where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration time curve. The geometric coefficient of variation was reported as percentage.	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
Terminal Phase Half-life (t½ ) for Bosutinib	t½ was the terminal elimination plasma half-life. It was determined as Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
Number of Participants With Laboratory Abnormalities	Laboratory tests included hematology tests, chemistry tests, and urinalysis tests.	Post first dose and up to Day 7 in Period 3, or at early termination/discontinuation.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Severe Adverse Events (AEs), and Serious Adverse Events (SAEs)	TEAEs are those with initial onset or that worsen in severity after the first dose of the study medication. All AEs in the table below were TEAEs. An SAE is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event. Severe AEs were defined as AEs that interfered significantly with participant's usual function. Both SAEs and severe AEs were according to the investigator's assessment.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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): August 13, 2021
• Primary Completion (Actual): January 27, 2022
• Study Completion (Actual): January 27, 2022

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 1, 2021
• First Posted (Actual): June 8, 2021

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Bioavailability; bosutinib; Maximum Observed Plasma Concentration (Cmax); Area Under the Curve (AUC)
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Bosutinib
• Other Study ID Numbers: B1871063; 2021-000500-38 (EudraCT Number)

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