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

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Drug: Bosutinib capsule

• Registration Number: NCT04916769
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-06-01
• Study First Submitted QC: 2021-06-01
• Study First Posted: 2021-06-08
• Study Start: 2021-08-13
• Primary Completion: 2022-01-27
• Study Completion: 2022-01-27
• Results First Submitted: 2023-01-20
• Status Verified: 2024-11
• Results First Submitted QC: 2024-11-06
• Last Update Submitted: 2024-11-06
• Results First Posted: 2024-11-07
• Last Update Posted: 2024-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Bosutinib capsule contents mixed with applesauce	Bosutinib capsule	Bosutinib capsule contents mixed with applesauce to healthy participants
Bosutinib capsule contents mixed with yogurt	Bosutinib capsule	Bosutinib capsule contents mixed with yogurt to healthy participants
Bosutinib intact capsules	Bosutinib capsule	Bosutinib intact capsules to healthy participants

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) for Bosutinib	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose	Cmax was the maximum observed plasma concentration. The geometric coefficient of variation was reported as percentage.
Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose	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.

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose	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.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Bosutinib	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose	Tmax was the time to reach maximum observed plasma concentration and was observed directly from data as time of the first occurrence.
Apparent Clearance After Oral Dose (CL/F) for Bosutinib	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose	CL/F was the apparent clearance after oral dose and was determined as dose/AUCinf. The geometric coefficient of variation was reported as percentage.
Apparent Volume of Distribution After Oral Dose (Vz/F) for Bosutinib	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose	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.
Terminal Phase Half-life (t½ ) for Bosutinib	Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose	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.
Number of Participants With Laboratory Abnormalities	Post first dose and up to Day 7 in Period 3, or at early termination/discontinuation.	Laboratory tests included hematology tests, chemistry tests, and urinalysis tests.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Severe Adverse Events (AEs), and Serious Adverse Events (SAEs)	Up to 12 weeks	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.

Trial Locations

Locations (1)

Pfizer Clinical Research Unit - Brussels; 🇧🇪 Brussels, Bruxelles-capitale, Région DE, Belgium