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Completed

NCT Number: NCT05032690

Evaluation of the Relative Bioavailability of Bosutinib Capsules Under Fed Condition and Estimation of Food Effect on Orally Administered Bosutinib Capsule

This study is intended to estimate the bioavailability of a single 100 mg bosutinib capsules relative to four 25 mg capsules under fed condition in adult healthy participants and to estimate the effect of a high-fat, high-calorie meal on the bioavailability of a single 100 mg capsule of bosutinib relative to fasted condition in adults healthy participants. The comparisons will be performed using the pharmacokinetic parameters that define the rate and extend of absorption (Cmax, AUC). Statistical analyses will be performed after the administration of a single 100 mg dose under fed condition as the Reference treatment and the four 25 mg capsules as the Test treatment for the first comparison, and after administration of a single 100 mg dose under fasted condition as the Reference treatment and the 100 mg capsule under fed condition as the Test treatment for the second comparison.

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Key information

Conditions

Healthy Participants

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Female participants of non-childbearing potential and/or male participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD)
  • participants who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination, vital signs which include BP and pulse rate measurement, clinical laboratory tests, and electrocardiogram (ECG).
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures

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 (eg, gastrectomy, cholecystectomy).
  • History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg,hepatitis B surface antigen (HBcAb) or hepatitis C antibody (HCVAb).
  • 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:
  • estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) <90 mL/min/1.73 m2;
  • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >upper limit of normal (ULN);
  • 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;
  • Amylase and lipase level > ULN.

Treatment and study plan

Bosutinib capsule

Drug

Bosutinib four 25 mg capsule taken after a high-fat and high calorie breakfast

Bosutinib

Drug

Bosutinib 100 mg capsule taken after an overnight fast of at least 10 hours

Primary outcomes

  1. Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib

    Time frame: 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

  2. Maximum Observed Plasma Concentration (Cmax) for Bosutinib

    Time frame: 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.

Secondary outcomes

  1. Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib

    Time frame: 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.

  2. Time for Cmax (Tmax) of Bosutinib

    Time frame: 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.

  3. Apparent Clearance After Oral Dose (CL/F) of Bosutinib

    Time frame: 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.

  4. Apparent Volume of Distribution After Oral Dose (Vz/F) of Bosutinib

    Time frame: 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.

  5. Terminal Elimination Half-Life (t1/2) of Bosutinib

    Time frame: 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.

  6. Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

    Time frame: On Days 4, 5, 7 of Periods 1 and 2 for all participants, on Period 3 Days 4, 5, 7 for participants who were assigned to treatment sequences A=>B=>C and B=>A=>C, and at early termination/discontinuation (if applicable)

    Laboratory tests included hematology tests, chemistry tests, and urinalysis tests. Laboratory parameters with at least 1 occurrence meeting the pre-defined criteria are reported for this outcome measure.

  7. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Post first dose on Period 1 Day 1 up to 28 days post the last dose of study intervention (up to a maximum of 75 days)

    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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

A PHASE 1, RANDOMIZED, OPEN-LABEL, 3-PERIOD, 4-SEQUENCE, CROSSOVER, SINGLE-DOSE STUDY TO COMPARE THE BIOAVAILABILITY OF ORALLY ADMINISTERED BOSUTINIB CAPSULES AND TO ESTIMATE THE EFFECT OF FOOD ON BOSUTINIB CAPSULE

Important dates

Study start
2022
Primary completion
2022
Study completion
2022
First posted
Sep 2, 2021
Registry last updated
Sep 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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