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

NCT05032690 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: B18710622021-004911-24
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Participants

Keywords

Bioavailability; Food Effect; Bosutinib; Maximum Observed Plasma Concentration (Cmax); Area Under the Curve (AUC)

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (7)

• 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

• Time for Cmax (Tmax) of 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

• Apparent Clearance After Oral Dose (CL/F) of 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

• Apparent Volume of Distribution After Oral Dose (Vz/F) of 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

• Terminal Elimination Half-Life (t1/2) of 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

Study Arms (4)

Treatment B: Bosutinib four 25 mg capsule after meal

EXPERIMENTAL

Bosutinib four 25 mg capsule taken after a high-fat and high-calorie breakfast for comparison 1

Drug: Bosutinib capsule

Treatment A: Bosutinib 100 mg capsule after meal (active comparator)

ACTIVE COMPARATOR

Bosutinib 100 mg capsule taken after a high-fat and high-calorie breakfast for comparison 1

Drug: Bosutinib capsule

Treatment A: Bosutinib 100 mg capsule after meal (experimental)

EXPERIMENTAL

Bosutinib 100 mg capsule taken after a high-fat and high-calorie breakfast for comparison 2

Drug: Bosutinib capsule

Treatment C: Bosutinib 100 mg capsule after fasting

ACTIVE COMPARATOR

Bosutinib 100 mg capsule taken after an overnight fast of at least 10 hours for comparison 2

Drug: Bosutinib

Interventions

Bosutinib capsule DRUG

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

Treatment B: Bosutinib four 25 mg capsule after meal

Bosutinib DRUG

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

Treatment C: Bosutinib 100 mg capsule after fasting

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Clinical Research Unit - Brussels

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

Location

Related Links

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

MeSH Terms

Interventions

bosutinib

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase 1, open-label, randomized, single dose, 3-period, 4 sequence, crossover study in healthy participants

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 2, 2021
• Study Start: January 19, 2022
• Primary Completion: June 25, 2022
• Study Completion: June 25, 2022
• Last Updated: September 20, 2024
• Results First Posted: September 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)