Clinical trial NCT04916769: Bioavailability of Bosutinib Administered as Capsule Contents Mixed With Applesauce or Yogurt Relative to Intact Capsules Under Fed Condition
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Bioavailability
bosutinib
Maximum Observed Plasma Concentration (Cmax)
Area Under the Curve (AUC)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-06-08
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A Phase 1, open-label, randomized, single dose, 3-period, 6-sequence, crossover study in healthy participants
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib
timeFrame: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
measure: Maximum Observed Plasma Concentration (Cmax) for Bosutinib
timeFrame: 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:
measure: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib
timeFrame: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Bosutinib
timeFrame: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
measure: Apparent Clearance After Oral Dose (CL/F) for Bosutinib
timeFrame: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
measure: Apparent Volume of Distribution After Oral Dose (Vz/F) for Bosutinib
timeFrame: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
measure: Terminal Phase Half-life (t½ ) for Bosutinib
timeFrame: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Post first dose and up to Day 7 in Period 3, or at early termination/discontinuation.
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Severe Adverse Events (AEs), and Serious Adverse Events (SAEs)
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: