Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) MedDRA version: 22.0 Level: LLT Classification code 10082178 Term: Philadelphia positive chronic myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Bosutinib
Product Code: PF-05208763
Pharmaceutical Form: Capsule
INN or Proposed INN: bosutinib
Current Sponsor code: PF-05208763
Other descriptive name: BOSUTINIB MONOHYDRATE
Concentrat
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age and Sex: 1. 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 ICD. Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Type of Participant and Disease Characteristics: 2. Male and female 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 ECG. 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Weight: 4. BMI of 17.5 to 30.0 kg/m2; and a total body weight >50 kg (110 lb). Informed Consent: 5. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 66 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Medical Conditions: 1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, dermatological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). 3. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb or HCVAb. As an exception, a positive HBsAb as a result of participant vaccination is permissible. 4. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 5. A history of hypersensitivity to the active compounds or to any inactive ingredients (excipients) contained in the formulations. Prior/Concomitant Therapy: 6. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention (Refer to Section 6.5 for additional details). Hormone replacement therapy must be discontinued at least 28 days prior to the first dose of study medication. Prior/Concurrent Clinical Study Experience: 7. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Diagnostic Assessments: 8. A positive urine drug test. 9. Screening supine BP =140 mm Hg (systolic) or =90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is =140 mm Hg (systolic) or =90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant’s eligibility. 10. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTcF interval >450 msec, complete LBBB, signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant’s eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. 11. 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: AST or ALT level =1.5 × ULN; Total bilirubin level 1.5 × 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. Other Exclusions: 12. History of alcohol abuse or binge drinking and/or any other illicit drug use or depend
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To evaluate the PK of bosutinib when administered as a capsule and tablet formulation to healthy participants under fed condition. - To evaluate the safety and tolerability of bosutinib when administered as a capsule and tablet formulation to healthy participants under fed condition.;Primary end point(s): Plasma AUCinf and Cmax for bosutinib.;Timepoint(s) of evaluation of this end point: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, and 96 hours post the bosutinib dose.;Main Objective: To assess the bioequivalence of bosutinib pediatric capsule formulation (Test) to the commercial tablet formulation (Reference) at a 100 mg dose under fed condition in adult healthy participants. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): AUClast, Tmax, CL/F, Vz/F and t½ for bosutinib. Safety laboratory tests, vital signs, ECGs and AE monitoring.;Timepoint(s) of evaluation of this end point: Predose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, and 96 hours post the bosutinib dose. | — |
Countries
Netherlands
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed