Palatability (Taste) of Oral Formulations of Bosutinib
Palatability (Taste) of Oral Formulations of Bosutinib
Healthy Adult Volunteer Taste Study of Oral Formulations of Bosutinib for Pediatric Use. This
 will be a single-blind, randomized, multiple-period (dosing over 4 days) study in healthy
 male and/or female participants. Approximately 8 participants will assess the sensory
 attributes of different powder for oral suspension (POS) formulations.
Taste evaluations for the formulations (Formulations A to N) in Sessions 1 to 4 each contains
 4 periods. All the planned formulations in this study will have a bosutinib amount equal to
 200 mg in each taste assessment. Session 1 consists of bosutinib POS, sorbitol base in water
 (A); bosutinib POS, mannitol base in water (B); and bosutinib capsules to be opened into
 water (C). Session 2 consists of bosutinib POS, mannitol base in low % (D) and in high % (E)
 sodium saccharine sweetener vehicles, respectively; bosutinib POS, mannitol base in low % (F)
 and high % (G) strawberry flavour vehicles, respectively. Session 3 consists of bosutinib
 capsules to be opened into low % (H) and high % (I) sodium saccharine sweetener vehicles,
 respectively; bosutinib capsules to be opened into low % (J) and high % (K) strawberry
 flavour vehicles, respectively. Session 4 consists of bosutinib capsules opened onto apple
 sauce (L); bosutinib capsules opened onto full fat natural yoghurt (M); and bosutinib
 capsules to be opened into water (N). Participants will be assigned to one of the treatment
 sequences available for each session. Except at session 4 for treatments L and M, each
 formulation will be presented to the participants in a blinded fashion.

 Participants will be required to not swallow, rather to only swish the bosutinib containing
 liquid in their mouths for approximately 10 seconds, after which the liquid will be spat out.
 Each participant will record the sensory attributes at timed intervals of 0 (immediately
 after dosing), 5, 10 and 20 minutes after spitting using a Bosutinib Taste Assessment
 Questionnaire.
Inclusion Criteria:

 Age and Sex:

 1. Female participants of non-childbearing potential and/or male participants able to
 father children must be 18 to 55 years of age, inclusive, at the time of signing the
 informed consent document (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, limited physical examination,
 including blood pressure (BP) and pulse rate measurement, or clinical laboratory
 tests.

 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. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >45 kg (99 lbs).

 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 informed consent
 document (ICD) and in this protocol.

 Exclusion Criteria:

 Medical Conditions:

 1. Evidence or history of clinically significant hematological, renal, endocrine,
 pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or
 allergic disease (including drug allergies, but excluding untreated, asymptomatic,
 seasonal allergies at the time of dosing).

 2. A history of hypersensitivity to the active compounds or to any inactive ingredients
 (excipients) contained in the formulations.

 3. Participants with conditions that affect their ability to taste - ie, dysgeusia,
 respiratory infection, cold, etc.

 4. History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C;
 positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core
 antibody (HBcAb) or hepatitis C antibody (HCVAb). As an exception, a positive
 hepatitis B surface antibody (HBsAb) as a result of participant vaccination is
 permissible.

 5. Other acute or chronic medical or psychiatric condition including recent (within the
 past year) or active suicidal ideation or behavior or laboratory abnormality that may
 increase the risk associated with study participation or investigational product
 administration or may interfere with the interpretation of study results and, in the
 judgment of the investigator, would make the participant inappropriate for entry into
 this study.

 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
 investigational product. (Refer to Section 6.5 for additional details).

 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 investigational
 product used in this study (whichever is longer).

 Diagnostic Assessments:

 8. A positive urine drug test.

 9. Use of tobacco-containing products.

 10. Screening supine blood pressure (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.

 11. Baseline 12 lead electrocardiogram (ECG) that demonstrates clinically relevant
 abnormalities that may affect participant safety or interpretation of study results
 (eg, baseline corrected QT (QTc) interval >450 msec, complete left bundle branch block
 [LBBB], signs of an acute or indeterminate age myocardial infarction, ST T interval
 changes suggestive of myocardial ischemia, second or third degree atrioventricular
 [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 QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be
 repeated 2 more times and the average of the 3 QTc 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.

 12. 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:

 -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 1.5 ×
 upper limit of normal (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:

 13. History of alcohol abuse or binge drinking and/or any other illicit drug use or
 dependence within 6 months of Screening. Binge drinking is defined as a pattern of
 consuming 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a
 general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces
 (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).

 14. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
 within 60 days prior to dosing.

 15. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
 section of this protocol.

 16. Investigator site staff members directly involved in the conduct of the study and
 their family members, site staff members otherwise supervised by the investigator, or
 Pfizer employees, including their family members, directly involved in the conduct of
 the study.

 17. Male participants with partners currently pregnant; male participants able to father
 children who are unwilling or unable to use a highly effective method of contraception
 as outlined in this protocol for the duration of the study and for at least 28 days
 after the last dose of investigational product or longer based upon the compound's
 half-life characteristics.