Healthy Participants
Conditions
Keywords
Bioavailability, Food Effect, Bosutinib, Maximum Observed Plasma Concentration (Cmax), Area Under the Curve (AUC)
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.
Interventions
Bosutinib four 25 mg capsule taken after a high-fat and high calorie breakfast
DRUGBosutinib
Bosutinib 100 mg capsule taken after an overnight fast of at least 10 hours
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
A Phase 1, open-label, randomized, single dose, 3-period, 4 sequence, crossover study in healthy participants
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) 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 | 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 |
| Maximum Observed Plasma Concentration (Cmax) 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 | Cmax was the maximum observed plasma concentration. The geometric coefficient of variation was reported as percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | CL/F was the apparent clearance after oral dose and was determined as dose/AUCinf. The geometric coefficient of variation was reported as percentage. |
| 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 | 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. |
| 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 | AUClast was the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration. |
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. |
| 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 | 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. |
| 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 | Tmax was the time to reach maximum observed plasma concentration and was observed directly from data as time of the first occurrence. |
Countries
Belgium
Participant flow
Pre-assignment details
A total of 32 participants were assigned to the study intervention, of whom 26 participants received all the randomized treatment by sequence and 25 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A -> Treatment B -> Treatment C Treatment A: 1 × 100 mg bosutinib capsule under fed condition. Treatment B: 4 × 25 mg bosutinib capsules under fed condition. Treatment C: 1 × 100 mg bosutinib capsule under fasted condition. The participant took Treatment A in Period 1, followed with at least 14-days washout between successive bosutinib doses, and then Treatment B in Period 2, followed with another at least 14-days washout between successive bosutinib doses, and then Treatment C in Period 3. | 8 |
| Treatment B -> Treatment A -> Treatment C Treatment A: 1 × 100 mg bosutinib capsule under fed condition. Treatment B: 4 × 25 mg bosutinib capsules under fed condition. Treatment C: 1 × 100 mg bosutinib capsule under fasted condition. The participant took Treatment B in Period 1, followed with at least 14-days washout between successive bosutinib doses, and then Treatment A in Period 2, followed with another at least 14-days washout between successive bosutinib doses, and then Treatment C in Period 3. | 10 |
| Treatment A ->Treatment B Treatment A: 1 × 100 mg bosutinib capsule under fed condition. Treatment B: 4 × 25 mg bosutinib capsules under fed condition.The participant took Treatment A in Period 1, followed with at least 14-days washout between successive bosutinib doses, and then Treatment B in Period 2. | 7 |
| Treatment B->Treatment A Treatment A: 1 × 100 mg bosutinib capsule under fed condition. Treatment B: 4 × 25 mg bosutinib capsules under fed condition. The participant took Treatment B in Period 1, followed with at least 14-days washout between successive bosutinib doses, and then Treatment A in Period 2. | 7 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 1 | 0 | 0 |
| Period 1 | No longer meets eligibility criteria | 0 | 1 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Period 2 | Adverse Event | 1 | 0 | 0 | 0 |
| Period 2 | No longer meets eligibility criteria | 0 | 1 | 0 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Period 3 | Adverse Event | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment A -> Treatment B -> Treatment C | Treatment B -> Treatment A -> Treatment C | Treatment A ->Treatment B | Treatment B->Treatment A | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.5 years | 38.0 years | 42.0 years | 42.0 years | 39.5 years |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 8 Participants | 10 Participants | 6 Participants | 6 Participants | 30 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 7 Participants | 7 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 31 | 0 / 12 |
| other Total, other adverse events | 13 / 30 | 20 / 31 | 5 / 12 |
| serious Total, serious adverse events | 0 / 30 | 0 / 31 | 0 / 12 |
Outcome results
Primary
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
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
Population: The pharmacokinetic (PK) parameter analysis population is defined as all subjects randomized and treated who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib | 591.3 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib | 591.7 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 39 |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib | 479.4 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
Comparison: For comparison of Bosutinib 4\*25 mg Capsule Fed vs. Bosutinib 1\*100 mg Capsule Fed, the model is a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.~The reference treatment of Bosutinib 4\*25 mg Capsule Fed is Bosutinib 1\*100 mg Capsule Fed.90% CI: [93.72, 104.93]Mixed Models Analysis
Comparison: For comparison of Bosutinib 1\*100 mg Capsule Fed vs. Bosutinib 1\*100 mg Capsule Fasted, the model is a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.~The reference treatment of Bosutinib 1\*100 mg Capsule Fed is Bosutinib 1\*100 mg Capsule Fasted.90% CI: [109.28, 169.01]Mixed Models Analysis
Primary
Maximum Observed Plasma Concentration (Cmax) for Bosutinib
Cmax was the maximum observed plasma concentration. The geometric coefficient of variation was reported as percentage.
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
Population: The PK parameter analysis population is defined as all subjects randomized and treated who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Maximum Observed Plasma Concentration (Cmax) for Bosutinib | 17.80 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Maximum Observed Plasma Concentration (Cmax) for Bosutinib | 16.68 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Maximum Observed Plasma Concentration (Cmax) for Bosutinib | 10.75 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
Comparison: For comparison of Bosutinib 4\*25 mg Capsule Fed vs. Bosutinib 1\*100 mg Capsule Fed, the model is a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.~The reference treatment of Bosutinib 4\*25 mg Capsule Fed is Bosutinib 1\*100 mg Capsule Fed.90% CI: [90.08, 97.61]Mixed Models Analysis
Comparison: For comparison of Bosutinib 1\*100 mg Capsule Fed vs. Bosutinib 1\*100 mg Capsule Fasted, the model is a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.~The reference treatment of Bosutinib 1\*100 mg Capsule Fed is Bosutinib 1\*100 mg Capsule Fasted90% CI: [130.25, 202.84]Mixed Models Analysis
Secondary
Apparent Clearance After Oral Dose (CL/F) of Bosutinib
CL/F was the apparent clearance after oral dose and was determined as dose/AUCinf. The geometric coefficient of variation was reported as percentage.
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
Population: The PK parameter analysis population is defined as all subjects randomized and treated who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Apparent Clearance After Oral Dose (CL/F) of Bosutinib | 169.3 liter/hour | Geometric Coefficient of Variation 32 |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Apparent Clearance After Oral Dose (CL/F) of Bosutinib | 169.0 liter/hour | Geometric Coefficient of Variation 39 |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Apparent Clearance After Oral Dose (CL/F) of Bosutinib | 208.5 liter/hour | Geometric Coefficient of Variation 30 |
Secondary
Apparent Volume of Distribution After Oral Dose (Vz/F) of Bosutinib
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.
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
Population: The PK parameter analysis population is defined as all subjects randomized and treated who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Apparent Volume of Distribution After Oral Dose (Vz/F) of Bosutinib | 11130 liter | Geometric Coefficient of Variation 25 |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Apparent Volume of Distribution After Oral Dose (Vz/F) of Bosutinib | 10650 liter | Geometric Coefficient of Variation 24 |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Apparent Volume of Distribution After Oral Dose (Vz/F) of Bosutinib | 12870 liter | Geometric Coefficient of Variation 19 |
Secondary
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib
AUClast was the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.
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
Population: The PK parameter analysis population is defined as all subjects randomized and treated who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib | 455.6 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40 |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib | 446.4 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 45 |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib | 301.6 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 52 |
Comparison: For comparison of Bosutinib 4\*25 mg Capsule Fed vs. Bosutinib 1\*100 mg Capsule Fed, the model is a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.~The reference treatment of Bosutinib 4\*25 mg Capsule Fed is Bosutinib 1\*100 mg Capsule Fed.90% CI: [93.83, 102.8]Mixed Models Analysis
Comparison: For comparison of Bosutinib 1\*100 mg Capsule Fed vs. Bosutinib 1\*100 mg Capsule Fasted, the model is a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.~The reference treatment of Bosutinib 1\*100 mg Capsule Fed is Bosutinib 1\*100 mg Capsule Fasted.90% CI: [117.88, 182.58]Mixed Models Analysis
Secondary
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
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.
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)
Population: All participants randomly assigned to study intervention and who take at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen (EU/dL) ≥1 | 1 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Bilirubin ≥1 | 0 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Specific Gravity (scalar) <1.003 | 0 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Coronavirus 19 Molecular (Scalar) >0 | 1 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes/Leukocytes (%) >1.2*upper normal limit (ULN) | 7 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 4 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Creatine Kinase (U/L) >2.0* ULN | 1 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (U/L) > 3.0*ULN | 1 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Specific Gravity (scalar) >1.030 | 1 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Coronavirus 19 Molecular (Scalar) >0 | 2 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes/Leukocytes (%) >1.2*upper normal limit (ULN) | 8 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (U/L) > 3.0*ULN | 0 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Creatine Kinase (U/L) >2.0* ULN | 0 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen (EU/dL) ≥1 | 1 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Specific Gravity (scalar) <1.003 | 2 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Specific Gravity (scalar) >1.030 | 0 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 4 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Bilirubin ≥1 | 1 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Creatine Kinase (U/L) >2.0* ULN | 0 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes/Leukocytes (%) >1.2*upper normal limit (ULN) | 3 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Specific Gravity (scalar) >1.030 | 0 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (U/L) > 3.0*ULN | 0 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Bilirubin ≥1 | 0 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Coronavirus 19 Molecular (Scalar) >0 | 1 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen (EU/dL) ≥1 | 0 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 0 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Specific Gravity (scalar) <1.003 | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
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)
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with severe AEs | 0 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued from study due to adverse events | 0 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with SAEs | 0 Participants |
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with TEAEs | 13 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued from study due to adverse events | 2 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with severe AEs | 0 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with SAEs | 0 Participants |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with TEAEs | 20 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants discontinued from study due to adverse events | 1 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with TEAEs | 5 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with SAEs | 0 Participants |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Particiapnts with severe AEs | 0 Participants |
Secondary
Terminal Elimination Half-Life (t1/2) of Bosutinib
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.
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
Population: The PK parameter analysis population is defined as all subjects randomized and treated who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Terminal Elimination Half-Life (t1/2) of Bosutinib | 47.22 hour | Standard Deviation 11.753 |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Terminal Elimination Half-Life (t1/2) of Bosutinib | 46.01 hour | Standard Deviation 13.434 |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Terminal Elimination Half-Life (t1/2) of Bosutinib | 43.28 hour | Standard Deviation 7.6939 |
Secondary
Time for Cmax (Tmax) of Bosutinib
Tmax was the time to reach maximum observed plasma concentration and was observed directly from data as time of the first occurrence.
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
Population: The PK parameter analysis population is defined as all subjects randomized and treated who have at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: Bosutinib 1*100 mg Capsule Fed | Time for Cmax (Tmax) of Bosutinib | 6.00 hour |
| Treatment B: Bosutinib 4*25 mg Capsule Fed | Time for Cmax (Tmax) of Bosutinib | 6.00 hour |
| Treatment C: Bosutinib 1*100 mg Capsule Fasted | Time for Cmax (Tmax) of Bosutinib | 6.00 hour |