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Study Evaluating SKI-606 (Bosutinib) In Advanced Malignant Solid Tumors

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00195260
Collaborator
(none)
151
Enrollment
19
Locations
4
Arms
37
Duration (Months)
7.9
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the safety and tolerability of oral SKI-606 (bosutinib) administered on a daily schedule to subjects with advanced malignant solid tumors and to define a maximum tolerated dose (MTD) in this subject population.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
151 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Dose-Escalation Study Of Oral SKI-606 In Subjects With Advanced Malignant Solid Tumors
Study Start Date :
Oct 1, 2004
Actual Primary Completion Date :
Nov 1, 2007
Actual Study Completion Date :
Nov 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose escalation

Dose finding study of monotherapy bosutinib in patients with advanced solid tumors.

Drug: bosutinib
Dose levels evaluated 50mg, 100mg, 200mg, 300mg, 400mg, 500mg and 600mg. 500mg was identified as MTD, however due to GI toxicities at that dose, 400mg was selected as the RP2D. Drug was administered as long as tolerable and disease under study did not worsen.
Experimental: Colorectal Cancer

Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.

Drug: bosutinib
400mg QD bosutinib, as long as tolerated and disease under study does not worsen.
Experimental: Pancreatic Cancer

Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.

Drug: bosutinib
400mg QD bosutinib, as long as tolerated and disease under study does not worsen.
Experimental: Non-Small Cell Lung Cancer (NSCLC)

Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.

Drug: bosutinib
400mg QD bosutinib, as long as tolerated and disease under study does not worsen.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 [Part 1 Baseline up to Day 28]

    DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of greater than or equal to (>=) 7-day duration or with fever >= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia >= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade >= 2 toxicity that requires >=14 days to resolve (to less than or equal to [=<] grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.

  2. Number of Participants With Adverse Events (AEs) by Seriousness [Baseline up to 30 days after last dose]

    Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category.

  3. Duration of Most Frequently Observed Adverse Events (AEs) [Baseline up to 30 days after last dose]

    The most frequently observed treatment-emergent AEs were gastrointestinal disorders which included diarrhea, nausea and vomiting. Duration of AE per event is calculated as AE stop date minus AE start date plus 1.

  4. Number of Participants With Best Overall Response (BOR) in Part 1 [Part 1 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose]

    BOR:investigator assessment by modified Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response:disappearance of all lesions. Partial Response (PR):>=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of >=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.

  5. Number of Participants With Best Overall Response (BOR) in Part 2 [Part 2 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose]

    BOR: investigator assessment by modified RECIST, recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. PR: >=30% decrease in SLDs of TLs taking as reference baseline SLD. PD: >=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of >=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.

  6. Maximum Tolerated Dose (MTD) in Part 1 [Part 1 Day 1 up to Day 28]

    MTD: highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1). DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of >= 7-day duration or with fever >= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia >= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade >= 2 toxicity that requires >=14 days to resolve (to =< grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.

Secondary Outcome Measures

  1. Maximum Tolerated Dose (MTD) for Prolonged Use [Part 1 Day 1 up to Day 28]

    MTD for prolonged use was the highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1) and was selected as recommended dose in Phase 2, due to substantial number of Grade 2 gastrointestinal toxicities observed in the MTD lead-in cohort (500 mg).

  2. Number of Participants With Change From Baseline in Laboratory Test Results [Baseline up to end of treatment (Week 95)]

    Criteria for potentially clinically significant (PCS) laboratory values: albumin <20, hemoglobin <80 gram/liter(g/L); alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase >5*upper limit of normal(ULN) milliunit/milliliter(mU/mL); bilirubin total, creatinine>3*ULN micromole/L; calcium <1.75 and >3.1,potassium <3 and >6, sodium <130, glucose <2.2,phosphorous <0.6 millimole/L; international normalized ratio >2*ULN, partial thromboplastin time, prothrombin time >2*ULN seconds; platelet count <50*10^9/L. Participants meeting at least 1 PCS criteria are reported.

  3. Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray [Baseline up to end of treatment (Week 95)]

    Number of participants with PCS ECG findings is reported on-therapy (OT) and at final visit (FV). Criteria for PCS ECG findings: heart rate (HR) =<45 beats/minute (bpm) and decrease (Dec) >15/>=120 bpm and decrease of >15 bpm; PR interval (Int) >=220 millisecond (msec), increase (Inc) >=20 msec, QRS Int >=120 msec, corrected QT (QTc) and QTc using fridericia formula(QTcF) Int >500 msec, increase >60 msec; no sinus rhythm; overall ECG abnormal. Participants with at least 1 measurement exceeding the criteria for PCS are reported.

  4. Concomitant Medications Used for Management of Adverse Events (AEs) [Day 1 up to end of treatment (Week 95)]

    Number of participants taking any non-study medications which were administered from Day 1 up to end of treatment (Week 95) as a management of an AE was to be reported.

  5. Change From Baseline in Karnofsky Performance Score [Baseline up to end of treatment (Week 95)]

    Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (complete healthy status). Higher score means higher ability to perform daily tasks.

  6. Number of Participants With Change From Baseline in Physical Examination [Baseline up to end of treatment (Week 95)]

    Physical examinations included body weight, height and vital signs and only finding that exceeded the criterion for PCS was weight. Criteria for weight was: an increase or decrease of >=10% from baseline.

  7. Number of Participants With Change From Baseline in Opthalmologic Examination [Baseline up to end of treatment (Week 95)]

    Ophthalmologic evaluation included visual acuity, funduscopic examination, and any clinically-significant abnormality.

  8. Overall Survival (OS) in Part 2 [Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation]

    Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from death case report forms (CRFs) or from follow-up contact data (where the participant current status was death).

  9. Progression Free Survival (PFS) in Part 2 [Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation]

    Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD, or from death CRFs).

  10. Maximum Observed Plasma Concentration (Cmax) [0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14]

  11. Time to Reach Maximum Observed Plasma Concentration (Tmax) [0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14]

  12. Plasma Decay Half-Life (t1/2) [0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  13. Area Under the Concentration-Time Curve (AUC) [0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14]

    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Steady state concentration was achieved at Day 15.

Other Outcome Measures

  1. Gene Expression at Baseline [Baseline]

    Gene expression profile was evaluated by measuring transcript levels of messenger RNA (mRNA) in peripheral blood samples. Expression profiling of mRNA: done to measure the expressed genome of mRNA transcripts or done in a gene-specific targeted manner.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Advanced or recurrent solid malignancy confirmed histologically or cytologically for which no effective therapy is available.

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.

  • Measurable disease as outlined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

  • Other inclusion applies.

Exclusion Criteria:

  • Use of any systemic antitumor agents or any investigational agent within 28 days before the first dose of test article is administered.

  • Prior exposure to SKI-606 or any other Src-kinase inhibitor, major surgery or radiotherapy within 14 days before the first dose of test article (recovery from previous surgery should be complete before day 1).

  • Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth (Treated CNS metastases must be stable for >= 2 weeks before day 1).

  • Other exclusion applies.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Pfizer Investigational Site Birmington Alabama United States 35233
2 Pfizer Investigational Site Scottsdale Arizona United States 85258
3 Pfizer Investigational Site Los Angeles California United States 90033
4 Pfizer Investigational Site Tampa Florida United States 33612
5 Pfizer Investigational Site Atlanta Georgia United States 30341
6 Pfizer Investigational Site Indianpolis Indiana United States 46202
7 Pfizer Investigational Site Baltimore Maryland United States 21287
8 Pfizer Investigational Site Detroit Michigan United States 48202
9 Pfizer Investigational Site Lansing Michigan United States 48910
10 Pfizer Investigational Site New York New York United States 10016
11 Pfizer Investigational Site New York New York United States 10032
12 Pfizer Investigational Site Charlotte North Carolina United States 28203
13 Pfizer Investigational Site Charlotte North Carolina United States 28211
14 Pfizer Investigational Site UNC Chapel Hill North Carolina United States 27514
15 Pfizer Investigational Site UNC Chapel Hill North Carolina United States 27759
16 Pfizer Investigational Site Cleveland Ohio United States 44106-1736
17 Pfizer Investigational Site San Antonio Texas United States 78258
18 Pfizer Investigational Site Tyler Texas United States 75702
19 Pfizer Investigational Site Seattle Washington United States 98104

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00195260
Other Study ID Numbers:
  • 3160A1-100
  • B1871012
First Posted:
Sep 19, 2005
Last Update Posted:
Feb 11, 2013
Last Verified:
Jan 1, 2013
Keywords provided by Pfizer
Solid tumors

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg Maximum Tolerated Dose (MTD) lead-in Colorectal Cancer Pancreatic Cancer Non-small Cell Lung Cancer (NSCLC)
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with pancreatic cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with NSCLC received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Period Title: Part 1: Dose Escalation
STARTED 4 4 6 7 7 7 10 6 0 0 0
COMPLETED 0 0 0 0 0 0 0 0 0 0 0
NOT COMPLETED 4 4 6 7 7 7 10 6 0 0 0
Period Title: Part 1: Dose Escalation
STARTED 0 0 0 0 0 0 0 0 37 38 25
COMPLETED 0 0 0 0 0 0 0 0 4 0 2
NOT COMPLETED 0 0 0 0 0 0 0 0 33 38 23

Baseline Characteristics

Arm/Group Title Part 1 RP2D 400 mg Total
Arm/Group Description Participants received bosutinib capsule orally once daily continuously in 21-day cycles in dose escalation schemes of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, MTD-lead in (500 mg) until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Total of all reporting groups
Overall Participants 51 100 151
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
57.00
(12.67)
60.30
(11.48)
59.10
(11.95)
Sex: Female, Male (Count of Participants)
Female
29
(participants) 56.9%
54
54%
83
55%
Male
22
43.1%
46
46%
68
45%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Dose-limiting Toxicities (DLT) in Part 1
Description DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of greater than or equal to (>=) 7-day duration or with fever >= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia >= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade >= 2 toxicity that requires >=14 days to resolve (to less than or equal to [=<] grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.
Time Frame Part 1 Baseline up to Day 28

Outcome Measure Data

Analysis Population Description
Safety population included all participants enrolled in a dose escalation cohort who had taken at least 1 dose of study medication.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 7 7 10 6
Number [participants]
0
0%
0
0%
1
0.7%
1
NaN
0
NaN
1
NaN
3
NaN
0
NaN
2. Primary Outcome
Title Number of Participants With Adverse Events (AEs) by Seriousness
Description Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category.
Time Frame Baseline up to 30 days after last dose

Outcome Measure Data

Analysis Population Description
Safety population included all participants who had taken at least 1 dose of study medication.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 7 7 10 6 100
AEs
4
7.8%
4
4%
6
4%
7
NaN
7
NaN
7
NaN
10
NaN
6
NaN
100
NaN
Serious adverse events (SAEs)
4
7.8%
3
3%
2
1.3%
3
NaN
5
NaN
2
NaN
7
NaN
3
NaN
47
NaN
3. Primary Outcome
Title Duration of Most Frequently Observed Adverse Events (AEs)
Description The most frequently observed treatment-emergent AEs were gastrointestinal disorders which included diarrhea, nausea and vomiting. Duration of AE per event is calculated as AE stop date minus AE start date plus 1.
Time Frame Baseline up to 30 days after last dose

Outcome Measure Data

Analysis Population Description
Safety population included all participants who had taken at least 1 dose of study medication.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD lead-in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 7 7 10 6 100
Diarrhea
1.0
NA
12.0
2.0
3.5
7.0
1.0
1.0
3.0
Nausea
2.0
1.0
1.0
9.0
4.0
7.0
3.0
7.0
13.0
Vomiting
2.5
1.0
NA
1.0
3.0
1.0
2.0
2.5
2.0
4. Primary Outcome
Title Number of Participants With Best Overall Response (BOR) in Part 1
Description BOR:investigator assessment by modified Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response:disappearance of all lesions. Partial Response (PR):>=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of >=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.
Time Frame Part 1 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose

Outcome Measure Data

Analysis Population Description
Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 3 3 6 6 6 6 4 3
Complete response
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
Partial response
0
0%
0
0%
0
0%
0
NaN
0
NaN
1
NaN
0
NaN
0
NaN
Stable disease
0
0%
2
2%
2
1.3%
5
NaN
3
NaN
2
NaN
4
NaN
2
NaN
Progressive disease
3
5.9%
1
1%
4
2.6%
1
NaN
2
NaN
3
NaN
0
NaN
1
NaN
Indeterminate
0
0%
0
0%
0
0%
0
NaN
1
NaN
0
NaN
0
NaN
0
NaN
Not done
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
5. Primary Outcome
Title Number of Participants With Best Overall Response (BOR) in Part 2
Description BOR: investigator assessment by modified RECIST, recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. PR: >=30% decrease in SLDs of TLs taking as reference baseline SLD. PD: >=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of >=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.
Time Frame Part 2 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose

Outcome Measure Data

Analysis Population Description
Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
Arm/Group Title Colorectal Cancer Pancreatic Cancer Non-small Cell Lung Cancer (NSCLC)
Arm/Group Description Participants with colorectal cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with pancreatic cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with NSCLC received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 34 22 19
Complete response
0
0%
0
0%
0
0%
Partial response
0
0%
0
0%
0
0%
Stable disease
10
19.6%
3
3%
9
6%
Progressive disease
24
47.1%
18
18%
9
6%
Indeterminate
0
0%
0
0%
0
0%
Not done
0
0%
1
1%
1
0.7%
6. Primary Outcome
Title Maximum Tolerated Dose (MTD) in Part 1
Description MTD: highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1). DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of >= 7-day duration or with fever >= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia >= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade >= 2 toxicity that requires >=14 days to resolve (to =< grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.
Time Frame Part 1 Day 1 up to Day 28

Outcome Measure Data

Analysis Population Description
Safety population included all participants enrolled in a dose escalation cohort who had taken at least 1 dose of study medication.
Arm/Group Title All Participant
Arm/Group Description All participants who received bosutinib capsule (50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, MTD-lead in) orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 51
Number [mg]
500
7. Secondary Outcome
Title Maximum Tolerated Dose (MTD) for Prolonged Use
Description MTD for prolonged use was the highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1) and was selected as recommended dose in Phase 2, due to substantial number of Grade 2 gastrointestinal toxicities observed in the MTD lead-in cohort (500 mg).
Time Frame Part 1 Day 1 up to Day 28

Outcome Measure Data

Analysis Population Description
Safety population included all participants enrolled in a dose escalation cohort who had taken at least 1 dose of study medication.
Arm/Group Title All Participant
Arm/Group Description All participants who received bosutinib capsule (50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, MTD-lead in) orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 51
Number [mg]
400
8. Secondary Outcome
Title Number of Participants With Change From Baseline in Laboratory Test Results
Description Criteria for potentially clinically significant (PCS) laboratory values: albumin <20, hemoglobin <80 gram/liter(g/L); alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase >5*upper limit of normal(ULN) milliunit/milliliter(mU/mL); bilirubin total, creatinine>3*ULN micromole/L; calcium <1.75 and >3.1,potassium <3 and >6, sodium <130, glucose <2.2,phosphorous <0.6 millimole/L; international normalized ratio >2*ULN, partial thromboplastin time, prothrombin time >2*ULN seconds; platelet count <50*10^9/L. Participants meeting at least 1 PCS criteria are reported.
Time Frame Baseline up to end of treatment (Week 95)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable (at least 1 on-therapy laboratory assessment) for this measure for each group respectively.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 7 7 8 6 96
Albumin (<20 g/L)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
Alkaline phosphatase (>5*ULN)
0
0%
1
1%
0
0%
0
NaN
0
NaN
1
NaN
0
NaN
0
NaN
5
NaN
Bilirubin total (>3*ULN)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
1
NaN
0
NaN
2
NaN
Calcium (<1.75 mmol/L)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
Calcium (>3.1 mmol/L)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
Creatinine (>3*ULN)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
2
NaN
Glucose (<2.2 mmol/L)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
2
NaN
Phosphorus (<0.6 mmol/L)
0
0%
0
0%
0
0%
1
NaN
1
NaN
0
NaN
0
NaN
0
NaN
0
NaN
Potassium (<3 mmol/L)
0
0%
1
1%
0
0%
0
NaN
0
NaN
0
NaN
1
NaN
0
NaN
1
NaN
Potassium (>6 mmol/L)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
Aspartate aminotransferase (> 5*ULN))
0
0%
0
0%
0
0%
0
NaN
0
NaN
1
NaN
0
NaN
0
NaN
5
NaN
Alanine aminotransferase (> 5*ULN)
0
0%
0
0%
0
0%
0
NaN
0
NaN
1
NaN
0
NaN
0
NaN
5
NaN
Sodium (<130 mmol/L)
0
0%
0
0%
0
0%
1
NaN
0
NaN
1
NaN
0
NaN
0
NaN
7
NaN
International normalized ratio (>2*ULN)
0
0%
1
1%
0
0%
1
NaN
2
NaN
0
NaN
0
NaN
1
NaN
6
NaN
Prothrombin time (>2*ULN)
0
0%
1
1%
0
0%
0
NaN
2
NaN
0
NaN
0
NaN
0
NaN
7
NaN
Partial thromboplastin time (>2*ULN)
0
0%
0
0%
0
0%
2
NaN
0
NaN
0
NaN
1
NaN
1
NaN
1
NaN
Hemoglobin (<80 g/L)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
3
NaN
Platelets (<50*10^9/L)
0
0%
1
1%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
0
NaN
9. Secondary Outcome
Title Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray
Description Number of participants with PCS ECG findings is reported on-therapy (OT) and at final visit (FV). Criteria for PCS ECG findings: heart rate (HR) =<45 beats/minute (bpm) and decrease (Dec) >15/>=120 bpm and decrease of >15 bpm; PR interval (Int) >=220 millisecond (msec), increase (Inc) >=20 msec, QRS Int >=120 msec, corrected QT (QTc) and QTc using fridericia formula(QTcF) Int >500 msec, increase >60 msec; no sinus rhythm; overall ECG abnormal. Participants with at least 1 measurement exceeding the criteria for PCS are reported.
Time Frame Baseline up to end of treatment (Week 95)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable (at least 1 on-therapy assessment) for this measure and 'n' represents participants evaluable under each category for each group respectively.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 7 7 10 6 93
OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93)
1
2%
0
0%
1
0.7%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
3
NaN
OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
2
NaN
3
NaN
OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93)
0
0%
0
0%
1
0.7%
1
NaN
1
NaN
0
NaN
1
NaN
0
NaN
8
NaN
OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93)
0
0%
0
0%
1
0.7%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
3
NaN
OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93)
0
0%
0
0%
1
0.7%
0
NaN
0
NaN
1
NaN
0
NaN
0
NaN
3
NaN
OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
3
NaN
OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
29
NaN
OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93)
3
5.9%
4
4%
5
3.3%
7
NaN
6
NaN
6
NaN
8
NaN
6
NaN
63
NaN
FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42)
0
0%
0
0%
1
0.7%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
1
NaN
0
NaN
4
NaN
FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
1
NaN
FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42)
0
0%
0
0%
0
0%
0
NaN
0
NaN
0
NaN
0
NaN
0
NaN
2
NaN
FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42)
1
2%
1
1%
1
0.7%
0
NaN
2
NaN
3
NaN
3
NaN
1
NaN
18
NaN
Chest X-ray (n=0,0,0,0,0,0,0,0,0)
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
NA
NaN
10. Secondary Outcome
Title Concomitant Medications Used for Management of Adverse Events (AEs)
Description Number of participants taking any non-study medications which were administered from Day 1 up to end of treatment (Week 95) as a management of an AE was to be reported.
Time Frame Day 1 up to end of treatment (Week 95)

Outcome Measure Data

Analysis Population Description
Data for this pre-specified outcome measure was not statistically summarized for analysis, but collected and reported in individual participant listings as planned.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 0 0 0 0 0 0 0 0 0
11. Secondary Outcome
Title Change From Baseline in Karnofsky Performance Score
Description Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (complete healthy status). Higher score means higher ability to perform daily tasks.
Time Frame Baseline up to end of treatment (Week 95)

Outcome Measure Data

Analysis Population Description
Data for this pre-specified outcome was collected but not statistically summarized for analysis as there were no clinically significant changes observed.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 0 0 0 0 0 0 0 0 0
12. Secondary Outcome
Title Number of Participants With Change From Baseline in Physical Examination
Description Physical examinations included body weight, height and vital signs and only finding that exceeded the criterion for PCS was weight. Criteria for weight was: an increase or decrease of >=10% from baseline.
Time Frame Baseline up to end of treatment (Week 95)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable (at least 1 on-therapy assessment) for this measure for each group respectively.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 7 7 7 6 87
Weight (decrease >=10%)
0
0%
0
0%
2
1.3%
2
NaN
0
NaN
0
NaN
0
NaN
0
NaN
3
NaN
Weight (increase >=10%)
1
2%
1
1%
0
0%
1
NaN
0
NaN
1
NaN
1
NaN
0
NaN
3
NaN
13. Secondary Outcome
Title Number of Participants With Change From Baseline in Opthalmologic Examination
Description Ophthalmologic evaluation included visual acuity, funduscopic examination, and any clinically-significant abnormality.
Time Frame Baseline up to end of treatment (Week 95)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who had taken at least 1 dose of study medication.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 7 7 10 6 100
Number [participants]
0
0%
0
0%
0
0%
1
NaN
0
NaN
0
NaN
0
NaN
0
NaN
4
NaN
14. Secondary Outcome
Title Overall Survival (OS) in Part 2
Description Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from death case report forms (CRFs) or from follow-up contact data (where the participant current status was death).
Time Frame Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation

Outcome Measure Data

Analysis Population Description
Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
Arm/Group Title Colorectal Cancer Pancreatic Cancer Non-small Cell Lung Cancer (NSCLC)
Arm/Group Description Participants with colorectal cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with pancreatic cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with NSCLC received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 34 22 19
Median (95% Confidence Interval) [weeks]
27.7
14.7
34.0
15. Secondary Outcome
Title Progression Free Survival (PFS) in Part 2
Description Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD, or from death CRFs).
Time Frame Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation

Outcome Measure Data

Analysis Population Description
Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
Arm/Group Title Colorectal Cancer Pancreatic Cancer Non-small Cell Lung Cancer (NSCLC)
Arm/Group Description Participants with colorectal cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with pancreatic cancer received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with NSCLC received bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 34 22 19
Median (95% Confidence Interval) [weeks]
6.0
6.0
5.7
16. Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Description
Time Frame 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description
Analysis population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg (Part 1 + Part 2) Bosutinib 500 mg Bosutinib 600 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal in both Part 1 and Part 2 participants. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 69 13 10
Day 1 (n = 4, 4, 6, 7, 54, 13, 10)
4.89
(3.69)
17.0
(9.75)
43.1
(26.9)
63.7
(34.7)
117.0
(69.0)
125.0
(63.2)
206.0
(190.0)
Day 15 (n = 3, 4, 5, 5, 69, 10, 2)
6.92
(3.07)
19.6
(3.31)
95.4
(60.0)
76.6
(37.0)
190.0
(116.0)
273.0
(197.0)
304.0
(NA)
17. Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description
Time Frame 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description
Analysis population included all participants who had taken at least one dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg (Part 1 + Part 2) Bosutinib 500 mg Bosutinib 600 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal in both Part 1 and Part 2 participants. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 69 13 10
Day 1 (n = 4, 4, 6, 7, 54, 13, 10)
6.01
4.08
6.00
6.00
4.00
4.00
6.00
Day 15 (n = 3, 4, 5, 5, 69, 10, 2)
4.00
3.50
4.00
4.02
4.00
5.00
3.53
18. Secondary Outcome
Title Plasma Decay Half-Life (t1/2)
Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description
Analysis population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg (Part 1 + Part 2) Bosutinib 500 mg Bosutinib 600 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal in both Part 1 and Part 2 participants. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 69 13 10
Day 1 (n = 3, 4, 6, 7, 47, 13, 10)
12.86
(7.36)
18.61
(4.91)
20.80
(6.07)
17.12
(6.01)
18.63
(7.67)
21.87
(7.39)
19.94
(5.47)
Day 15 (n = 3, 4, 5, 4, 53, 9, 2)
25.84
(12.26)
64.65
(67.31)
30.04
(20.13)
19.35
(7.54)
19.89
(16.72)
23.25
(15.00)
16.29
(NA)
19. Secondary Outcome
Title Area Under the Concentration-Time Curve (AUC)
Description AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Steady state concentration was achieved at Day 15.
Time Frame 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description
Analysis population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg (Part 1 + Part 2) Bosutinib 500 mg Bosutinib 600 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal in both Part 1 and Part 2 participants. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 4 4 6 7 69 13 10
Day 1 (n = 3, 4, 6, 7, 47, 13, 10)
129.0
(131.0)
284.0
(72.8)
920.0
(338.0)
1200.0
(736.0)
2340.0
(1230.0)
2950.0
(1470.0)
4300.0
(3310.0)
Day 15 (n = 3, 4, 5, 4, 58, 9, 2)
114.0
(33.3)
329.0
(58.1)
1670.0
(1130.0)
1170.0
(699.0)
2900.0
(1700.0)
3580.0
(1820.0)
4220.0
(NA)
20. Other Pre-specified Outcome
Title Gene Expression at Baseline
Description Gene expression profile was evaluated by measuring transcript levels of messenger RNA (mRNA) in peripheral blood samples. Expression profiling of mRNA: done to measure the expressed genome of mRNA transcripts or done in a gene-specific targeted manner.
Time Frame Baseline

Outcome Measure Data

Analysis Population Description
Data was not analyzed as the analysis was cancelled due to lack of samples provided from sites.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD-lead in
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants 0 0 0 0 0 0 0 0

Adverse Events

Time Frame
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD lead-in RP2D 400 mg
Arm/Group Description Bosutinib 50 milligram (mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 100 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 200 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 300 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 400 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 600 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Bosutinib 500 mg capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal.
All Cause Mortality
Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD lead-in RP2D 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD lead-in RP2D 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/4 (100%) 3/4 (75%) 2/6 (33.3%) 3/7 (42.9%) 5/7 (71.4%) 2/7 (28.6%) 7/10 (70%) 3/6 (50%) 47/100 (47%)
Blood and lymphatic system disorders
Anaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Coagulopathy 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Leukocytosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Cardiac disorders
Sinus tachycardia 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Atrial fibrillation 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Cardiac arrest 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Cardio-respiratory arrest 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Pericardial effusion 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Gastrointestinal disorders
Abdominal pain upper 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Small intestinal obstruction 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Vomiting 1/4 (25%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 1/100 (1%)
Diarrhoea 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 2/10 (20%) 0/6 (0%) 1/100 (1%)
Abdominal pain 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 0/100 (0%)
Nausea 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 2/100 (2%)
Duodenal ulcer 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Faecaloma 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Gastrointestinal haemorrhage 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Haematemesis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Intestinal ischaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Large intestinal obstruction 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Dysphagia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Ileus 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Peptic ulcer haemorrhage 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Ascites 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Upper gastrointestinal haemorrhage 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Abdominal discomfort 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Oesophageal stenosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Pancreatitis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Varices oesophageal 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
General disorders
Pyrexia 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Chest pain 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Chills 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Death 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Hepatobiliary disorders
Bile duct obstruction 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Hyperbilirubinaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Cholangitis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Hepatic failure 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Infections and infestations
Pneumonia 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Bacteraemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Pneumonia staphylococcal 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Sepsis 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Systemic candida 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Urinary tract infection 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Urinary tract infection staphylococcal 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Infection 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Abdominal abscess 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Bronchitis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Clostridium difficile colitis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Klebsiella bacteraemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Parotitis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Pneumonia klebsiella 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Injury, poisoning and procedural complications
Procedural pain 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Feeding tube complication 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Femur fracture 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Overdose 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Investigations
Liver function test abnormal 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Activated partial thromboplastin time prolonged 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Blood creatinine increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
International normalised ratio increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Prothrombin time prolonged 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Alanine aminotransferase increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Aspartate aminotransferase increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Metabolism and nutrition disorders
Dehydration 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 3/100 (3%)
Hypoglycaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Decreased appetite 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Hypokalaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Hyponatraemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Failure to thrive 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Hyperammonaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Musculoskeletal and connective tissue disorders
Back pain 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Flank pain 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Neck mass 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Metastases to rectum 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Metastasis 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Metastatic malignant melanoma 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Pancreatic carcinoma 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Colorectal cancer 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Malignant neoplasm progression 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Colorectal cancer metastatic 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Nervous system disorders
Headache 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Hepatic encephalopathy 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Psychiatric disorders
Delirium 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Mental status changes 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Renal and urinary disorders
Nephrolithiasis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Renal failure 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Renal failure acute 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Renal impairment 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Reproductive system and breast disorders
Menorrhagia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Vaginal haemorrhage 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Pleural effusion 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Acute respiratory distress syndrome 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Pulmonary embolism 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 3/100 (3%)
Respiratory failure 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Pneumonia aspiration 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Skin and subcutaneous tissue disorders
Rash maculo-papular 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Rash 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Urticaria 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Surgical and medical procedures
Hospitalisation 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Vascular disorders
Circulatory collapse 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Haemorrhage 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Hypertension 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Deep vein thrombosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Thrombosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Thrombophlebitis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Other (Not Including Serious) Adverse Events
Bosutinib 50 mg Bosutinib 100 mg Bosutinib 200 mg Bosutinib 300 mg Bosutinib 400 mg Bosutinib 500 mg Bosutinib 600 mg MTD lead-in RP2D 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/4 (100%) 4/4 (100%) 6/6 (100%) 7/7 (100%) 7/7 (100%) 7/7 (100%) 10/10 (100%) 6/6 (100%) 99/100 (99%)
Blood and lymphatic system disorders
Anaemia 1/4 (25%) 1/4 (25%) 0/6 (0%) 3/7 (42.9%) 3/7 (42.9%) 1/7 (14.3%) 2/10 (20%) 1/6 (16.7%) 20/100 (20%)
Lymphopenia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 3/10 (30%) 0/6 (0%) 3/100 (3%)
Thrombocytopenia 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 2/7 (28.6%) 1/7 (14.3%) 3/10 (30%) 0/6 (0%) 0/100 (0%)
Hypercoagulation 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Lymphadenopathy 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 0/100 (0%)
Leukopenia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Cardiac disorders
Tachycardia 1/4 (25%) 1/4 (25%) 1/6 (16.7%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Atrial fibrillation 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Sinus tachycardia 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Cardiac failure congestive 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 1/100 (1%)
Pericardial effusion 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Bradycardia 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Supraventricular tachycardia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Extrasystoles 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Palpitations 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Ear and labyrinth disorders
Tinnitus 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Eye disorders
Vision blurred 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 3/10 (30%) 0/6 (0%) 3/100 (3%)
Conjunctivitis 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Lacrimation increased 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Dry eye 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Eye oedema 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Visual acuity reduced 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Diplopia 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Orbital oedema 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Visual impairment 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Photophobia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Gastrointestinal disorders
Vomiting 2/4 (50%) 2/4 (50%) 0/6 (0%) 2/7 (28.6%) 4/7 (57.1%) 3/7 (42.9%) 9/10 (90%) 3/6 (50%) 51/100 (51%)
Nausea 3/4 (75%) 3/4 (75%) 3/6 (50%) 4/7 (57.1%) 5/7 (71.4%) 6/7 (85.7%) 8/10 (80%) 4/6 (66.7%) 65/100 (65%)
Diarrhoea 1/4 (25%) 0/4 (0%) 4/6 (66.7%) 4/7 (57.1%) 5/7 (71.4%) 5/7 (71.4%) 7/10 (70%) 4/6 (66.7%) 48/100 (48%)
Abdominal distension 2/4 (50%) 0/4 (0%) 2/6 (33.3%) 0/7 (0%) 1/7 (14.3%) 3/7 (42.9%) 3/10 (30%) 1/6 (16.7%) 12/100 (12%)
Abdominal pain 2/4 (50%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%) 3/7 (42.9%) 1/7 (14.3%) 5/10 (50%) 1/6 (16.7%) 27/100 (27%)
Constipation 1/4 (25%) 2/4 (50%) 2/6 (33.3%) 2/7 (28.6%) 3/7 (42.9%) 2/7 (28.6%) 2/10 (20%) 3/6 (50%) 15/100 (15%)
Eructation 0/4 (0%) 0/4 (0%) 3/6 (50%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Flatulence 2/4 (50%) 0/4 (0%) 2/6 (33.3%) 1/7 (14.3%) 1/7 (14.3%) 3/7 (42.9%) 2/10 (20%) 1/6 (16.7%) 15/100 (15%)
Dyspepsia 0/4 (0%) 0/4 (0%) 2/6 (33.3%) 0/7 (0%) 0/7 (0%) 2/7 (28.6%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Abdominal pain lower 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Abdominal pain upper 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 12/100 (12%)
Ascites 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 7/100 (7%)
Abdominal discomfort 0/4 (0%) 1/4 (25%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Cheilitis 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Dental caries 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Dysphagia 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 4/100 (4%)
Gastritis 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Stomatitis 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 2/100 (2%)
Toothache 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Gastrointestinal disorder 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Gastrooesophageal reflux disease 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 1/6 (16.7%) 2/100 (2%)
Haemorrhoids 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 1/100 (1%)
Dry mouth 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Gastrointestinal haemorrhage 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Gastrointestinal oedema 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Melaena 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Small intestinal obstruction 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Haematemesis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Haematochezia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Impaired gastric emptying 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Lip dry 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
General disorders
Fatigue 3/4 (75%) 3/4 (75%) 4/6 (66.7%) 4/7 (57.1%) 5/7 (71.4%) 4/7 (57.1%) 8/10 (80%) 5/6 (83.3%) 47/100 (47%)
Oedema peripheral 2/4 (50%) 1/4 (25%) 3/6 (50%) 0/7 (0%) 3/7 (42.9%) 2/7 (28.6%) 2/10 (20%) 1/6 (16.7%) 14/100 (14%)
Pyrexia 2/4 (50%) 1/4 (25%) 0/6 (0%) 1/7 (14.3%) 3/7 (42.9%) 0/7 (0%) 3/10 (30%) 2/6 (33.3%) 13/100 (13%)
Asthenia 1/4 (25%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 5/100 (5%)
Early satiety 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Catheter thrombosis 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Chest pain 0/4 (0%) 1/4 (25%) 1/6 (16.7%) 1/7 (14.3%) 0/7 (0%) 1/7 (14.3%) 2/10 (20%) 0/6 (0%) 6/100 (6%)
Chills 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 6/100 (6%)
Chest discomfort 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 1/6 (16.7%) 1/100 (1%)
Crepitations 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Gait disturbance 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Nodule 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Pain 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 4/100 (4%)
Catheter site related reaction 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Local swelling 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Oedema 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 6/100 (6%)
Temperature intolerance 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Feeling hot 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Localised oedema 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 11/100 (11%)
Infections and infestations
Urinary tract infection 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 10/100 (10%)
Bronchitis 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Influenza 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 1/100 (1%)
Laryngitis 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Oral herpes 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Postoperative wound infection 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Skin infection 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Nasopharyngitis 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Viral pharyngitis 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Pneumonia 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 5/100 (5%)
Septic shock 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Sinusitis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Staphylococcal infection 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Upper respiratory tract infection 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 5/100 (5%)
Injury, poisoning and procedural complications
Incision site pain 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Post procedural complication 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Procedural pain 1/4 (25%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Procedural site reaction 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Excoriation 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Overdose 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 1/100 (1%)
Spinal compression fracture 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Arthropod bite 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Contrast media reaction 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Drug toxicity 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Fall 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 2/100 (2%)
Transfusion reaction 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Wound 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Investigations
Weight decreased 0/4 (0%) 0/4 (0%) 2/6 (33.3%) 3/7 (42.9%) 3/7 (42.9%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 16/100 (16%)
Aspartate aminotransferase increased 0/4 (0%) 0/4 (0%) 2/6 (33.3%) 1/7 (14.3%) 0/7 (0%) 2/7 (28.6%) 2/10 (20%) 0/6 (0%) 16/100 (16%)
Breath sounds abnormal 0/4 (0%) 1/4 (25%) 2/6 (33.3%) 0/7 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Alanine aminotransferase increased 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 1/7 (14.3%) 2/7 (28.6%) 3/10 (30%) 0/6 (0%) 14/100 (14%)
Blood bilirubin increased 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Electrocardiogram QT prolonged 1/4 (25%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Electrocardiogram T wave abnormal 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Blood alkaline phosphatase increased 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 14/100 (14%)
Pulmonary function test decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
White blood cell count increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 0/100 (0%)
Activated partial thromboplastin time prolonged 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 4/100 (4%)
Blood albumin decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Blood creatinine increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 12/100 (12%)
Blood phosphorus decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Body temperature increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Haemoglobin decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 10/100 (10%)
International normalised ratio increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Urine analysis abnormal 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
White blood cells urine positive 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Blood phosphorus increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Blood urea decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Cardiac murmur 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Gamma-glutamyltransferase increased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 4/100 (4%)
Platelet count decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 3/100 (3%)
Urine output decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Metabolism and nutrition disorders
Anorexia 3/4 (75%) 1/4 (25%) 2/6 (33.3%) 2/7 (28.6%) 4/7 (57.1%) 1/7 (14.3%) 5/10 (50%) 5/6 (83.3%) 43/100 (43%)
Hypokalaemia 1/4 (25%) 3/4 (75%) 0/6 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/7 (0%) 3/10 (30%) 1/6 (16.7%) 6/100 (6%)
Dehydration 2/4 (50%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 3/10 (30%) 2/6 (33.3%) 21/100 (21%)
Hypomagnesaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Hypocalcaemia 1/4 (25%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Decreased appetite 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 2/10 (20%) 1/6 (16.7%) 12/100 (12%)
Hyperglycaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 8/100 (8%)
Hypoglycaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 5/100 (5%)
Hyponatraemia 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 6/100 (6%)
Hypercalcaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Hyperkalaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 5/100 (5%)
Hypernatraemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Hypovolaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Lactic acidosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Metabolic alkalosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Hypoalbuminaemia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 5/100 (5%)
Musculoskeletal and connective tissue disorders
Back pain 0/4 (0%) 0/4 (0%) 2/6 (33.3%) 1/7 (14.3%) 2/7 (28.6%) 2/7 (28.6%) 0/10 (0%) 4/6 (66.7%) 12/100 (12%)
Arthralgia 2/4 (50%) 1/4 (25%) 0/6 (0%) 1/7 (14.3%) 2/7 (28.6%) 2/7 (28.6%) 1/10 (10%) 2/6 (33.3%) 9/100 (9%)
Musculoskeletal chest pain 2/4 (50%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 5/100 (5%)
Pain in extremity 2/4 (50%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 1/7 (14.3%) 1/7 (14.3%) 2/10 (20%) 2/6 (33.3%) 8/100 (8%)
Flank pain 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 1/7 (14.3%) 0/10 (0%) 2/6 (33.3%) 2/100 (2%)
Joint swelling 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Muscle spasms 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Musculoskeletal pain 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 3/100 (3%)
Neck mass 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Neck pain 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 2/100 (2%)
Muscular weakness 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Myalgia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Joint range of motion decreased 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix neoplasm 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Haemangioma 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Basal cell carcinoma 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Melanocytic naevus 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Metastases to central nervous system 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Nervous system disorders
Dizziness 3/4 (75%) 1/4 (25%) 2/6 (33.3%) 4/7 (57.1%) 0/7 (0%) 2/7 (28.6%) 3/10 (30%) 2/6 (33.3%) 11/100 (11%)
Headache 1/4 (25%) 0/4 (0%) 2/6 (33.3%) 2/7 (28.6%) 3/7 (42.9%) 1/7 (14.3%) 5/10 (50%) 1/6 (16.7%) 16/100 (16%)
Cervical cord compression 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Hypoaesthesia 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Migraine 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Neuralgia 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Somnolence 1/4 (25%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 2/100 (2%)
Amnesia 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Ataxia 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 1/100 (1%)
Dysgeusia 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 5/100 (5%)
Neuropathy peripheral 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 3/100 (3%)
Paraesthesia 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Sinus headache 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Transient ischaemic attack 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Convulsion 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Memory impairment 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Peripheral sensory neuropathy 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Lethargy 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Psychiatric disorders
Insomnia 2/4 (50%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%) 1/7 (14.3%) 6/7 (85.7%) 2/10 (20%) 2/6 (33.3%) 11/100 (11%)
Depression 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 1/7 (14.3%) 1/7 (14.3%) 4/10 (40%) 2/6 (33.3%) 3/100 (3%)
Anxiety 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 1/10 (10%) 2/6 (33.3%) 4/100 (4%)
Confusional state 0/4 (0%) 1/4 (25%) 0/6 (0%) 2/7 (28.6%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 4/100 (4%)
Agitation 0/4 (0%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 2/100 (2%)
Restlessness 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Anger 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Mood altered 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Mental status changes 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 3/100 (3%)
Renal and urinary disorders
Haematuria 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Urinary incontinence 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Bladder spasm 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Dysuria 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 3/100 (3%)
Micturition urgency 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Hydronephrosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Pollakiuria 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Renal failure 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Glycosuria 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Renal failure acute 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Urinary hesitation 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Reproductive system and breast disorders
Oedema genital 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Endometriosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Haemorrhagic ovarian cyst 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Menstruation irregular 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Ovarian cyst 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Pelvic pain 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 0/4 (0%) 1/4 (25%) 1/6 (16.7%) 3/7 (42.9%) 3/7 (42.9%) 0/7 (0%) 3/10 (30%) 2/6 (33.3%) 23/100 (23%)
Dyspnoea exertional 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 2/6 (33.3%) 0/100 (0%)
Epistaxis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 2/6 (33.3%) 0/100 (0%)
Atelectasis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Cough 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 2/7 (28.6%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 13/100 (13%)
Dysphonia 0/4 (0%) 1/4 (25%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Hiccups 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 4/100 (4%)
Hypoxia 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 2/100 (2%)
Oropharyngeal pain 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 7/100 (7%)
Pleural effusion 1/4 (25%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 4/100 (4%)
Pneumothorax 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Haemoptysis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Nasal congestion 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 1/100 (1%)
Skin and subcutaneous tissue disorders
Rash 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 2/7 (28.6%) 2/10 (20%) 1/6 (16.7%) 22/100 (22%)
Alopecia 1/4 (25%) 1/4 (25%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Hyperhidrosis 0/4 (0%) 1/4 (25%) 1/6 (16.7%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 5/100 (5%)
Dry skin 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/10 (10%) 1/6 (16.7%) 2/100 (2%)
Ecchymosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 0/100 (0%)
Erythema 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/7 (14.3%) 1/10 (10%) 1/6 (16.7%) 2/100 (2%)
Periorbital oedema 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Petechiae 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 1/100 (1%)
Rash follicular 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Rash macular 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 1/100 (1%)
Skin discolouration 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Skin exfoliation 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Dermatitis acneiform 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Night sweats 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Rash maculo-papular 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 0/100 (0%)
Rash pruritic 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 1/7 (14.3%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Rash erythematous 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 1/100 (1%)
Skin hyperpigmentation 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Skin lesion 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Vascular disorders
Hypertension 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 0/100 (0%)
Pallor 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 2/7 (28.6%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 0/100 (0%)
Flushing 0/4 (0%) 1/4 (25%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 0/10 (0%) 1/6 (16.7%) 0/100 (0%)
Hot flush 1/4 (25%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 1/10 (10%) 1/6 (16.7%) 1/100 (1%)
Lymphoedema 0/4 (0%) 0/4 (0%) 1/6 (16.7%) 0/7 (0%) 0/7 (0%) 0/7 (0%) 2/10 (20%) 0/6 (0%) 1/100 (1%)
Deep vein thrombosis 0/4 (0%) 0/4 (0%) 0/6 (0%) 0/7 (0%) 1/7 (14.3%) 0/7 (0%) 0/10 (0%) 0/6 (0%) 2/100 (2%)
Hypotension 0/4 (0%) 0/4 (0%) 0/6 (0%) 1/7 (14.3%) 0/7 (0%) 0/7 (0%) 1/10 (10%) 0/6 (0%) 5/100 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00195260
Other Study ID Numbers:
  • 3160A1-100
  • B1871012
First Posted:
Sep 19, 2005
Last Update Posted:
Feb 11, 2013
Last Verified:
Jan 1, 2013