Trial Outcomes & Findings for Gemcitabine Plus Albumin-bound Paclitaxel In Patients With Advanced Metastatic Pancreatic Cancer (NCT NCT00398086)

NCT ID: NCT00398086

Last Updated: 2019-11-22

Results Overview

A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3: * Grade 4 neutropenia lasting \>3 days in the absence of growth factor support; * Grade 4 neutropenia associated with fever \>38.5°C; * Any other Grade 4 hematological toxicity; * Grade 3 thrombocytopenia with hemorrhage; * Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen; * Any other Grade 3 or higher non-hematological toxicity attributable to the study drug, excluding alopecia and fatigue.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 67 participants
• Primary outcome timeframe: Cycle 1 (Days 1-28)
• Results posted on: 2019-11-22

Participant Flow

Enrollment was initiated in November 2006 and completed in September 2008. Sixty-seven patients were enrolled at four sites in the US.

In Phase 1, patients were assigned sequentially to one of the three potential dose levels based on the dose cohort currently enrolling patients (a total of 30 patients). After the maximum tolerated dose (MTD) was determined, all subsequent patients were enrolled at that dose level in Phase 2 (37 patients).

Participant milestones

Measure	100 mg/m^2 Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Overall Study STARTED	20	44	3
Overall Study Phase 1, Dose Escalation Population	20	7	3
Overall Study COMPLETED	11	21	1
Overall Study NOT COMPLETED	9	23	2

Reasons for withdrawal

Measure	100 mg/m^2 Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Overall Study Unacceptable Toxicity	2	8	2
Overall Study Adverse Event	1	4	0
Overall Study Physician Decision	1	4	0
Overall Study Withdrawal by Subject	5	7	0

Baseline Characteristics

Gemcitabine Plus Albumin-bound Paclitaxel In Patients With Advanced Metastatic Pancreatic Cancer

Baseline characteristics by cohort

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.	Total n=67 Participants Total of all reporting groups
Age, Continuous	62.0 years n=5 Participants	61.5 years n=7 Participants	69.0 years n=5 Participants	62.0 years n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	25 Participants n=7 Participants	1 Participants n=5 Participants	35 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	19 Participants n=7 Participants	2 Participants n=5 Participants	32 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized Black, of African Heritage	0 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized White, Non-Hispanic, and Non-Latino	16 participants n=5 Participants	37 participants n=7 Participants	1 participants n=5 Participants	54 participants n=4 Participants
Race/Ethnicity, Customized White, Hispanic, or Latino	2 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	8 participants n=4 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment United States	20 participants n=5 Participants	44 participants n=7 Participants	3 participants n=5 Participants	67 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully Active)	9 participants n=5 Participants	22 participants n=7 Participants	2 participants n=5 Participants	33 participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but Ambulatory)	11 participants n=5 Participants	22 participants n=7 Participants	1 participants n=5 Participants	34 participants n=4 Participants
Histology of Primary Diagnosis: Adenocarcinoma	20 participants n=5 Participants	44 participants n=7 Participants	3 participants n=5 Participants	67 participants n=4 Participants
Time from First Documented Metastasis/Relapse to Study Entry	0.8 months n=5 Participants	0.7 months n=7 Participants	0.3 months n=5 Participants	0.7 months n=4 Participants
Current Site(s) of Metastasis/Relapse Skin/Soft Tissue	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Supraclavicular Nodes	0 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Axilla	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Bone	1 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Lung/Thoracic	5 participants n=5 Participants	18 participants n=7 Participants	1 participants n=5 Participants	24 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Liver	11 participants n=5 Participants	33 participants n=7 Participants	2 participants n=5 Participants	46 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Abdomen/Peritoneum	16 participants n=5 Participants	37 participants n=7 Participants	1 participants n=5 Participants	54 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Pelvis	1 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Current Site(s) of Metastasis/Relapse Other	8 participants n=5 Participants	6 participants n=7 Participants	0 participants n=5 Participants	14 participants n=4 Participants
Dominant Current Site of Metastasis/Relapse Visceral	19 participants n=5 Participants	44 participants n=7 Participants	3 participants n=5 Participants	66 participants n=4 Participants
Dominant Current Site of Metastasis/Relapse Non-visceral	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Days 1-28)

Population: Phase 1 treated population

A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3:

• Grade 4 neutropenia lasting >3 days in the absence of growth factor support;
• Grade 4 neutropenia associated with fever >38.5°C;
• Any other Grade 4 hematological toxicity;
• Grade 3 thrombocytopenia with hemorrhage;
• Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen;
• Any other Grade 3 or higher non-hematological toxicity attributable to the study drug, excluding alopecia and fatigue.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=7 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Number of Participants With Dose-limiting Toxicities	4 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Up to 25 months

Population: Treated patients: all enrolled patients who received at least one dose of study drug.

An AE was any untoward medical occurrence, not necessarily having a causal relationship with the patient's treatment, that began or worsened in grade after the start of study drug through 30 days after the last dose.

A serious AE (SAE) is any untoward medical occurrence that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

Treatment-related AEs (TRAEs) include those assessed by the Investigator as possibly, probably, or definitely related to study treatment.

Severity was graded according to the NCI CTCAE based on the following: Grade 1- Mild; Grade 2 -Moderate; Grade 3 - Severe; Grade 4 - Life-threatening or disabling; Grade 5 - Death related to AE.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Number of Participants With Adverse Events (AE) Patients with at least 1 AE	20 participants	44 participants	3 participants
Number of Participants With Adverse Events (AE) At least 1 grade 3 or higher AE	15 participants	42 participants	3 participants
Number of Participants With Adverse Events (AE) At least 1 treatment-related AE	18 participants	42 participants	3 participants
Number of Participants With Adverse Events (AE) At least 1 treatment-related grade 3 to 5 AE	11 participants	38 participants	3 participants
Number of Participants With Adverse Events (AE) Patients with at least 1 SAE	10 participants	24 participants	1 participants
Number of Participants With Adverse Events (AE) Patients with at least 1 treatment-related SAE	4 participants	12 participants	1 participants
Number of Participants With Adverse Events (AE) At least 1 AE and drug permanently discontinued	3 participants	12 participants	2 participants
Number of Participants With Adverse Events (AE) At least 1 TRAE and drug permanently discontinued	2 participants	8 participants	2 participants
Number of Participants With Adverse Events (AE) At least 1 dose reduction due to TRAE	4 participants	10 participants	1 participants
Number of Participants With Adverse Events (AE) At least 1 dose interruption due to AE	1 participants	0 participants	0 participants
Number of Participants With Adverse Events (AE) At least 1 treatment-related AE dose interruption	1 participants	0 participants	0 participants
Number of Participants With Adverse Events (AE) At least 1 treatment-emergent dose delay due to AE	14 participants	27 participants	3 participants
Number of Participants With Adverse Events (AE) At least 1 treatment-related dose delay due to AE	13 participants	27 participants	3 participants
Number of Participants With Adverse Events (AE) At least 1 AE resulting in death	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Treated patients

Overall Response is defined as the percent of participants who achieve an objective confirmed complete (CR) or partial response (PR). Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, assessed by an Independent Radiological Reviewer.

CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers.

PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation and no new non-target lesions and/or unequivocal progression of existing non-target lesions. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Percentage of Participants Who Achieved an Objective Confirmed Overall Response	25 percentage of participants Interval 8.7 to 49.1	39 percentage of participants Interval 24.2 to 53.0	0 percentage of participants Could not be calculated as no participants responded in this group

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Treated patients

Disease control is defined as participants with Stable Disease for at least 16 weeks, or confirmed complete or partial overall response, based on RECIST guidelines and assessed by an Independent Radiological Reviewer.

Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease, and no new non-target lesions or unequivocal progression of existing non-target lesions. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Percentage of Participants With Disease Control	55 percentage of participants Interval 33.2 to 76.8	55 percentage of participants Interval 39.8 to 69.3	33 percentage of participants Interval 0.8 to 90.6

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Treated patients

Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first, assessed by an Independent Radiological Reviewer. Participants who do not have disease progression or have not died were censored at the last known time that the participant was progression free. Progression-free survival was summarized using Kaplan-Meier methods.

Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Progression-free Survival	6.1 months Interval 3.7 to Could not be estimated due to low number of events.	6.9 months Interval 4.8 to 9.2	1.6 months Interval 0.5 to 10.0

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Treated patients with an overall confirmed Complete Response or Partial Response.

Duration of response was assessed by progression-free survival for participants who achieved a confirmed Complete Response or Partial Response, assessed by an Independent Radiological Reviewer.

Outcome measures

Measure	100 mg/m^2 n=5 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=17 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Duration of Response	NA months Interval 2.4 to Not estimable due to the low number of events.	7.3 months Interval 5.5 to 21.9	—

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Treated patients

Overall survival was defined as the time from the date of first dose of study drug to the date of patient death from all causes. Participants who did not die were censored at the last known time the patient was alive. Patient survival was summarized using Kaplan-Meier methods.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Overall Survival	9.3 months Interval 6.6 to 11.9	12.2 months Interval 8.9 to 17.9	6.1 months Interval 0.5 to 17.9

SECONDARY outcome

Timeframe: During the treatment phase, up to a maximum of 24 months.

Population: Treated patients with available data

The maximal degree of myelosuppression was assessed by the overall nadir of absolute neutrophil count (ANC), white blood cell count and platelet count based on clinical laboratory measurements.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=43 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Maximal Degree of Myelosuppression Absolute neutrophil count	1.38 x10^9/L Standard Deviation 1.541	0.96 x10^9/L Standard Deviation 1.446	0.47 x10^9/L Standard Deviation 0.460
Maximal Degree of Myelosuppression White blood cell count	2.69 x10^9/L Standard Deviation 1.734	2.18 x10^9/L Standard Deviation 1.849	1.52 x10^9/L Standard Deviation 1.484
Maximal Degree of Myelosuppression Platelet count	120.3 x10^9/L Standard Deviation 79.02	88.3 x10^9/L Standard Deviation 62.10	58.7 x10^9/L Standard Deviation 48.64

SECONDARY outcome

Timeframe: During the treatment phase, up to a maximum of 24 months.

Population: Treated patients with available data

The maximal degree of anemia (and myelosuppression) was assessed by the overall (any time after first dose of study drug) nadir of hemoglobin levels based on clinical laboratory measurements.

Outcome measures

Measure	100 mg/m^2 n=20 Participants Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=43 Participants Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 Participants Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Maximal Degree of Anemia	95.1 g/L Standard Deviation 12.85	91.8 g/L Standard Deviation 10.43	95.3 g/L Standard Deviation 15.37

Adverse Events

100 mg/m^2

Serious events: 10 serious events

Other events: 20 other events

Deaths: 0 deaths

125 mg/m^2

Serious events: 24 serious events

Other events: 44 other events

Deaths: 0 deaths

150 mg/m^2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	100 mg/m^2 n=20 participants at risk Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 participants at risk Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 participants at risk Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Infections and infestations Pneumonia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Bacteraemia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Neutropenic sepsis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Abdominal wall abscess	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Cellulitis	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Clostridium difficile colitis	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Endocarditis	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Infection	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Sepsis	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Urinary tract infection	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Diarrhoea	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Intestinal obstruction	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Ascites	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Duodenal obstruction	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Enterocutaneous fistula	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Ileus	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Ileus paralytic	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Nausea	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Obstruction gastric	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Pyrexia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Pain	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Hernia obstructive	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Febrile neutropenia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Pancytopenia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Anaemia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Neutropenia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Loss of consciousness	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Cerebrovascular accident	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Convulsion	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Migraine with aura	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Sedation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Syncope	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Dehydration	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Cardiac disorders Atrial fibrillation	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Cardiac disorders Supraventricular tachycardia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Hepatobiliary disorders Bile duct obstruction	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Hepatobiliary disorders Cholangitis	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Hip fracture	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Medical device complication	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Muscular weakness	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Mental status changes	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Hydronephrosis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Ureteric obstruction	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).

Other adverse events

Measure	100 mg/m^2 n=20 participants at risk Participants received albumin-bound paclitaxel 100 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity.	125 mg/m^2 n=44 participants at risk Participants received albumin-bound paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity.	150 mg/m^2 n=3 participants at risk Participants received albumin-bound paclitaxel 150 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity.
Nervous system disorders Head discomfort	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Headache	35.0% 7/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	20.5% 9/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Hypoaesthesia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Migraine	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Neuropathy peripheral	25.0% 5/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	65.9% 29/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Paraesthesia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Peripheral motor neuropathy	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Peripheral nerve palsy	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Peripheral sensory neuropathy	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Sinus headache	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Somnolence	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Syncope	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Agitation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Ear and labyrinth disorders Ear pain	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Ear and labyrinth disorders Hypoacusis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Endocrine disorders Steroid withdrawal syndrome	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Blepharitis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Conjunctival haemorrhage	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Conjunctivitis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Diplopia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Dry eye	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Eye swelling	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Vision blurred	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Eye disorders Visual impairment	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Abdominal distension	20.0% 4/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	20.5% 9/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Cognitive disorder	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Abdominal pain	35.0% 7/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	38.6% 17/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Dizziness	40.0% 8/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	29.5% 13/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Abdominal pain lower	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Dysarthria	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Abdominal pain upper	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Colitis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Constipation	30.0% 6/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	47.7% 21/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Diarrhoea	35.0% 7/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	52.3% 23/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Dry mouth	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Dyspepsia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	11.4% 5/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Dysphagia	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Eructation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Faecal incontinence	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Flatulence	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Gastrooesophageal reflux disease	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Dysgeusia	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	36.4% 16/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Haemorrhoids	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Hiatus hernia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Melaena	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Mouth ulceration	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Nausea	40.0% 8/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	65.9% 29/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Anaemia	60.0% 12/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	68.2% 30/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Bone marrow failure	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Leukopenia	20.0% 4/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	40.9% 18/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Neutropenia	50.0% 10/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	56.8% 25/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Blood and lymphatic system disorders Thrombocytopenia	25.0% 5/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	59.1% 26/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Cardiac disorders Atrial fibrillation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Cardiac disorders Bradycardia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Cardiac disorders Palpitations	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Cardiac disorders Tachycardia	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Cardiac disorders Ventricular extrasystoles	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Odynophagia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Oral mucosal erythema	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Oral pain	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Retching	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Stomatitis	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Gastrointestinal disorders Vomiting	25.0% 5/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	45.5% 20/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Asthenia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	15.9% 7/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Catheter related complication	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Catheter site inflammation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Chest discomfort	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Chest pain	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Chills	25.0% 5/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	22.7% 10/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Fatigue	75.0% 15/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	88.6% 39/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	100.0% 3/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Influenza like illness	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Infusion site pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Injection site extravasation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Local swelling	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Malaise	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Mucosal dryness	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Mucosal inflammation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	25.0% 11/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Oedema peripheral	35.0% 7/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	61.4% 27/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Pain	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
General disorders Pyrexia	40.0% 8/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	45.5% 20/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Hepatobiliary disorders Bile duct obstruction	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Hepatobiliary disorders Hyperbilirubinaemia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Hepatobiliary disorders Portal vein thrombosis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Immune system disorders Seasonal allergy	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Candidiasis	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	11.4% 5/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Cellulitis	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	11.4% 5/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Folliculitis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Fungal infection	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Infection	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Lobar pneumonia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Localised infection	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Oral candidiasis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Pneumonia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Rash pustular	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Sinusitis	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Upper respiratory tract infection	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Infections and infestations Urinary tract infection	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	15.9% 7/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Contusion	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Incision site complication	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Medical device pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Nail avulsion	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Post-traumatic pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Procedural pain	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Procedural site reaction	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Stent occlusion	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Injury, poisoning and procedural complications Sunburn	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Alanine aminotransferase increased	30.0% 6/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Aspartate aminotransferase increased	25.0% 5/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Blood albumin decreased	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Blood alkaline phosphatase increased	20.0% 4/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Blood creatinine increased	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Blood urine present	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Neutrophil count decreased	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	20.5% 9/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Platelet count decreased	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Weight decreased	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	18.2% 8/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Investigations Weight increased	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Decreased appetite	45.0% 9/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	50.0% 22/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Dehydration	30.0% 6/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	27.3% 12/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Hypoalbuminaemia	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Hypocalcaemia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Hypokalaemia	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	27.3% 12/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Hypomagnesaemia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Metabolism and nutrition disorders Hyponatraemia	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	22.7% 10/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Back pain	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	11.4% 5/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Bone pain	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Bunion	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Flank pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Joint contracture	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Muscular weakness	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	22.7% 10/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Neck pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Musculoskeletal and connective tissue disorders Pain in extremity	20.0% 4/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	20.5% 9/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Balance disorder	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Nervous system disorders Burning sensation	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Anxiety	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	29.5% 13/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Confusional state	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Depressed mood	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Depression	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	18.2% 8/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Insomnia	35.0% 7/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	29.5% 13/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Psychiatric disorders Restlessness	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Bladder spasm	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Dysuria	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Haematuria	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Incontinence	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Proteinuria	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Renal pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Urinary incontinence	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Renal and urinary disorders Urinary tract disorder	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Reproductive system and breast disorders Breast pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Cough	25.0% 5/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	29.5% 13/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	35.0% 7/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	25.0% 11/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	9.1% 4/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Epistaxis	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	22.7% 10/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Hypoxia	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Lung infiltration	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	13.6% 6/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	13.6% 6/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Respiratory, thoracic and mediastinal disorders Wheezing	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Alopecia	75.0% 15/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	79.5% 35/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Decubitus ulcer	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Dry skin	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Erythema	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	22.7% 10/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Hyperhidrosis	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	11.4% 5/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Nail discolouration	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Nail disorder	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Night sweats	20.0% 4/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Pruritus	25.0% 5/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	22.7% 10/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Rash	35.0% 7/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	50.0% 22/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	66.7% 2/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Skin hyperpigmentation	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	2.3% 1/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Skin and subcutaneous tissue disorders Urticaria	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Surgical and medical procedures Biliary drainage	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Vascular disorders Deep vein thrombosis	0.00% 0/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	11.4% 5/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Vascular disorders Flushing	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	4.5% 2/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Vascular disorders Hypertension	5.0% 1/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	6.8% 3/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Vascular disorders Hypotension	15.0% 3/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	11.4% 5/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	0.00% 0/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).
Vascular disorders Orthostatic hypotension	10.0% 2/20 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	13.6% 6/44 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).	33.3% 1/3 • Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).

Additional Information

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Celgene Corporation

Phone: 1-888-260-1599

Email: clinicaltrialdisclosure@celgene.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institution may publish the results of its findings if a multicenter publication is not forthcoming within 18 months after study completion. Institution shall provide Celgene with a copy of the papers prior to their submission; Celgene shall complete its review within 30 days after receipt. Upon Celgene's request, proposed publication or presentation can be delayed up to 60 additional days to enable Celgene to secure adequate intellectual property protection of patentable material.
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Restriction type: OTHER