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Trial record 61 of 183 for:    carfilzomib OR pr-171

Phase 1b Multicenter Study of Carfilzomib With Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00603447
Recruitment Status : Completed
First Posted : January 29, 2008
Results First Posted : June 3, 2015
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsed Multiple Myeloma
Interventions Drug: Carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
Enrollment 84
Recruitment Details This was an open-label study of carfilzomib (CFZ) given in combination with lenalidomide (LEN) and low-dose dexamethasone (DEX) in patients with relapsed multiple myeloma. The study consisted of a dose-escalation portion and an expansion portion. Participants were treated until disease progression (PD) or unacceptable toxicity.
Pre-assignment Details In the dose-escalation portion, participants were enrolled in sequential cohorts to determine the maximum tolerated doses (MTD) of carfilzomib and lenalidomide. In the expansion portion either the MTD or the maximum planned dose (MPD) from Cohort 6 (if no MTD was determined) was administered to gain additional safety and efficacy information.
Arm/Group Title 1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg 7: CFZ 20/27 mg/m² + LEN 25 mg
Hide Arm/Group Description Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 10 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 15 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. In the Expansion portion, treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Period Title: Overall Study
Started 6 6 8 6 6 8 44
Completed 6 [1] 3 [1] 6 [1] 4 [1] 1 [1] 6 [1] 20 [1]
Not Completed 0 3 2 2 5 2 24
Reason Not Completed
Adverse Event             0             1             1             2             1             2             10
Other             0             0             1             0             3             0             13
Withdrew Consent             0             2             0             0             1             0             1
[1]
Participants on-going as of 08 May 2013, discontinued due to PD or completed treatment per protocol.
Arm/Group Title 1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg 7: CFZ 20/27 mg/m² + LEN 25 mg Total
Hide Arm/Group Description Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 10 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 15 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. In the Expansion portion, treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion. Total of all reporting groups
Overall Number of Baseline Participants 6 6 8 6 6 8 44 84
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 8 participants 6 participants 6 participants 8 participants 44 participants 84 participants
64.7  (6.65) 64.2  (12.11) 55.4  (7.74) 61.7  (6.68) 57.7  (9.31) 65.4  (7.85) 62.4  (10.75) 61.9  (9.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 8 participants 6 participants 6 participants 8 participants 44 participants 84 participants
Female
1
  16.7%
4
  66.7%
3
  37.5%
4
  66.7%
3
  50.0%
3
  37.5%
18
  40.9%
36
  42.9%
Male
5
  83.3%
2
  33.3%
5
  62.5%
2
  33.3%
3
  50.0%
5
  62.5%
26
  59.1%
48
  57.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 8 participants 6 participants 6 participants 8 participants 44 participants 84 participants
African American 0 2 1 2 1 0 3 9
Asian/Pacific Islander 0 1 0 0 0 0 2 3
Caucasian 6 3 7 2 5 7 34 64
Hispanic 0 0 0 2 0 1 4 7
Other 0 0 0 0 0 0 1 1
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 8 participants 6 participants 6 participants 8 participants 44 participants 84 participants
0 (Fully active) 2 0 3 1 2 2 23 33
1 (Restrictive but ambulatory) 4 5 5 5 4 6 17 46
2 (Ambulatory but unable to work) 0 1 0 0 0 0 4 5
[1]
Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, no self-care, confined to bed or chair.
Time Since Diagnosis  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 8 participants 6 participants 6 participants 8 participants 44 participants 84 participants
3.3
(2 to 4)
2.4
(2 to 5)
3.9
(2 to 15)
2.8
(0 to 9)
3.5
(1 to 22)
4.3
(1 to 12)
2.8
(0 to 16)
3.1
(0 to 22)
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description

Treatment-related are those AEs with possible or probable relationship to carfilzomib, lenalidomide or dexamethasone as assessed by the Investigator. The severity of each adverse event was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0, per the following: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.

Serious adverse events were defined as AEs meeting one of the following: death, life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in the offspring of an exposed participant, important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above, or pregnancy or suspected pregnancy.

Time Frame From the first dose of study drug until 30 days after the last dose; 1 to 52 months, with an average of 12 months.
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Hide Analysis Population Description
Safety population consisting of all treated participants
Arm/Group Title 1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg 7: CFZ 20/27 mg/m² + LEN 25 mg
Hide Arm/Group Description:
Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 10 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 15 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
In the Expansion portion, treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Overall Number of Participants Analyzed 6 6 8 6 6 8 44
Measure Type: Number
Unit of Measure: participants
Any adverse event 6 6 8 6 6 8 44
Treatment-related adverse event 4 5 8 4 6 8 43
Grade 3 or higher adverse event 5 6 8 6 6 8 41
Treatment-related Grade 3 or higher adverse event 1 4 7 4 6 8 38
Serious adverse event 3 3 4 4 3 6 22
AE leading to discontinuation of any study drug 1 1 3 4 2 3 18
AE leading to discontinuation of carfilzomib 0 0 1 2 1 1 9
Deaths within 30 days of last dose of study drug 0 0 0 0 0 0 3
2.Primary Outcome
Title Number of Participants With Dose-limiting Toxicities
Hide Description

Dose-limiting toxicity was defined as any of the following events assessed as related to carfilzomib, lenalidomide, or dexamethasone: Nonhematologic

  • ≥ Grade 2 neuropathy with pain
  • ≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, diarrhea, hyperglycemia due to dexamethasone, and rash due to lenalidomide)
  • ≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal supportive therapy
  • ≥ Grade 4 fatigue persisting > 7 days
  • Treatment delay for toxicity > 21 days

Hematologic

  • Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) > 7 days
  • Febrile neutropenia (ANC < 1,000/mm³ with fever ≥ 38.3ºC)
  • Grade 4 thrombocytopenia (platelets < 25,000/mm³) for > 7 days despite holding treatment, or Grade 3 or 4 thrombocytopenia associated with bleeding
  • Treatment delay for toxicity > 21 days.

The maximum-tolerated dose was defined as the dose level below which a drug-related DLT was observed in ≥ 33% of participants in a cohort.

Time Frame Cycle 1, 28 days
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Hide Analysis Population Description
Safety population for the dose escalation portion of the study
Arm/Group Title 1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg
Hide Arm/Group Description:
Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 10 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 15 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator’s discretion.
Overall Number of Participants Analyzed 6 6 8 6 6 8
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 1
Time Frame From the first dose of study drug until 30 days after the last dose; 1 to 52 months, with an average of 12 months.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title 1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg 7: CFZ 20/27 mg/m² + LEN 25 mg
Hide Arm/Group Description Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 10 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 15 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 15 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 20 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15, and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion. Treatment during Cycles 1 through 12 consisted of carfilzomib 20 mg/m² on Days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion. Treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion. In the Expansion portion, treatment consisted of carfilzomib 20 mg/m² on Days 1 and 2 of Cycle 1, followed by 27 mg/m² for the remainder of treatment (Days 8, 9, 15, and 16 of Cycle 1 and Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles); lenalidomide 25 mg on Days 1 to 21; and 40 mg dexamethasone on Days 1, 8, and 15 and 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion.
All-Cause Mortality
1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg 7: CFZ 20/27 mg/m² + LEN 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg 7: CFZ 20/27 mg/m² + LEN 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/6 (50.00%)   3/6 (50.00%)   4/8 (50.00%)   4/6 (66.67%)   3/6 (50.00%)   6/8 (75.00%)   22/44 (50.00%) 
Blood and lymphatic system disorders               
Anaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Febrile neutropenia  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Neutropenia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Thrombocytopenia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Cardiac disorders               
Acute myocardial infarction  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Atrial fibrillation  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Bradycardia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Coronary artery disease  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Myocardial infarction  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Sick sinus syndrome  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Gastrointestinal disorders               
Colonic stenosis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Diarrhoea  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Gastrointestinal haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Small intestinal obstruction  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
General disorders               
Death  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Disease progression  1  2/6 (33.33%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Face oedema  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Pain  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Pyrexia  1  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Infections and infestations               
Abscess jaw  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Bronchitis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Bronchitis viral  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Cellulitis  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Infection  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Influenza  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/8 (25.00%)  0/44 (0.00%) 
Osteomyelitis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Pneumonia  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/8 (25.00%)  3/44 (6.82%) 
Pneumonia pneumococcal  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Pneumonia respiratory syncytial viral  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Sepsis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Upper respiratory tract infection  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Urinary tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Viral infection  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Injury, poisoning and procedural complications               
Fall  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Multiple fractures  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Subdural haematoma  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Tendon rupture  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Metabolism and nutrition disorders               
Dehydration  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Hypercalcaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Musculoskeletal and connective tissue disorders               
Bone pain  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Pathological fracture  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Breast cancer stage IV  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Nervous system disorders               
Cerebrovascular accident  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Renal and urinary disorders               
Haematuria  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Renal failure acute  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Respiratory, thoracic and mediastinal disorders               
Dyspnoea  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Epistaxis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Hypoxia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Laryngeal mass  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Pulmonary embolism  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Skin and subcutaneous tissue disorders               
Rash  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Vascular disorders               
Embolism  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Thrombosis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1: CFZ 15 mg/m² + LEN 10 mg 2: CFZ 15 mg/m² + LEN 15 mg 3: CFZ 15 mg/m² + LEN 20 mg 4: CFZ 20 mg/m² + LEN 20 mg 5: CFZ 20 mg/m² + LEN 25 mg 6: CFZ 20/27 mg/m² + LEN 25 mg 7: CFZ 20/27 mg/m² + LEN 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   6/6 (100.00%)   8/8 (100.00%)   6/6 (100.00%)   6/6 (100.00%)   8/8 (100.00%)   42/44 (95.45%) 
Blood and lymphatic system disorders               
Anaemia  1  2/6 (33.33%)  2/6 (33.33%)  6/8 (75.00%)  2/6 (33.33%)  3/6 (50.00%)  3/8 (37.50%)  14/44 (31.82%) 
Leukocytosis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Leukopenia  1  0/6 (0.00%)  3/6 (50.00%)  1/8 (12.50%)  1/6 (16.67%)  1/6 (16.67%)  2/8 (25.00%)  9/44 (20.45%) 
Lymphadenopathy  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Lymphopenia  1  1/6 (16.67%)  3/6 (50.00%)  2/8 (25.00%)  1/6 (16.67%)  0/6 (0.00%)  5/8 (62.50%)  22/44 (50.00%) 
Neutropenia  1  4/6 (66.67%)  4/6 (66.67%)  4/8 (50.00%)  2/6 (33.33%)  5/6 (83.33%)  3/8 (37.50%)  16/44 (36.36%) 
Thrombocytopenia  1  3/6 (50.00%)  3/6 (50.00%)  2/8 (25.00%)  2/6 (33.33%)  3/6 (50.00%)  3/8 (37.50%)  13/44 (29.55%) 
Cardiac disorders               
Atrial fibrillation  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Bradycardia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  0/8 (0.00%)  1/44 (2.27%) 
Extrasystoles  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Palpitations  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  2/44 (4.55%) 
Tachycardia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  4/44 (9.09%) 
Ventricular hypertrophy  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Ear and labyrinth disorders               
Cerumen impaction  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Eye disorders               
Cataract  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Conjunctivitis  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Corneal lesion  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Dry eye  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Eye haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Eye irritation  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Eye pain  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Eye swelling  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Lacrimation increased  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Ocular hyperaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Vision blurred  1  1/6 (16.67%)  1/6 (16.67%)  3/8 (37.50%)  1/6 (16.67%)  1/6 (16.67%)  1/8 (12.50%)  6/44 (13.64%) 
Gastrointestinal disorders               
Abdominal discomfort  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Abdominal distension  1  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  4/44 (9.09%) 
Abdominal pain  1  0/6 (0.00%)  2/6 (33.33%)  1/8 (12.50%)  1/6 (16.67%)  1/6 (16.67%)  1/8 (12.50%)  3/44 (6.82%) 
Abdominal pain upper  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Constipation  1  1/6 (16.67%)  2/6 (33.33%)  2/8 (25.00%)  2/6 (33.33%)  1/6 (16.67%)  3/8 (37.50%)  11/44 (25.00%) 
Diarrhoea  1  3/6 (50.00%)  3/6 (50.00%)  3/8 (37.50%)  3/6 (50.00%)  4/6 (66.67%)  4/8 (50.00%)  26/44 (59.09%) 
Dyspepsia  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Epigastric discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Faecal incontinence  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Flatulence  1  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Frequent bowel movements  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Gastrooesophageal reflux disease  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Gingival bleeding  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Gingival swelling  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Gingivitis  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Haematochezia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Mouth haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Nausea  1  1/6 (16.67%)  3/6 (50.00%)  1/8 (12.50%)  2/6 (33.33%)  1/6 (16.67%)  2/8 (25.00%)  16/44 (36.36%) 
Oesophageal discomfort  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Oral pain  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  2/44 (4.55%) 
Oral soft tissue disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Palatal disorder  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Stomach discomfort  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Stomatitis  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Toothache  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  4/44 (9.09%) 
Vomiting  1  0/6 (0.00%)  2/6 (33.33%)  2/8 (25.00%)  2/6 (33.33%)  0/6 (0.00%)  1/8 (12.50%)  11/44 (25.00%) 
General disorders               
Asthenia  1  2/6 (33.33%)  0/6 (0.00%)  3/8 (37.50%)  0/6 (0.00%)  1/6 (16.67%)  2/8 (25.00%)  5/44 (11.36%) 
Axillary pain  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Catheter site haematoma  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Catheter site haemorrhage  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Catheter site pain  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Chest discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Chest pain  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Chills  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  2/6 (33.33%)  0/6 (0.00%)  0/8 (0.00%)  5/44 (11.36%) 
Cyst  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Disease progression  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  1/44 (2.27%) 
Face oedema  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Fatigue  1  3/6 (50.00%)  4/6 (66.67%)  5/8 (62.50%)  3/6 (50.00%)  4/6 (66.67%)  6/8 (75.00%)  30/44 (68.18%) 
Feeling hot and cold  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Feeling jittery  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Feeling of body temperature change  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Gait disturbance  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Influenza like illness  1  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Infusion site bruising  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Infusion site reaction  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Injection site haemorrhage  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Injection site irritation  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Irritability  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  4/44 (9.09%) 
Malaise  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Non-cardiac chest pain  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Oedema  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Oedema peripheral  1  0/6 (0.00%)  4/6 (66.67%)  2/8 (25.00%)  0/6 (0.00%)  3/6 (50.00%)  2/8 (25.00%)  17/44 (38.64%) 
Pain  1  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  2/8 (25.00%)  4/44 (9.09%) 
Pitting oedema  1  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Pyrexia  1  0/6 (0.00%)  1/6 (16.67%)  5/8 (62.50%)  3/6 (50.00%)  1/6 (16.67%)  4/8 (50.00%)  19/44 (43.18%) 
Temperature intolerance  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Vessel puncture site haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Hepatobiliary disorders               
Hyperbilirubinaemia  1  0/6 (0.00%)  0/6 (0.00%)  3/8 (37.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Immune system disorders               
Drug hypersensitivity  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Seasonal allergy  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Infections and infestations               
Bronchitis  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Candidiasis  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Catheter site cellulitis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Cellulitis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  3/44 (6.82%) 
Eye infection  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Folliculitis  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Fungal infection  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Gastroenteritis viral  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Herpes simplex  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Influenza  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Lobar pneumonia  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Nasopharyngitis  1  1/6 (16.67%)  2/6 (33.33%)  1/8 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  8/44 (18.18%) 
Oral candidiasis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Pneumonia  1  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  4/44 (9.09%) 
Rhinitis  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Sinusitis  1  0/6 (0.00%)  0/6 (0.00%)  4/8 (50.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  4/44 (9.09%) 
Upper respiratory tract infection  1  2/6 (33.33%)  3/6 (50.00%)  4/8 (50.00%)  1/6 (16.67%)  0/6 (0.00%)  4/8 (50.00%)  19/44 (43.18%) 
Urinary tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  3/44 (6.82%) 
Viral infection  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Injury, poisoning and procedural complications               
Contusion  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  2/6 (33.33%)  0/8 (0.00%)  5/44 (11.36%) 
Fall  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Humerus fracture  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Incision site complication  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Scratch  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Skin laceration  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Transfusion reaction  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Investigations               
Alanine aminotransferase increased  1  1/6 (16.67%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  7/44 (15.91%) 
Aspartate aminotransferase increased  1  1/6 (16.67%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  6/44 (13.64%) 
Blood alkaline phosphatase increased  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Blood bicarbonate decreased  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  3/44 (6.82%) 
Blood bilirubin increased  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Blood calcium decreased  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Blood creatinine increased  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/8 (25.00%)  4/44 (9.09%) 
Blood magnesium decreased  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Cardiac murmur  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Ejection fraction decreased  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Haemoglobin decreased  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  3/44 (6.82%) 
Heart rate irregular  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
International normalised ratio increased  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Platelet count decreased  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Weight decreased  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  2/6 (33.33%)  0/8 (0.00%)  3/44 (6.82%) 
Weight increased  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Metabolism and nutrition disorders               
Anorexia  1  0/6 (0.00%)  2/6 (33.33%)  1/8 (12.50%)  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  7/44 (15.91%) 
Decreased appetite  1  1/6 (16.67%)  3/6 (50.00%)  1/8 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  4/44 (9.09%) 
Dehydration  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  5/44 (11.36%) 
Hypercalcaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Hyperglycaemia  1  1/6 (16.67%)  2/6 (33.33%)  1/8 (12.50%)  3/6 (50.00%)  2/6 (33.33%)  3/8 (37.50%)  11/44 (25.00%) 
Hyperkalaemia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Hypermagnesaemia  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  2/8 (25.00%)  2/44 (4.55%) 
Hyperphosphataemia  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Hyperphosphatasaemia  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Hyperuricaemia  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Hypoalbuminaemia  1  1/6 (16.67%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  3/44 (6.82%) 
Hypocalcaemia  1  0/6 (0.00%)  2/6 (33.33%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  5/44 (11.36%) 
Hypoglycaemia  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  3/44 (6.82%) 
Hypokalaemia  1  0/6 (0.00%)  3/6 (50.00%)  3/8 (37.50%)  2/6 (33.33%)  1/6 (16.67%)  1/8 (12.50%)  12/44 (27.27%) 
Hypomagnesaemia  1  0/6 (0.00%)  2/6 (33.33%)  1/8 (12.50%)  2/6 (33.33%)  1/6 (16.67%)  2/8 (25.00%)  9/44 (20.45%) 
Hyponatraemia  1  0/6 (0.00%)  2/6 (33.33%)  2/8 (25.00%)  1/6 (16.67%)  1/6 (16.67%)  3/8 (37.50%)  5/44 (11.36%) 
Hypophosphataemia  1  0/6 (0.00%)  1/6 (16.67%)  3/8 (37.50%)  0/6 (0.00%)  1/6 (16.67%)  4/8 (50.00%)  16/44 (36.36%) 
Iron deficiency  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Lactose intolerance  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  2/6 (33.33%)  2/6 (33.33%)  3/8 (37.50%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  12/44 (27.27%) 
Back pain  1  2/6 (33.33%)  3/6 (50.00%)  3/8 (37.50%)  1/6 (16.67%)  2/6 (33.33%)  1/8 (12.50%)  15/44 (34.09%) 
Bone pain  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Chest wall pain  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  2/6 (33.33%)  1/6 (16.67%)  0/8 (0.00%)  6/44 (13.64%) 
Groin pain  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Joint range of motion decreased  1  0/6 (0.00%)  1/6 (16.67%)  2/8 (25.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Joint swelling  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Muscle spasms  1  1/6 (16.67%)  4/6 (66.67%)  4/8 (50.00%)  1/6 (16.67%)  1/6 (16.67%)  3/8 (37.50%)  17/44 (38.64%) 
Muscle twitching  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Muscular weakness  1  1/6 (16.67%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  2/44 (4.55%) 
Musculoskeletal discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Musculoskeletal stiffness  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Myalgia  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  2/6 (33.33%)  0/8 (0.00%)  5/44 (11.36%) 
Neck pain  1  0/6 (0.00%)  1/6 (16.67%)  2/8 (25.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Pain in extremity  1  1/6 (16.67%)  1/6 (16.67%)  4/8 (50.00%)  1/6 (16.67%)  1/6 (16.67%)  2/8 (25.00%)  11/44 (25.00%) 
Pain in jaw  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  5/44 (11.36%) 
Pathological fracture  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  4/44 (9.09%) 
Sacral pain  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Shoulder pain  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  3/6 (50.00%)  1/6 (16.67%)  2/8 (25.00%)  3/44 (6.82%) 
Tendonitis  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Benign neoplasm of skin  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Lung neoplasm  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  1/44 (2.27%) 
Malignant melanoma  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Plasmacytoma  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Nervous system disorders               
Aphasia  1  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Areflexia  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Balance disorder  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Convulsion  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Dizziness  1  0/6 (0.00%)  2/6 (33.33%)  2/8 (25.00%)  1/6 (16.67%)  2/6 (33.33%)  1/8 (12.50%)  6/44 (13.64%) 
Dysgeusia  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  5/44 (11.36%) 
Dysstasia  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Headache  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  3/6 (50.00%)  2/6 (33.33%)  0/8 (0.00%)  11/44 (25.00%) 
Hyperaesthesia  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Hypoaesthesia  1  1/6 (16.67%)  2/6 (33.33%)  2/8 (25.00%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  8/44 (18.18%) 
Hyporeflexia  1  2/6 (33.33%)  2/6 (33.33%)  1/8 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Memory impairment  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  1/44 (2.27%) 
Nerve compression  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Neuropathic pain  1  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  0/6 (0.00%)  2/8 (25.00%)  5/44 (11.36%) 
Neuropathy peripheral  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/6 (33.33%)  0/6 (0.00%)  0/8 (0.00%)  12/44 (27.27%) 
Paraesthesia  1  2/6 (33.33%)  3/6 (50.00%)  2/8 (25.00%)  0/6 (0.00%)  0/6 (0.00%)  3/8 (37.50%)  9/44 (20.45%) 
Peripheral sensory neuropathy  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Sciatica  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Somnolence  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  4/44 (9.09%) 
Tremor  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  4/44 (9.09%) 
Psychiatric disorders               
Affect lability  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Agitation  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  3/44 (6.82%) 
Anxiety  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  1/8 (12.50%)  7/44 (15.91%) 
Anxiety disorder  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Confusional state  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  2/44 (4.55%) 
Depression  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  4/44 (9.09%) 
Insomnia  1  1/6 (16.67%)  3/6 (50.00%)  3/8 (37.50%)  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  17/44 (38.64%) 
Mood altered  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Mood swings  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Stress  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Renal and urinary disorders               
Dysuria  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Haematuria  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Incontinence  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Micturition urgency  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Nocturia  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  2/44 (4.55%) 
Proteinuria  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Renal failure  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Urinary hesitation  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Urinary retention  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Reproductive system and breast disorders               
Atrophic vulvovaginitis  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Pelvic pain  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Postmenopausal haemorrhage  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Vaginal haemorrhage  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  1/6 (16.67%)  5/6 (83.33%)  3/8 (37.50%)  2/6 (33.33%)  3/6 (50.00%)  4/8 (50.00%)  17/44 (38.64%) 
Dry throat  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Dysphonia  1  2/6 (33.33%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  6/44 (13.64%) 
Dyspnoea  1  0/6 (0.00%)  3/6 (50.00%)  3/8 (37.50%)  2/6 (33.33%)  3/6 (50.00%)  3/8 (37.50%)  15/44 (34.09%) 
Dyspnoea exertional  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  5/44 (11.36%) 
Epistaxis  1  1/6 (16.67%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  6/44 (13.64%) 
Haemoptysis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Hiccups  1  2/6 (33.33%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Lung infiltration  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Nasal congestion  1  0/6 (0.00%)  0/6 (0.00%)  2/8 (25.00%)  1/6 (16.67%)  0/6 (0.00%)  1/8 (12.50%)  7/44 (15.91%) 
Pharyngeal erythema  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Pharyngolaryngeal pain  1  0/6 (0.00%)  0/6 (0.00%)  3/8 (37.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  12/44 (27.27%) 
Pleural effusion  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  1/44 (2.27%) 
Pleuritic pain  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Productive cough  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  7/44 (15.91%) 
Pulmonary oedema  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Rales  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Respiratory tract congestion  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Rhinorrhoea  1  0/6 (0.00%)  2/6 (33.33%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  6/44 (13.64%) 
Sinus congestion  1  0/6 (0.00%)  0/6 (0.00%)  3/8 (37.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Sleep apnoea syndrome  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  1/44 (2.27%) 
Throat irritation  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Throat tightness  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Wheezing  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  3/44 (6.82%) 
Skin and subcutaneous tissue disorders               
Dermatitis contact  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Dry skin  1  1/6 (16.67%)  2/6 (33.33%)  1/8 (12.50%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  11/44 (25.00%) 
Ecchymosis  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  4/44 (9.09%) 
Erythema  1  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Hair growth abnormal  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Hyperhidrosis  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  4/44 (9.09%) 
Increased tendency to bruise  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Nail discolouration  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Nail disorder  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Night sweats  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  5/44 (11.36%) 
Petechiae  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Pruritus  1  0/6 (0.00%)  2/6 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/8 (12.50%)  4/44 (9.09%) 
Rash  1  0/6 (0.00%)  2/6 (33.33%)  4/8 (50.00%)  1/6 (16.67%)  2/6 (33.33%)  2/8 (25.00%)  8/44 (18.18%) 
Rash generalised  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  2/44 (4.55%) 
Rash macular  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  3/44 (6.82%) 
Rash pruritic  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Skin discolouration  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Skin disorder  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Skin exfoliation  1  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Skin fragility  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Skin haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  1/44 (2.27%) 
Skin lesion  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/44 (2.27%) 
Subcutaneous nodule  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Swelling face  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Surgical and medical procedures               
Tooth extraction  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Vascular disorders               
Deep vein thrombosis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  5/44 (11.36%) 
Flushing  1  1/6 (16.67%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Haematoma  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/44 (0.00%) 
Hypertension  1  0/6 (0.00%)  2/6 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  4/44 (9.09%) 
Peripheral coldness  1  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Phlebitis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  1/44 (2.27%) 
Post thrombotic syndrome  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Thrombophlebitis superficial  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/8 (0.00%)  2/44 (4.55%) 
Vascular fragility  1  0/6 (0.00%)  0/6 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/44 (0.00%) 
Vena cava thrombosis  1  0/6 (0.00%)  0/6 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/8 (0.00%)  0/44 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen, Inc.
Phone: 866-572-6436
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00603447     History of Changes
Other Study ID Numbers: PX-171-006
First Submitted: January 16, 2008
First Posted: January 29, 2008
Results First Submitted: May 15, 2015
Results First Posted: June 3, 2015
Last Update Posted: May 30, 2017