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Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies

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ClinicalTrials.gov Identifier: NCT00150462
Recruitment Status : Completed
First Posted : September 8, 2005
Results First Posted : December 3, 2015
Last Update Posted : May 2, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Waldenstrom's Macroglobulinemia
Non-Hodgkin's Lymphoma
Hodgkin's Disease
Multiple Myeloma
Interventions Drug: Carfilzomib
Drug: Dexamethasone
Enrollment 48
Recruitment Details Adults with with multiple myeloma (MM)—both secretory and nonsecretory, non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease (HD), or Waldenström’s macroglobulinemia (WM) were eligible for enrollment in this study.
Pre-assignment Details The study was divided into a sequential Dose Escalation phase (Part 1; Arms 1-9), followed by a Dose Expansion phase (Part 2; Arms 10-11) consisting of a carfilzomib-only cohort and a carfilzomib-plus dexamethasone cohort.
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Hide Arm/Group Description Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Period Title: Overall Study
Started 3 3 4 3 3 4 3 8 6 7 4
Completed 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 1 [2] 1 [2]
Not Completed 3 3 4 3 3 4 3 8 6 6 3
Reason Not Completed
Disease Progression or Relapse             3             1             2             1             2             2             3             5             5             3             2
Withdrawal by Subject             0             1             1             0             1             2             0             1             0             1             0
Death             0             1             0             0             0             0             0             0             1             0             0
Adverse Event             0             0             0             1             0             0             0             2             0             1             0
Physician Decision             0             0             1             1             0             0             0             0             0             0             0
Other             0             0             0             0             0             0             0             0             0             1             1
[1]
Indicates participants remaining on study treatment
[2]
Indicates participants who completed 12 cycles of treatment.
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX Total
Hide Arm/Group Description Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly). Total of all reporting groups
Overall Number of Baseline Participants 3 3 4 3 3 4 3 8 6 7 4 48
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 4 participants 3 participants 3 participants 4 participants 3 participants 8 participants 6 participants 7 participants 4 participants 48 participants
Dose Escalation (Part 1) 62.5  (17.47) 69.6  (4.80) 55.3  (21.71) 51.7  (6.20) 61.6  (9.15) 61.3  (3.76) 50.3  (12.99) 60.6  (11.99) 67.6  (9.82) NA [1]   (NA) NA [1]   (NA) 60.6  (12.25)
Dose Expansion (Part 2) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 66.3  (9.21) 54.3  (13.57) 61.9  (11.96)
[1]
Not applicable for Part 2 groups
[2]
Not applicable for Part 1 groups
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 4 participants 3 participants 3 participants 4 participants 3 participants 8 participants 6 participants 7 participants 4 participants 48 participants
Female
0
   0.0%
2
  66.7%
3
  75.0%
2
  66.7%
1
  33.3%
4
 100.0%
1
  33.3%
2
  25.0%
2
  33.3%
2
  28.6%
3
  75.0%
22
  45.8%
Male
3
 100.0%
1
  33.3%
1
  25.0%
1
  33.3%
2
  66.7%
0
   0.0%
2
  66.7%
6
  75.0%
4
  66.7%
5
  71.4%
1
  25.0%
26
  54.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 4 participants 3 participants 3 participants 4 participants 3 participants 8 participants 6 participants 7 participants 4 participants 48 participants
African American 0 0 0 0 1 0 0 0 0 1 1 3
Caucasian 3 2 3 3 2 4 3 7 6 6 3 42
Hispanic 0 1 0 0 0 0 0 0 0 0 0 1
Native American 0 0 1 0 0 0 0 1 0 0 0 2
Disease Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 4 participants 3 participants 3 participants 4 participants 3 participants 8 participants 6 participants 7 participants 4 participants 48 participants
Multiple Myeloma 0 3 0 2 1 2 2 6 5 3 4 28
Non-Hodgkin's Lymphoma 3 0 3 1 2 2 1 2 1 2 0 17
Waldenstrom's Macroglobulinemia 0 0 0 0 0 0 0 0 0 2 0 2
Hodgkin's Disease 0 0 1 0 0 0 0 0 0 0 0 1
1.Primary Outcome
Title Number of Participants With Dose-limiting Toxicities (DLTs)
Hide Description

A DLT was defined as any of the following occurring in the first 28 days of study participation:

Nonhematologic:

  • > Grade 2 neuropathy with pain
  • ≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, or diarrhea)
  • ≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy

Hematologic:

  • Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10ˆ9/L) lasting ≥ 14 days without hematopoietic growth factor support
  • Febrile neutropenia (ANC < 1.0 × 10ˆ9/L with a fever ≥ 38.3°C)
  • Grade 4 thrombocytopenia (platelets < 25.0 × 10ˆ9/L) or thrombocytopenia associated with bleeding.

Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 3.0.

Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety-evaluable: All participants who were enrolled and received at least 1 dose of carfilzomib
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Overall Number of Participants Analyzed 3 3 4 3 3 4 3 8 6 7 4
Measure Type: Number
Unit of Measure: participants
1 0 0 0 0 0 0 1 1 0 1
2.Primary Outcome
Title Maximum Observed Plasma Concentration of Carfilzomib (Cmax)
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with available pharmacokinetic (PK) data. Cmax was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2-8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² (±DEX)
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants in the Dose Expansion phase received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Overall Number of Participants Analyzed 0 0 0 0 0 3 3 8 5 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
505.17  (485.12) 142.67  (97.22) 527.50  (405.59) 406.08  (517.29) 390.66  (492.92)
3.Primary Outcome
Title Time to Maximum Observed Plasma Concentration of Carfilzomib (Tmax)
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with available pharmacokinetic (PK) data. Tmax was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2-8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² (±DEX)
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants in the Dose Expansion phase received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Overall Number of Participants Analyzed 0 0 0 0 0 3 3 8 5 8
Mean (Standard Deviation)
Unit of Measure: minutes
5  (0) 6  (1) 7  (2) 6  (2) 16  (11)
4.Primary Outcome
Title Area Under the Concentration-time Curve to Last Measureable Timepoint (AUClast) for Carfilzomib
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with available pharmacokinetic (PK) data. AUClast was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2–8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² (±DEX)
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants in the Dose Expansion phase received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Overall Number of Participants Analyzed 0 0 0 0 0 3 3 8 5 8
Mean (Standard Deviation)
Unit of Measure: ng*minute/mL
4049  (3695) 1414  (919) 4911  (3495) 3409  (3964) 4970  (5817)
5.Primary Outcome
Title Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) for Carfilzomib
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with available pharmacokinetic (PK) data. AUCinf was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2–8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² (±DEX)
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants in the Dose Expansion phase received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Overall Number of Participants Analyzed 0 0 0 0 0 3 3 8 5 8
Mean (Standard Deviation)
Unit of Measure: ng*minute/mL
4056  (3698) 1420  (922) 4942  (3497) 3417  (3962) 4997  (5812)
6.Secondary Outcome
Title Best Clinical Response to Treatment
Hide Description

Disease response criteria for NHL were according to the International Working Group Criteria for Non-Hodgkin’s Lymphoma. Disease response criteria for Multiple Myeloma were according to the European Group for Blood and Marrow Transplantation (EBMT). Disease response criteria for WM were according to the consensus panel recommendations from the Second International Workshop on Waldenström’s Macroglobulinemia. The disease response criteria for Hodgkin’s Lymphoma are defined as follows:

  • Complete response: total resolution of measurable disease parameters.
  • Partial response: a ≥ 50% resolution without the appearance of new disease.
  • Stable disease: between < 50% resolution and ≤ 25% increases in measurable disease parameters without appearance of new disease.
  • Progressive disease: an increase of > 25% in measurable disease parameters.

Best clinical response is the best response observed from the start of study treatment until disease progression or death.

Time Frame From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
Hide Outcome Measure Data
Hide Analysis Population Description
Biologic response-evaluable: All participants who received at least 1 cycle of carfilzomib and had both baseline and at least 1 post-baseline disease assessment.
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Overall Number of Participants Analyzed 1 2 3 2 3 3 2 6 5 6 3
Measure Type: Number
Unit of Measure: participants
Complete Response 0 0 0 0 0 0 0 0 0 0 0
Partial Response 0 0 0 0 0 0 1 1 2 2 0
Minimal Response 0 0 0 0 0 0 0 0 1 0 1
Stable Disease/No Change 0 1 1 2 1 1 0 2 1 2 0
Progressive Disease 1 1 1 0 2 2 1 3 1 2 2
Unknown 0 0 1 0 0 0 0 0 0 0 0
7.Secondary Outcome
Title Duration of Response
Hide Description

Duration of objective response is defined as the time from the date of first documented assessment of clinical response (confirmed or unconfirmed complete response, partial response, or minimal response) to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment.

Median duration of response was calculated using the Kaplan-Meier method.

Time Frame From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
Hide Outcome Measure Data
Hide Analysis Population Description
Biologic response-evaluable participants with an objective response
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15, and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15, and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Overall Number of Participants Analyzed 0 0 0 0 0 0 1 1 3 2 1
Median (Full Range)
Unit of Measure: days
308.0
(308.0 to 308.0)
176.0
(176.0 to 176.0)
225.0
(94.0 to 316.0)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Could not be calculated due to the low number of events
8.Secondary Outcome
Title Time to Progression
Hide Description

Time to progressive disease is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease, plus one day. Participants without tumor progression were censored at the date of their last clinical response assessment.

Median time to progression was calculated using the Kaplan-Meier method.

Time Frame From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
Hide Outcome Measure Data
Hide Analysis Population Description
Biologic response-evaluable population
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Overall Number of Participants Analyzed 1 2 3 2 3 3 2 6 5 6 3
Median (Full Range)
Unit of Measure: days
114.0
(114.0 to 114.0)
232.0
(57.0 to 407.0)
NA [1] 
(54.0 to 54.0)
NA [1] 
(NA to NA)
55.0
(47.0 to 55.0)
48.0
(15.0 to 176.0)
186.0
(50.0 to 322.0)
110.5
(15.0 to 190.0)
225.0
(36.0 to 330.0)
NA [1] 
(15.0 to 99.0)
49.0
(23.0 to 49.0)
[1]
Not estimable due to the low number of events
9.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment. Median progression-free survival was calculated using the Kaplan-Meier method.
Time Frame From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
Hide Outcome Measure Data
Hide Analysis Population Description
Biologic response-evaluable population
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Hide Arm/Group Description:
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Overall Number of Participants Analyzed 1 2 3 2 3 3 2 6 5 6 3
Median (Full Range)
Unit of Measure: days
114.0
(114.0 to 114.0)
232.0
(57.0 to 407.0)
NA [1] 
(54.0 to 54.0)
NA [1] 
(NA to NA)
55.0
(47.0 to 55.0)
48.0
(15.0 to 176.0)
186.0
(50.0 to 322.0)
110.5
(15.0 to 190.0)
225.0
(36.0 to 330.0)
NA [1] 
(15.0 to 99.0)
49.0
(23.0 to 49.0)
[1]
Could not be estimated due to the low number of events
Time Frame From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Hide Arm/Group Description Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles. Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
All-Cause Mortality
CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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
CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/3 (66.67%)   1/3 (33.33%)   3/4 (75.00%)   2/3 (66.67%)   2/3 (66.67%)   2/4 (50.00%)   1/3 (33.33%)   3/8 (37.50%)   4/6 (66.67%)   3/7 (42.86%)   2/4 (50.00%) 
Blood and lymphatic system disorders                       
Anaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Febrile neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Hyperviscosity syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Thrombocytopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders                       
Abdominal distension  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Abdominal pain upper  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pancreatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
General disorders                       
Multi-organ failure  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Non-cardiac chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Pyrexia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Infections and infestations                       
Bronchitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pneumonia  1  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Sepsis  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Septic shock  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Sinusitis  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Injury, poisoning and procedural complications                       
Rib fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Investigations                       
Aspartate aminotransferase increased  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Glomerular filtration rate decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders                       
Dehydration  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Hypocalcaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hyponatraemia  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders                       
Pain in extremity  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Pathological fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                       
Tumour associated fever  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Nervous system disorders                       
Speech disorder  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Spinal cord compression  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Syncope  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Unresponsive to verbal stimuli  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Psychiatric disorders                       
Mental status changes  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders                       
Renal failure  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Renal failure acute  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders                       
Dyspnoea exacerbated  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Hypoxia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/4 (25.00%) 
Pleural effusion  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Vascular disorders                       
Hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/4 (25.00%) 
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%
CFZ 1.2 mg/m² CFZ 2.4 mg/m² CFZ 4.0 mg/m² CFZ 6.0 mg/m² CFZ 8.4 mg/m² CFZ 11.0 mg/m² CFZ 15.0 mg/m² CFZ 20.0 mg/m² CFZ 27.0 mg/m² CFZ 20/27 mg/m² CFZ 20/27 mg/m² + DEX
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   3/3 (100.00%)   4/4 (100.00%)   3/3 (100.00%)   3/3 (100.00%)   4/4 (100.00%)   3/3 (100.00%)   8/8 (100.00%)   6/6 (100.00%)   7/7 (100.00%)   4/4 (100.00%) 
Blood and lymphatic system disorders                       
Anaemia  1  1/3 (33.33%)  3/3 (100.00%)  0/4 (0.00%)  2/3 (66.67%)  0/3 (0.00%)  1/4 (25.00%)  2/3 (66.67%)  4/8 (50.00%)  4/6 (66.67%)  4/7 (57.14%)  4/4 (100.00%) 
Febrile neutropenia  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Leukopenia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  1/4 (25.00%) 
Lymph node pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Lymphopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Neutropenia  1  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  1/7 (14.29%)  2/4 (50.00%) 
Pancytopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Thrombocytopenia  1  0/3 (0.00%)  1/3 (33.33%)  3/4 (75.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  3/8 (37.50%)  3/6 (50.00%)  4/7 (57.14%)  3/4 (75.00%) 
Cardiac disorders                       
Bradycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Cardiac flutter  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Cardiomegaly  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Sinus tachycardia  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  1/4 (25.00%) 
Ear and labyrinth disorders                       
Deafness  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Ear pain  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Tinnitus  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Vertigo  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Eye disorders                       
Cataract  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Conjunctival hyperaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Dry eye  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  0/4 (0.00%) 
Exophthalmos  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Eye pain  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Eyelid irritation  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Eyelid oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Ocular hyperaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Vision blurred  1  2/3 (66.67%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders                       
Abdominal distension  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Abdominal pain  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Abdominal pain upper  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Cheilitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Constipation  1  2/3 (66.67%)  0/3 (0.00%)  2/4 (50.00%)  1/3 (33.33%)  2/3 (66.67%)  2/4 (50.00%)  0/3 (0.00%)  4/8 (50.00%)  3/6 (50.00%)  2/7 (28.57%)  0/4 (0.00%) 
Diarrhoea  1  0/3 (0.00%)  1/3 (33.33%)  2/4 (50.00%)  2/3 (66.67%)  1/3 (33.33%)  2/4 (50.00%)  0/3 (0.00%)  2/8 (25.00%)  2/6 (33.33%)  3/7 (42.86%)  2/4 (50.00%) 
Dry mouth  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Dyspepsia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Dysphagia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Epigastric discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Faeces discoloured  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Gingival bleeding  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Gingival pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Gingivitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Glossodynia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Inguinal hernia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Nausea  1  2/3 (66.67%)  0/3 (0.00%)  3/4 (75.00%)  1/3 (33.33%)  2/3 (66.67%)  2/4 (50.00%)  3/3 (100.00%)  5/8 (62.50%)  4/6 (66.67%)  3/7 (42.86%)  0/4 (0.00%) 
Oedema mouth  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Oesophageal pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Small intestinal obstruction  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Stomatitis  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  0/4 (0.00%) 
Vomiting  1  0/3 (0.00%)  0/3 (0.00%)  3/4 (75.00%)  2/3 (66.67%)  1/3 (33.33%)  3/4 (75.00%)  1/3 (33.33%)  2/8 (25.00%)  1/6 (16.67%)  1/7 (14.29%)  0/4 (0.00%) 
General disorders                       
Adverse drug reaction  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Asthenia  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Catheter site haematoma  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Catheter site pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Chest discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Chills  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  3/8 (37.50%)  2/6 (33.33%)  2/7 (28.57%)  0/4 (0.00%) 
Face oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Fatigue  1  2/3 (66.67%)  0/3 (0.00%)  3/4 (75.00%)  1/3 (33.33%)  1/3 (33.33%)  3/4 (75.00%)  3/3 (100.00%)  3/8 (37.50%)  3/6 (50.00%)  4/7 (57.14%)  1/4 (25.00%) 
Generalised oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Infusion related reaction  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Infusion site erythema  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Infusion site pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  0/4 (0.00%) 
Injection site haemorrhage  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Malaise  1  2/3 (66.67%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Mucosal inflammation  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Non-cardiac chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/4 (25.00%) 
Oedema  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Oedema peripheral  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%)  1/3 (33.33%)  1/8 (12.50%)  2/6 (33.33%)  3/7 (42.86%)  0/4 (0.00%) 
Pain  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  1/8 (12.50%)  1/6 (16.67%)  1/7 (14.29%)  0/4 (0.00%) 
Pitting oedema  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pyrexia  1  1/3 (33.33%)  1/3 (33.33%)  3/4 (75.00%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  2/3 (66.67%)  2/8 (25.00%)  3/6 (50.00%)  3/7 (42.86%)  0/4 (0.00%) 
Immune system disorders                       
Drug hypersensitivity  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Infections and infestations                       
Bronchiolitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Bronchitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Candidiasis  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Ear infection  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Echinococciasis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Folliculitis  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Fungal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Furuncle  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Herpes simplex  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Herpes zoster  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Infection  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Lung infection  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Nasopharyngitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Oral candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Pneumonia primary atypical  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Sinusitis  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Staphylococcal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Upper respiratory tract infection  1  0/3 (0.00%)  2/3 (66.67%)  1/4 (25.00%)  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  1/8 (12.50%)  2/6 (33.33%)  1/7 (14.29%)  1/4 (25.00%) 
Urinary tract infection  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  2/4 (50.00%) 
Injury, poisoning and procedural complications                       
Contusion  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Fall  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  0/4 (0.00%) 
Investigations                       
Alanine aminotransferase increased  1  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/4 (25.00%) 
Aspartate aminotransferase increased  1  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Atrial natriuretic peptide increased  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Blood amylase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Blood bilirubin increased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Blood creatinine increased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  1/8 (12.50%)  3/6 (50.00%)  2/7 (28.57%)  1/4 (25.00%) 
Blood lactate dehydrogenase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Blood magnesium decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Blood phosphorus decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Blood phosphorus increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Blood potassium decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Blood pressure increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Blood sodium decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Blood urea increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Body temperature increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Electrocardiogram QT corrected interval prolonged  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Gamma-glutamyltransferase increased  1  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Haematocrit decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Haemoglobin decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Lipase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Lymphocyte count increased  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Neutrophil count decreased  1  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Oxygen saturation decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Platelet count decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Red blood cell count decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Transaminases increased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Troponin I increased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Urine output decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Weight decreased  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Weight increased  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
White blood cell count decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders                       
Anorexia  1  2/3 (66.67%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  3/8 (37.50%)  3/6 (50.00%)  1/7 (14.29%)  0/4 (0.00%) 
Decreased appetite  1  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  1/4 (25.00%) 
Dehydration  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  1/8 (12.50%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Fluid overload  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Fluid retention  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hypercalcaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  0/4 (0.00%) 
Hypercholesterolaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hyperglycaemia  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  0/4 (0.00%)  0/3 (0.00%)  4/8 (50.00%)  1/6 (16.67%)  2/7 (28.57%)  0/4 (0.00%) 
Hyperkalaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  2/7 (28.57%)  1/4 (25.00%) 
Hypermagnesaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  2/4 (50.00%) 
Hypernatraemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Hyperphosphataemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hyperuricaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hypoalbuminaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  2/7 (28.57%)  1/4 (25.00%) 
Hypocalcaemia  1  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  1/4 (25.00%) 
Hypoglycaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Hypokalaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Hypomagnesaemia  1  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  1/6 (16.67%)  1/7 (14.29%)  1/4 (25.00%) 
Hyponatraemia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  2/7 (28.57%)  0/4 (0.00%) 
Hypophosphataemia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  1/4 (25.00%) 
Musculoskeletal and connective tissue disorders                       
Arthralgia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  5/6 (83.33%)  0/7 (0.00%)  1/4 (25.00%) 
Back pain  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  2/6 (33.33%)  0/7 (0.00%)  0/4 (0.00%) 
Bone pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  1/8 (12.50%)  1/6 (16.67%)  0/7 (0.00%)  1/4 (25.00%) 
Chest wall pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Flank pain  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Groin pain  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Muscle spasms  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Musculoskeletal discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Myalgia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Osteolysis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Pain in extremity  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Pain in jaw  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Shoulder pain  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  2/4 (50.00%)  1/3 (33.33%)  0/8 (0.00%)  3/6 (50.00%)  0/7 (0.00%)  0/4 (0.00%) 
Tendonitis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                       
Lipoma  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Skin cancer  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Nervous system disorders                       
Asterixis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Dizziness  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Encephalopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Headache  1  1/3 (33.33%)  0/3 (0.00%)  2/4 (50.00%)  1/3 (33.33%)  2/3 (66.67%)  1/4 (25.00%)  0/3 (0.00%)  2/8 (25.00%)  2/6 (33.33%)  1/7 (14.29%)  1/4 (25.00%) 
Hypoaesthesia  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Lethargy  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Memory impairment  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Neuropathy  1  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Neuropathy peripheral  1  0/3 (0.00%)  0/3 (0.00%)  2/4 (50.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Paraesthesia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Sinus headache  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Somnolence  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Psychiatric disorders                       
Anxiety  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  2/8 (25.00%)  3/6 (50.00%)  0/7 (0.00%)  0/4 (0.00%) 
Confusional state  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Depression  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Insomnia  1  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  3/6 (50.00%)  3/7 (42.86%)  1/4 (25.00%) 
Paranoia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders                       
Bladder disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Bladder spasm  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Dysuria  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  3/8 (37.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Renal failure  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Renal failure acute  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders                       
Bronchospasm  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Cough  1  0/3 (0.00%)  1/3 (33.33%)  2/4 (50.00%)  1/3 (33.33%)  3/3 (100.00%)  2/4 (50.00%)  1/3 (33.33%)  0/8 (0.00%)  4/6 (66.67%)  3/7 (42.86%)  1/4 (25.00%) 
Crackles lung  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Dry throat  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Dysphonia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Dyspnoea  1  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%)  2/3 (66.67%)  4/8 (50.00%)  2/6 (33.33%)  1/7 (14.29%)  1/4 (25.00%) 
Dyspnoea exertional  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  2/8 (25.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Epistaxis  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Hiccups  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hypoxia  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Nasal congestion  1  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  2/3 (66.67%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Pharyngolaryngeal pain  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  2/3 (66.67%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  1/4 (25.00%) 
Pleural effusion  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Postnasal drip  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Productive cough  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  2/8 (25.00%)  0/6 (0.00%)  0/7 (0.00%)  1/4 (25.00%) 
Pulmonary congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pulmonary hypertension  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pulmonary oedema  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Respiratory tract congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Rhinorrhoea  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Rhonchi  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Sinus congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Upper respiratory tract congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Wheezing  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Skin and subcutaneous tissue disorders                       
Alopecia  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  0/4 (0.00%) 
Cold sweat  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Decubitus ulcer  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Dry skin  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Ecchymosis  1  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hyperhidrosis  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Hypotrichosis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Increased tendency to bruise  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  0/4 (0.00%) 
Night sweats  1  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pain of skin  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Pruritus  1  1/3 (33.33%)  0/3 (0.00%)  2/4 (50.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Rash  1  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Rash generalised  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Rash pruritic  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/4 (0.00%) 
Skin discolouration  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Surgical and medical procedures                       
Nasal sinus drainage  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Vascular disorders                       
Aneurysm  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Deep vein thrombosis  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Haematoma  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/8 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (0.00%) 
Hypertension  1  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/8 (12.50%)  3/6 (50.00%)  0/7 (0.00%)  0/4 (0.00%) 
Hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/4 (0.00%) 
Orthostatic hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/7 (0.00%)  0/4 (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
Name/Title: Study Director
Organization: Amgen, Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00150462     History of Changes
Other Study ID Numbers: PX-171-002
First Submitted: September 6, 2005
First Posted: September 8, 2005
Results First Submitted: October 29, 2015
Results First Posted: December 3, 2015
Last Update Posted: May 2, 2017