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A Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma (CHAMPION 1)

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ClinicalTrials.gov Identifier: NCT01677858
Recruitment Status : Completed
First Posted : September 3, 2012
Results First Posted : August 9, 2017
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Carfilzomib
Drug: Dexamethasone
Enrollment 116
Recruitment Details This study was conducted at 32 centers in the United States. Participants were enrolled from September 2012 to September 2014.
Pre-assignment Details In phase 1 participants were enrolled into 1 of 4 sequential dose-escalating cohorts to establish the maximum tolerated dose (MTD) of carfilzomib plus dexamethasone. In phase 2 participants were enrolled to evaluate the efficacy and safety of carfilzomib plus dexamethasone at the MTD established in phase 1.
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m²
Hide Arm/Group Description Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Period Title: Overall Study
Started 3 3 15 6 89
Completed 0 [1] 1 [1] 1 [1] 0 [1] 4 [1]
Not Completed 3 2 14 6 85
Reason Not Completed
Adverse Event             0             0             2             3             13
Death             0             0             0             0             1
Physician Decision             1             0             2             0             12
Progressive Disease             2             1             9             3             43
Withdrawal by Subject             0             1             1             0             15
Lost to Follow-up             0             0             0             0             1
[1]
Completed indicates participants ongoing in study
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m² Total
Hide Arm/Group Description Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Total of all reporting groups
Overall Number of Baseline Participants 3 3 15 6 89 116
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 15 participants 6 participants 89 participants 116 participants
69.3  (15.6) 73.7  (2.1) 62.4  (10.4) 58.2  (8.8) 68.7  (9.6) 67.5  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 15 participants 6 participants 89 participants 116 participants
Female
1
  33.3%
2
  66.7%
4
  26.7%
5
  83.3%
40
  44.9%
52
  44.8%
Male
2
  66.7%
1
  33.3%
11
  73.3%
1
  16.7%
49
  55.1%
64
  55.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 15 participants 6 participants 89 participants 116 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
10
  11.2%
11
   9.5%
Not Hispanic or Latino
3
 100.0%
3
 100.0%
15
 100.0%
5
  83.3%
79
  88.8%
105
  90.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 15 participants 6 participants 89 participants 116 participants
White
3
 100.0%
2
  66.7%
11
  73.3%
6
 100.0%
79
  88.8%
101
  87.1%
Black or African American
0
   0.0%
1
  33.3%
2
  13.3%
0
   0.0%
6
   6.7%
9
   7.8%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
1
   0.9%
American Indian or Alaskan Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
1
   0.9%
Other
0
   0.0%
0
   0.0%
2
  13.3%
0
   0.0%
1
   1.1%
3
   2.6%
Unknown
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
1
   0.9%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 15 participants 6 participants 89 participants 116 participants
0 (Fully active)
1
  33.3%
2
  66.7%
6
  40.0%
3
  50.0%
39
  43.8%
51
  44.0%
1 (Restrictive but ambulatory)
2
  66.7%
1
  33.3%
9
  60.0%
3
  50.0%
50
  56.2%
65
  56.0%
[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; 5 = Dead.
1.Primary Outcome
Title Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
Hide Description

The MTD was defined as the highest carfilzomib dose at which < 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:

Nonhematologic:

  • ≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting < 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)
  • ≥ grade 3 acute kidney injury (creatinine > 3 x baseline or > 4.0 mg/dL) lasting > 72 hours
  • ≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy

Hematologic:

  • grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) for > 7 days
  • febrile neutropenia (ANC < 1000/mm³ with a fever ≥ 38.3ºC) of any duration
  • grade 4 thrombocytopenia (< 25 000/mm³) for > 14 days, despite holding treatment
  • grade 3 or 4 thrombocytopenia (< lower limit of normal) associated with > grade 1 bleeding
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in phase 1 who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).
Arm/Group Title Phase 1 Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed 3 3 15 6
Measure Type: Number
Unit of Measure: participants
0 0 1 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 1 Carfilzomib 45 mg/m², Phase 1: Carfilzomib 56 mg/m², Phase 1: Carfilzomib 70 mg/m², Phase 1: Carfilzomib 88 mg/m²
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Maximum Tolerated Dose (mg/m²)
Estimated Value 70
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description

Disease response was evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).

sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).

CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM.

VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.

PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.

Time Frame Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m² Phase 1+2: Carfilzomib 70 mg/m²
Hide Arm/Group Description:
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed 3 3 15 6 89 104
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(0.8 to 90.6)
100
(29.2 to 100.0)
93.3
(68.1 to 99.8)
66.7
(22.3 to 95.7)
74.2
(63.8 to 82.9)
76.9
(67.6 to 84.6)
3.Secondary Outcome
Title Clinical Benefit Response Rate
Hide Description Clinical benefit rate was defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a 25% to 49% reduction in the level of serum M-protein or a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour, maintained for a minimum of 8 weeks.
Time Frame Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m² Phase 1+2: Carfilzomib 70 mg/m²
Hide Arm/Group Description:
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed 3 3 15 6 89 104
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
66.7
(9.4 to 99.2)
100.0
(29.2 to 100.0)
100.0
(78.2 to 100.0)
83.3
(35.9 to 99.6)
80.9
(71.2 to 88.5)
83.7
(75.1 to 90.2)
4.Secondary Outcome
Title Progression-free Survival
Hide Description

Progression-free survival (PFS) was defined as the time from first dose to the earlier of disease progression or death due to any cause. The duration of PFS was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.

Participants were evaluated for disease response and progression by the investigator according to the IMWG-URC.

Time Frame From randomization until the data cut-off date of 22 July 2016; median follow-up time for PFS was 13.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m² Phase 1+2: Carfilzomib 70 mg/m²
Hide Arm/Group Description:
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed 3 3 15 6 89 104
Median (95% Confidence Interval)
Unit of Measure: months
13.6
(6.4 to 20.7)
NA [1] 
(41.7 to NA)
21.0 [1] 
(4.2 to NA)
12.9
(3.9 to 20.0)
15.3
(10.0 to 20.2)
16.2
(10.2 to 21.0)
[1]
Could not be estimated due to the low number of events
5.Secondary Outcome
Title Time To Progression
Hide Description Time to progression (TTP) was defined as the time from first dose to disease progression evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). TTP was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.
Time Frame From randomization until the data cut-off date of 22 July 2016; median follow-up time for TTP was 13.4 months
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Hide Analysis Population Description
Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m² Phase 1+2: Carfilzomib 70 mg/m²
Hide Arm/Group Description:
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed 3 3 15 6 89 104
Median (95% Confidence Interval)
Unit of Measure: months
13.6
(6.4 to 20.7)
NA [1] 
(41.7 to NA)
21.0 [1] 
(4.2 to NA)
12.9
(3.9 to 20.0)
16.2
(10.2 to 20.2)
17.2
(10.6 to 21.7)
[1]
Could not be estimated due to the low number of events
6.Secondary Outcome
Title Duration of Response
Hide Description Duration of response (DOR) was defined as the time from first evidence of PR or better to disease progression or death due to any cause. DOR was calculated using Kaplan-Meier methods; Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.
Time Frame From randomization until the data cut-off date of 22 July 2016; median follow-up time for DOR was 14.3 months
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Hide Analysis Population Description
Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone) with a best overall response of sCR, CR, VGPR, or PR.
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m² Phase 1+2: Carfilzomib 70 mg/m²
Hide Arm/Group Description:
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed 1 3 14 4 66 80
Median (95% Confidence Interval)
Unit of Measure: months
18.9 [1] 
(NA to NA)
NA [1] 
(39.9 to NA)
16.3 [1] 
(3.3 to NA)
11.9
(11.1 to 18.9)
18.0
(13.7 to 21.9)
18.0
(14.5 to 21.9)
[1]
Could not be estimated due to the low number of events
7.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Adverse events were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4.03).
Time Frame From the first day of study treatment and within 30 days of the last day of study treatment; median duration of treatment was 33.6 weeks.
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Hide Analysis Population Description
Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m²
Hide Arm/Group Description:
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed 3 3 15 6 89
Measure Type: Count of Participants
Unit of Measure: Participants
All adverse events
3
 100.0%
3
 100.0%
15
 100.0%
6
 100.0%
89
 100.0%
Adverse events ≥ grade 3
1
  33.3%
2
  66.7%
9
  60.0%
5
  83.3%
60
  67.4%
Serious adverse events
1
  33.3%
0
   0.0%
4
  26.7%
1
  16.7%
35
  39.3%
AE leading to discontinuation of carfilzomib & dex
0
   0.0%
0
   0.0%
2
  13.3%
3
  50.0%
14
  15.7%
AE leading to discontinuation of carfilzomib
0
   0.0%
0
   0.0%
2
  13.3%
3
  50.0%
14
  15.7%
Fatal adverse events
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5
   5.6%
8.Secondary Outcome
Title Time to Maximum Plasma Concentration of Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 26 21 5
Median (Full Range)
Unit of Measure: hours
0.25
(0.17 to 0.75)
0.25
(0.08 to 0.58)
0.25
(0.25 to 0.58)
9.Secondary Outcome
Title Maximum Plasma Concentration of Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 26 21 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
789
(65.5%)
2390
(30.7%)
3090
(27.3%)
10.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 26 21 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
281
(52.7%)
1040
(21.7%)
1210
(31.4%)
11.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 25 16 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
259
(28.0%)
1040
(21.6%)
1160
(34.8%)
12.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 25 16 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
259
(28.0%)
1040
(21.6%)
1160
(34.8%)
13.Secondary Outcome
Title Volume of Distribution Observed at Steady State (Vss) for Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 24 16 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters
17.0
(133.3%)
14.2
(54.2%)
7.87
(78.4%)
14.Secondary Outcome
Title Terminal Half-life (T1/2,z) for Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 25 15 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
0.648
(49%)
0.883
(24.6%)
0.816
(17.1%)
15.Secondary Outcome
Title Clearance of Carfilzomib After IV Infusion
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 25 16 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters/hour
147
(31.0%)
131
(29.6%)
138
(35.0%)
16.Secondary Outcome
Title Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.
Arm/Group Title Carfilzomib 20 mg/m² Carfilzomib 70 mg/m² Carfilzomib 88 mg/m²
Hide Arm/Group Description:
Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.
Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.
Overall Number of Participants Analyzed 24 16 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
0.118
(130.5%)
0.108
(55.4%)
0.0571
(110.0%)
Time Frame From the first day of study treatment and within 30 days of the last day of study treatment; median duration of treatment was 33.6 weeks.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m²
Hide Arm/Group Description Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
All-Cause Mortality
Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m²
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m²
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)   0/3 (0.00%)   4/15 (26.67%)   1/6 (16.67%)   35/89 (39.33%) 
Blood and lymphatic system disorders           
Anaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Febrile neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Thrombocytopenia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Cardiac disorders           
Acute myocardial infarction  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Atrial fibrillation  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Cardiac failure congestive  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  2/89 (2.25%) 
Cardio-respiratory arrest  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Sinus tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Gastrointestinal disorders           
Gastrointestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
General disorders           
Asthenia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Disease progression  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Pain  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Pyrexia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Infections and infestations           
Influenza  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Lung infection  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Pneumocystis jirovecii pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  4/89 (4.49%) 
Pneumonia influenzal  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Sepsis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  5/89 (5.62%) 
Septic shock  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Urinary tract infection  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Injury, poisoning and procedural complications           
Haematuria traumatic  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Hip fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Lumbar vertebral fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Investigations           
Blood creatinine increased  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Metabolism and nutrition disorders           
Hypercalcaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Hyperkalaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Hyponatraemia  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Metabolic acidosis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Back pain  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Musculoskeletal chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Pain in extremity  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Acute lymphocytic leukaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Prostate cancer  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Nervous system disorders           
Aphasia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Encephalopathy  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Hypertensive encephalopathy  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Ischaemic stroke  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Spinal cord compression  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Syncope  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Psychiatric disorders           
Delirium  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Renal and urinary disorders           
Acute kidney injury  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  6/89 (6.74%) 
Respiratory, thoracic and mediastinal disorders           
Acute respiratory distress syndrome  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Chronic obstructive pulmonary disease  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  3/89 (3.37%) 
Dyspnoea  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Hypoxia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Pneumonitis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Respiratory failure  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Vascular disorders           
Aortic dissection  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Deep vein thrombosis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1: Carfilzomib 45 mg/m² Phase 1: Carfilzomib 56 mg/m² Phase 1: Carfilzomib 70 mg/m² Phase 1: Carfilzomib 88 mg/m² Phase 2: Carfilzomib 70 mg/m²
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   3/3 (100.00%)   15/15 (100.00%)   6/6 (100.00%)   87/89 (97.75%) 
Blood and lymphatic system disorders           
Anaemia  1  1/3 (33.33%)  2/3 (66.67%)  5/15 (33.33%)  1/6 (16.67%)  25/89 (28.09%) 
Neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  8/89 (8.99%) 
Thrombocytopenia  1  0/3 (0.00%)  0/3 (0.00%)  3/15 (20.00%)  1/6 (16.67%)  22/89 (24.72%) 
Thrombocytosis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Cardiac disorders           
Arrhythmia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Palpitations  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  4/89 (4.49%) 
Tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  5/89 (5.62%) 
Congenital, familial and genetic disorders           
Porokeratosis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Eye disorders           
Amblyopia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Blindness  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Cataract  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  2/89 (2.25%) 
Conjunctival haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Dry eye  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  1/6 (16.67%)  1/89 (1.12%) 
Eye discharge  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Eye irritation  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Eye pruritus  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Glaucoma  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Periorbital oedema  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Photophobia  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Vision blurred  1  0/3 (0.00%)  2/3 (66.67%)  1/15 (6.67%)  2/6 (33.33%)  5/89 (5.62%) 
Visual acuity reduced  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Visual impairment  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Gastrointestinal disorders           
Abdominal discomfort  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  1/6 (16.67%)  4/89 (4.49%) 
Abdominal distension  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  3/89 (3.37%) 
Abdominal pain  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  8/89 (8.99%) 
Abdominal pain upper  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  0/89 (0.00%) 
Constipation  1  1/3 (33.33%)  1/3 (33.33%)  6/15 (40.00%)  1/6 (16.67%)  11/89 (12.36%) 
Diarrhoea  1  2/3 (66.67%)  0/3 (0.00%)  9/15 (60.00%)  2/6 (33.33%)  26/89 (29.21%) 
Dyspepsia  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  5/89 (5.62%) 
Epigastric discomfort  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Flatulence  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Gastrointestinal tract irritation  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Gastrooesophageal reflux disease  1  1/3 (33.33%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  3/89 (3.37%) 
Gingival pain  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Hypoaesthesia oral  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Loose tooth  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Nausea  1  0/3 (0.00%)  1/3 (33.33%)  7/15 (46.67%)  3/6 (50.00%)  36/89 (40.45%) 
Rectal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Sensitivity of teeth  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  1/89 (1.12%) 
Stomatitis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  3/89 (3.37%) 
Tooth loss  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Toothache  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Vomiting  1  0/3 (0.00%)  0/3 (0.00%)  4/15 (26.67%)  2/6 (33.33%)  13/89 (14.61%) 
General disorders           
Asthenia  1  0/3 (0.00%)  1/3 (33.33%)  4/15 (26.67%)  0/6 (0.00%)  9/89 (10.11%) 
Chest discomfort  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  3/89 (3.37%) 
Chills  1  0/3 (0.00%)  1/3 (33.33%)  4/15 (26.67%)  0/6 (0.00%)  5/89 (5.62%) 
Cyst  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Fatigue  1  3/3 (100.00%)  2/3 (66.67%)  9/15 (60.00%)  3/6 (50.00%)  47/89 (52.81%) 
Feeling hot  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Influenza like illness  1  1/3 (33.33%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  3/89 (3.37%) 
Infusion site extravasation  1  0/3 (0.00%)  0/3 (0.00%)  3/15 (20.00%)  0/6 (0.00%)  3/89 (3.37%) 
Infusion site pain  1  0/3 (0.00%)  1/3 (33.33%)  3/15 (20.00%)  1/6 (16.67%)  7/89 (7.87%) 
Malaise  1  0/3 (0.00%)  0/3 (0.00%)  4/15 (26.67%)  2/6 (33.33%)  5/89 (5.62%) 
Mucosal inflammation  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Oedema peripheral  1  0/3 (0.00%)  1/3 (33.33%)  4/15 (26.67%)  0/6 (0.00%)  20/89 (22.47%) 
Pain  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  1/6 (16.67%)  7/89 (7.87%) 
Peripheral swelling  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  4/89 (4.49%) 
Pyrexia  1  0/3 (0.00%)  0/3 (0.00%)  7/15 (46.67%)  3/6 (50.00%)  22/89 (24.72%) 
Sluggishness  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Submandibular mass  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Hepatobiliary disorders           
Cholelithiasis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Infections and infestations           
Bronchitis  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  0/6 (0.00%)  7/89 (7.87%) 
Cellulitis  1  0/3 (0.00%)  0/3 (0.00%)  3/15 (20.00%)  0/6 (0.00%)  3/89 (3.37%) 
Clostridium difficile infection  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Cystitis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Fungal skin infection  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Herpes zoster  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Influenza  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  3/89 (3.37%) 
Joint abscess  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Localised infection  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Lung infection  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Mycobacterium avium complex infection  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Nasopharyngitis  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  2/6 (33.33%)  9/89 (10.11%) 
Oral candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Oral herpes  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Paronychia  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  1/89 (1.12%) 
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  6/89 (6.74%) 
Sinusitis  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  8/89 (8.99%) 
Tinea pedis  1  0/3 (0.00%)  1/3 (33.33%)  3/15 (20.00%)  0/6 (0.00%)  0/89 (0.00%) 
Tinea versicolour  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Tooth abscess  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Tooth infection  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Upper respiratory tract infection  1  1/3 (33.33%)  2/3 (66.67%)  12/15 (80.00%)  2/6 (33.33%)  25/89 (28.09%) 
Urinary tract infection  1  1/3 (33.33%)  1/3 (33.33%)  2/15 (13.33%)  1/6 (16.67%)  10/89 (11.24%) 
Injury, poisoning and procedural complications           
Contusion  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  8/89 (8.99%) 
Facial bones fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Fall  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  2/89 (2.25%) 
Foot fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  1/89 (1.12%) 
Infusion related reaction  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Laceration  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  2/6 (33.33%)  0/89 (0.00%) 
Ligament sprain  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  2/6 (33.33%)  2/89 (2.25%) 
Post procedural complication  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Spinal compression fracture  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Aspartate aminotransferase increased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  2/89 (2.25%) 
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Blood creatinine increased  1  1/3 (33.33%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  13/89 (14.61%) 
Blood glucose increased  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Blood magnesium decreased  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Blood potassium decreased  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Blood pressure increased  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Blood sodium decreased  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Blood testosterone decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Blood urea increased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Cardiac murmur  1  0/3 (0.00%)  2/3 (66.67%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Haematocrit decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Heart rate increased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Neutrophil count increased  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Platelet count decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  7/89 (7.87%) 
Protein total decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Urine output decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Weight decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  4/89 (4.49%) 
Weight increased  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  1/6 (16.67%)  4/89 (4.49%) 
White blood cell count decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  3/89 (3.37%) 
White blood cell count increased  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  0/89 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite  1  0/3 (0.00%)  1/3 (33.33%)  2/15 (13.33%)  0/6 (0.00%)  13/89 (14.61%) 
Dehydration  1  1/3 (33.33%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  7/89 (7.87%) 
Fluid retention  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Hyperglycaemia  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  1/6 (16.67%)  8/89 (8.99%) 
Hyperkalaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  8/89 (8.99%) 
Hypokalaemia  1  1/3 (33.33%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  9/89 (10.11%) 
Hypophosphataemia  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  6/89 (6.74%) 
Iron deficiency  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Vitamin D deficiency  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  0/3 (0.00%)  2/3 (66.67%)  5/15 (33.33%)  0/6 (0.00%)  15/89 (16.85%) 
Arthritis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Back pain  1  2/3 (66.67%)  0/3 (0.00%)  5/15 (33.33%)  1/6 (16.67%)  18/89 (20.22%) 
Bone pain  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  3/89 (3.37%) 
Flank pain  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  4/89 (4.49%) 
Groin pain  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  2/89 (2.25%) 
Muscle spasms  1  0/3 (0.00%)  0/3 (0.00%)  6/15 (40.00%)  1/6 (16.67%)  10/89 (11.24%) 
Muscular weakness  1  0/3 (0.00%)  0/3 (0.00%)  5/15 (33.33%)  0/6 (0.00%)  12/89 (13.48%) 
Musculoskeletal chest pain  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  9/89 (10.11%) 
Musculoskeletal discomfort  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Musculoskeletal pain  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  6/89 (6.74%) 
Musculoskeletal stiffness  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Myalgia  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  0/6 (0.00%)  5/89 (5.62%) 
Myopathy  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Neck pain  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  3/89 (3.37%) 
Osteoarthritis  1  0/3 (0.00%)  2/3 (66.67%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Osteonecrosis of jaw  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  1/6 (16.67%)  1/89 (1.12%) 
Pain in extremity  1  0/3 (0.00%)  1/3 (33.33%)  4/15 (26.67%)  3/6 (50.00%)  14/89 (15.73%) 
Pain in jaw  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  0/89 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Basal cell carcinoma  1  1/3 (33.33%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  1/89 (1.12%) 
Benign neoplasm of skin  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Melanocytic naevus  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Squamous cell carcinoma  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Nervous system disorders           
Burning sensation  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Dizziness  1  1/3 (33.33%)  0/3 (0.00%)  5/15 (33.33%)  0/6 (0.00%)  14/89 (15.73%) 
Dizziness postural  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Dysgeusia  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  4/89 (4.49%) 
Facial paralysis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Headache  1  0/3 (0.00%)  2/3 (66.67%)  6/15 (40.00%)  4/6 (66.67%)  26/89 (29.21%) 
Hypoaesthesia  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Memory impairment  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  1/89 (1.12%) 
Migraine  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Neuropathy peripheral  1  0/3 (0.00%)  1/3 (33.33%)  4/15 (26.67%)  0/6 (0.00%)  6/89 (6.74%) 
Paraesthesia  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Peripheral sensory neuropathy  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  3/89 (3.37%) 
Psychomotor hyperactivity  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Spinal cord compression  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Visual field defect  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Psychiatric disorders           
Affective disorder  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Agitation  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  1/89 (1.12%) 
Anger  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  0/89 (0.00%) 
Anxiety  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  1/6 (16.67%)  11/89 (12.36%) 
Depression  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  1/6 (16.67%)  5/89 (5.62%) 
Insomnia  1  2/3 (66.67%)  2/3 (66.67%)  5/15 (33.33%)  3/6 (50.00%)  29/89 (32.58%) 
Irritability  1  1/3 (33.33%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  1/89 (1.12%) 
Mood altered  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Reproductive system and breast disorders           
Testicular pain  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Bradypnoea  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Cough  1  0/3 (0.00%)  0/3 (0.00%)  5/15 (33.33%)  2/6 (33.33%)  25/89 (28.09%) 
Dry throat  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Dysphonia  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  1/6 (16.67%)  1/89 (1.12%) 
Dyspnoea  1  1/3 (33.33%)  1/3 (33.33%)  5/15 (33.33%)  2/6 (33.33%)  25/89 (28.09%) 
Dyspnoea exertional  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  1/6 (16.67%)  3/89 (3.37%) 
Epistaxis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  5/89 (5.62%) 
Haemoptysis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Hiccups  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Hypoxia  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  0/6 (0.00%)  5/89 (5.62%) 
Nasal congestion  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  2/6 (33.33%)  2/89 (2.25%) 
Oropharyngeal pain  1  0/3 (0.00%)  0/3 (0.00%)  3/15 (20.00%)  2/6 (33.33%)  5/89 (5.62%) 
Pleural effusion  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Productive cough  1  0/3 (0.00%)  1/3 (33.33%)  1/15 (6.67%)  2/6 (33.33%)  7/89 (7.87%) 
Pulmonary congestion  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Rhinorrhoea  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Rhonchi  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Sinus congestion  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  6/89 (6.74%) 
Sputum discoloured  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  1/6 (16.67%)  0/89 (0.00%) 
Throat irritation  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  0/89 (0.00%) 
Upper-airway cough syndrome  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  2/89 (2.25%) 
Wheezing  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  3/89 (3.37%) 
Skin and subcutaneous tissue disorders           
Actinic keratosis  1  1/3 (33.33%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  3/89 (3.37%) 
Dermatitis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Dry skin  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  3/89 (3.37%) 
Ecchymosis  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  2/89 (2.25%) 
Erythema  1  0/3 (0.00%)  1/3 (33.33%)  0/15 (0.00%)  0/6 (0.00%)  1/89 (1.12%) 
Hyperhidrosis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  1/6 (16.67%)  3/89 (3.37%) 
Hyperkeratosis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Night sweats  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  2/89 (2.25%) 
Pruritus  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  7/89 (7.87%) 
Pruritus generalised  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Rash  1  0/3 (0.00%)  1/3 (33.33%)  3/15 (20.00%)  1/6 (16.67%)  13/89 (14.61%) 
Rash maculo-papular  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  4/89 (4.49%) 
Rash pruritic  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  3/89 (3.37%) 
Skin lesion  1  1/3 (33.33%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  2/89 (2.25%) 
Swelling face  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  1/89 (1.12%) 
Urticaria  1  0/3 (0.00%)  0/3 (0.00%)  0/15 (0.00%)  1/6 (16.67%)  2/89 (2.25%) 
Vascular disorders           
Hypertension  1  1/3 (33.33%)  0/3 (0.00%)  2/15 (13.33%)  2/6 (33.33%)  16/89 (17.98%) 
Hypotension  1  0/3 (0.00%)  0/3 (0.00%)  2/15 (13.33%)  0/6 (0.00%)  3/89 (3.37%) 
Phlebitis  1  0/3 (0.00%)  0/3 (0.00%)  1/15 (6.67%)  0/6 (0.00%)  1/89 (1.12%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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: NCT01677858    
Other Study ID Numbers: 2012-002
20130403 ( Other Identifier: Amgen Inc. )
First Submitted: August 30, 2012
First Posted: September 3, 2012
Results First Submitted: July 11, 2017
Results First Posted: August 9, 2017
Last Update Posted: December 19, 2018